WO2021203144A1

WO2021203144A1 - Multi-stage blood filtration

Info

Publication number: WO2021203144A1
Application number: PCT/US2021/070352
Authority: WO
Inventors: David Lerner; David J. HASKVITZ; Linda Lee HART
Original assignee: Nuwellis, Inc.
Priority date: 2020-04-02
Filing date: 2021-04-02
Publication date: 2021-10-07

Abstract

A blood filtration system may reduce one or more plasma constituents in blood of a patient. The system may include one or more filters. A first filter may provide a filtrate fluid including the first set of filtered plasma constituents to a second filter. The second filter may reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter. The system may include one or more pumps. For instance, a blood pump may pressurize flow of blood into the first filter at a first pressure. A filtration pump may extract the filtrate fluid from the first filter. The filtration pump may pressurize flow of the filtrate fluid into the second filter at a second pressure. The second pressure may be higher than the first pressure.

Description

MULTI-STAGE BLOOD FILTRATION

CLAIM OF PRIORITY

This patent application claims the benefit of priority of Lerner et al., U.S. Provisional Patent Application Serial Number 63/004,238, entitled “MULTI-STAGE BLOOD FILTRATION SYSTEM,” filed on April 2, 2020 (Attorney Docket No. 4567.034PRV), which is hereby incorporated by reference herein in its entirety.

TECHNICAL FIELD

This document pertains generally, but not by way of limitation, to a blood filtration system.

BACKGROUND

In an approach, a blood filtration system may include a filter. The filter may reduce one or more plasma constituents from blood flowing through the filter. In an approach, the filter may become occluded (e.g., clogged, blocked, or the like), for instance due to clotting of blood in the filter. For example, a first filter may become occluded, and the occlusion may degrade performance of the first filter. The clogging of the first filter may lead to replacement of the first filter with a second filter.

In another approach, a pump drives blood through components of the blood filtration system (including the filter). For instance, the pump may pressurize blood in a withdrawal line, and the pump may drive the blood through the filter. The system may limit pressure applied to the blood by the pump, for instance to protect cellular constituents of the blood (e.g., red blood cells, white blood cells, or the like).

SUMMARY

The present inventors have recognized, among other things, that a problem to be solved can include reducing one or more plasma constituents in blood of a patient. Additionally, the present inventors have recognized, among other things, that a problem to be solved can include increasing a rate of reducing the one or more plasma constituents from the blood of the patient. For example, a blood filtration system may include a blood circuit having a filter. The filter may reduce one or more plasma constituents (e.g., water, electrolytes, or the like) in the blood flowing through the filter. For instance, the filter may provide a filtrate fluid including plasma constituents removed from the blood. In an example, the filter may remove water from blood, and the filter may provide a filtrate fluid including the water removed from the blood.

One or more pumps may drive fluid through the blood filtration system. For instance, a blood pump may drive blood through the filter. In another example, a filtration pump may facilitate removal of the filtrate fluid (including one or more plasma constituents) from the filter. For instance, the filtration pump may drive filtrate fluid from the filter.

The one or more pumps may apply pressure to fluid (e.g., blood, filtrate fluid, water, or the like) in the filter. For example, the blood pump may pressurize blood to drive the blood through the filter (and provide a filtrate fluid). The flow rate of filtrate fluid provided by the filter may correspond with the pressure applied by the pump. In an example, the blood pump may pressurize blood in the filter at a first filter pressure. The filter may provide the filtrate fluid at a first flow rate with the blood pressurized at the first filter pressure. The blood pump may pressurize blood in the filter at a second filter pressure. The filter may provide the filtrate fluid at a second flow rate with the blood pressurized at the second filter pressure. Accordingly, changes in pressure applied by the pump may correspondingly change the flow rate of filtrate fluid provided by the filter. Thus, the one or more pumps may be operated to vary fluid flow rates through the blood filtration system.

The pressure applied to the blood in the blood circuit may be limited, for instance to protect cellular constituents of the blood (e.g., red blood cells, white blood cells, or the like). In an approach, pressure applied to the blood may damage the cellular constituents of the blood (e.g., hemolyze, damage to a cellular membrane, or the like). For instance, blood pressurized in excess of a specified threshold may rupture red blood cells in the blood. Accordingly, the blood filtration system may limit pressure applied to fluid in the blood circuit (including the filter) to protect cellular constituents of the blood.

As described herein, the rate of reduction of plasma constituents from blood with the filter may correspond with the pressure applied to blood in the filter. Accordingly, the limiting of pressure applied to the blood may correspondingly limit the flow rate of filtrate fluid provided by the filter. Thus, limits on pressure applied to blood in the filter may correspondingly limit the rate of removal of plasma constituents by the filter. The present subject matter can help provide a solution to these problems, such as by increasing rate of removal of plasma constituents by a filter for a blood filtration system. Additionally, the present subject matter can help provide a solution to these problems, such as with a blood filtration system including one or more filters. For example, the blood filtration system may include a first filter having a first filter membrane. The first filter may reduce an amount of a first set of plasma constituents in blood flowing through the first filter.

The first filter may provide a filtrate fluid including the first set of filtered plasma constituents. For instance, the first filter membrane may allow water to pass to a filtrate fluid port. Accordingly, the first filter may reduce the amount of water in blood flowing through the first filter. The first filter may provide a return fluid, and the return fluid may be infused back into the patient. The return fluid may include a second set of plasma constituents. For instance, the first filter membrane may inhibit one or more of red blood cells, white blood cells, platelets, or the like from passing to the filtrate fluid port. The first filter may allow the red blood cells to pass to a filter outlet. Thus, the first filter may selectively filter constituents of blood flowing through the first filter and provide one or more of a filtrate fluid (including a first set of plasma constituents) or a return fluid (including a second set of plasma constituents).

In an example, the blood filtration system may help separate cellular constituents of blood (e.g., red blood cells, white blood cells, or the like) from non-cellular constituents of blood (e.g., water, proteins such as one or more of albumin or cytokine, electrolytes, viruses, bacteria, or the like). For instance, the first filter may receive blood and the remove a first set of plasma constituents (e.g., non-cellular plasma constituents such as water, or the like) from the blood. In an example, the first filter separates the first set of plasma constituents from a second set of plasma constituents (e.g., cellular plasma constituents, such as red blood cells, or the like).

The blood filtration system may include a second filter having a second filter membrane. The second filter may be in communication with the first filter. For instance, the second filter may receive the filtrate fluid provided by the first filter. In an example, the second filter may reduce an amount of plasma constituents in the filtrate fluid provided by the first filter. In an example, the second filter may reduce a third set of plasma constituents from the filtrate fluid provided by the first filter. In another example, the filtrate fluid (with the reduced amount the third set of plasma constituents) may be infused back into the patient. For example, the first set of plasma constituents (e.g., proteins such as albumin, water, electrolytes, or the like) may be transmitted to the second filter. The second filter may remove a third set of plasma constituents (e.g., water, or the like) from the first set of plasma constituents. In an example, the first set of plasma constituents (without the third set of plasma constituents) may be infused back into the patient from the second filter.

The blood filtration system may include a blood circuit that transmits fluids (e.g., blood, or the like) through the blood filtration system. In an example, the blood circuit includes a catheter, and the catheter may facilitate withdrawal of blood from (or infusion of blood into) vasculature of a patient. The blood circuit may include a withdrawal line, and the withdrawal line may be in communication with the catheter. The withdrawal line may be in communication with one or more filters, for instance the first filter. Accordingly, blood may flow from the catheter, through the withdrawal line, and into the filter. The blood circuit may include an infusion line, and the infusion line may be in communication with the one or more filters. For instance, the infusion line may receive blood from the filter (e.g., the filter may provide filtered blood to the infusion line, or the like).

The blood filtration system may include one or more adjustable pumps, for instance an adjustable blood pump that facilitates transmission of blood through the blood circuit. For instance, the pumps are adjustable to change one or more of pressure or flow rate of fluids driven (e.g., pumped, pushed, pulled, forced, or the like) by the pump. Accordingly, the pump may be adjusted (e.g., a controller may modulate the pump, or the like) to correspondingly adjust one or more of pressure or flow rate of fluid in the blood circuit.

The one or more pumps of the blood filtration system may include a filtration pump that facilitates transmission of fluid in the blood circuit. For instance, a filtrate line may be in communication between the first filter and the second filter. The first filter may provide the filtrate fluid to the filtrate line. The filtration pump may facilitate removal of filtrate fluid from the first filter. The filtration pump may be in communication with one or more of the first filter or the filtrate line. The filtration pump may pressurize flow of the filtrate fluid, for instance by driving the filtrate fluid into the second filter.

The filtration pump may cooperate with the blood pump to remove plasma constituents from blood flowing through the filter. For instance, the blood pump may supply positive pressure to a blood inlet port of the first filter. The filtration pump may supply negative pressure to a filtrate port of the first filter. The first filter membrane may separate the blood inlet port from the filtrate port. The first filter membrane may selectively allow the flow of one or more plasma constituents across the first filter membrane from the blood inlet port to the filtrate port. The positive pressure provided by the blood pump may cooperate with the negative pressure provided by the filtration pump to generate a pressure differential across the first filter membrane. Accordingly, the one or more pumps may cooperate with the filter to remove plasma constituents from blood (or other fluids) flowing through the filter.

As described herein, the pumps may pressurize fluid flowing through the blood circuit. For instance, the blood pump may pressurize blood flowing through the first filter at a first pressure. The filtration pump may pressurize filtrate fluid flowing through the second filter at a second pressure. The second pressure may be different than (e.g., higher than, lower than, or the like) the first pressure. Accordingly, the filtrate fluid flowing through the second filter may be subjected to different pressure than the blood flowing through the first filter. Variations in pressure applied to fluid flowing through the one or more filters may correspondingly vary flow rates through the one or more filters.

The blood filtration system may enhance removal of one or more plasma constituents from blood of a patient. For example, the one or filters and the one or more pumps may cooperate to increase the rate that one or more plasma constituents are removed from blood of a patient. As described herein, the one or more filters may separate cellular constituents of blood from non-cellular constituents of blood. The blood pump may pressurize the blood flowing through the first filter at a first pressure. For instance, the system may limit the first pressure to refrain from exceeding a specified pressure threshold. In some approaches, subjecting blood to pressure exceeding the specified pressure threshold may damage one or more constituents of the blood (e.g., rupturing of red blood cells, or the like). Accordingly, the system may limit the first pressure to refrain from exceeding the specified pressure threshold to protect the cellular constituents of blood.

The limiting of pressure applied to blood may correspondingly limit the rate of removing constituents (e.g., water, or the like) from the blood. For instance, the system may have a first filtration rate of removing plasma constituents from blood with the blood pump operating at the first pressure. The system may have a second filtration rate of removing plasma constituents from blood with the blood pump operating at the second pressure. An (absolute) increase pressure applied to fluid flowing through the filter may correspondingly increase the rate that plasma constituents are removed by the filter. An (absolute) decrease in pressure applied to fluid flowing through the filter may corresponding decrease the rate that plasma constituents are removed by the filter. Thus, limiting pressure applied to blood (or other fluid) flowing through a filter may correspondingly limit the rate of removal of plasma constituents with the filter.

As described herein, the first filter may facilitate separation of cellular plasma constituents from non-cellular plasma constituents. The separation of cellular constituents from non-cellular constituents of blood may facilitate an increase in a rate of removal of plasma constituents from the blood. For example, the system may subject the filtrate fluid (including non-cellular constituents of blood) to a pressure exceeding the specified pressure threshold (where cellular constituents may be damaged) because the first filter separates the cellular constituents from filtrate fluid (including the non-cellular constituents of blood). In an example, the pressure applied to the filtrate fluid may exceed the specified pressure threshold because the filtrate fluid includes non-cellular constituents of blood (and the specified pressure threshold is associated with cellular constituents of blood). Accordingly, the system may increase the rate of removal of plasma constituents from the blood of the patient because the filtrate fluid is subjected to pressures exceeding the specified pressure threshold (and correspondingly increases filtration rates with the one or more filters). Thus, separating cellular and non-cellular constituents of blood enhances performance of the blood filtration system, for example by enhancing the rate of removing water (or other plasma constituents) from blood of a patient.

This overview is intended to provide an overview of subject matter of the present patent application. It is not intended to provide an exclusive or exhaustive explanation of the invention. The detailed description is included to provide further information about the present patent application.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings, which are not necessarily drawn to scale, like numerals may describe similar components in different views. Like numerals having different letter suffixes may represent different instances of similar components. The drawings illustrate generally, by way of example, but not by way of limitation, various embodiments discussed in the present document.

Figure 1 illustrates a schematic view of an example of portions of a blood filtration system, according to an embodiment of the present subject matter.

Figure 2 illustrates a schematic view of another example of portions of the blood filtration system of Figure 1, according to an embodiment of the present subject matter.

Figure 3 illustrates a schematic view of yet another example of portions of the blood filtration system of Figure 1, according to an embodiment of the present subject matter.

Figure 4 illustrates a schematic view of a still yet another example of portions of the blood filtration system of Figure 1, according to an embodiment of the present subject matter.

Figure 5 illustrates a cross-sectional view of an example of a hollow fiber for a filter membrane.

Figure 6 illustrates a side view of the hollow fiber of Figure 5. Figure 7 illustrates a schematic view of an additional example of portions of the blood filtration system of Figure 1, according to an embodiment of the present subject matter.

Figure 8 illustrates a schematic view of still yet another example of portions of the blood filtration system, according to an embodiment of the present subject matter.

Figure 9 illustrates a block diagram of an example machine upon which any one or more of the techniques discussed herein may perform Figure 10 illustrates one example of a method for reducing an amount of plasma constituents in blood of a patient, including one or more of the blood filtration system described herein. DETAILED DESCRIPTION

Figure 1 illustrates a schematic view of an example of portions of a blood filtration system 100, according to an embodiment of the present subject matter. The blood filtration system 100 may reduce one or more plasma constituents (e.g., water, proteins, electrolytes, or the like) in blood of a patient. The blood filtration system 100 may facilitate one or more blood filtration operations, including (but not limited to): extracorporeal ultrafiltration, continuing renal replacement therapy (“CRRT”), slow continuous ultrafiltration (“SCUF”), continuous veno-venous hemofiltration (“CVVH”), continuous veno-venous hemofiltration (“CVVHD”), dialysis, continuous veno-venous hemofiltration including dialysis and filtration (“CVVHDF”), sustained low efficiency dialysis (“SLED”), extracorporeal membrane oxygenation (“ECMO”) therapy, modified ultrafiltration, and peripheral plasmapheresis, peripheral hemofiltration.

The blood filtration system 100 may include a controller 102. The controller 102 may include processing circuitry, for instance an integrated circuit or the like. As described herein, the controller 102 may be configured to control one or more components, functions, features, operations, or the like of the blood filtration system 100.

The blood filtration system 100 may include a withdrawal line 104 and may include an infusion line 106. The lines 104, 106 may be configured to couple with a catheter 108, and the lines 104, 106 may transmit blood within the blood filtration system 100. In an example, the catheter 108 may be inserted into a blood stream of the patient, for instance the catheter 108 may be inserted into a basilic vein, cephalic vein, brachial vein, the axillary vein, the subclavian vein, the brachiocephalic vein, or the like. Blood may flow into the catheter 108, into the withdrawal line 104, through other components of the system 100, through the infusion line 106, into the catheter 108, and back into the blood stream of the patient. The line 104 may be separate from the line 106. The lines 104, 106 may be in communication with the catheter 108. For example, the catheter 108 may include one or more lumens, for example a withdrawal lumen in communication with the line 104 and an infusion lumen in communication with the line 106.

The lines 104, 106 may be configured to couple with a filter 110, for instance the lines 104, 106 may include one or more fittings that facilitate coupling the lines 104, 106 with the filter 110. In an example, the withdrawal line 104 may couple with a filter inlet port 111 A, and the infusion line 106 may couple with a filter outlet port 11 IB. The filter 110 may be configured to reduce an amount of one or more plasma constituents (e.g., water, electrolytes, or the like) in blood flowing through the filter 110 and provide a filtrate fluid including the one or more plasma constituents. As described herein, blood may flow through the lines 104, 106 to and from the catheter 108. The lines 104, 106 may be coupled with the filter and blood may flow from the withdrawal line 104, through the filter 110, and into the infusion line 106.

The blood filtration system 100 may include a blood pump 112, and the blood pump 112 may pump (e.g., convey, drive, push, or the like) blood through the blood filtration system 100. In an example, the blood pump 112 may be a peristaltic pump, and the blood pump 112 may engage with the withdrawal line 104 to pump blood through the withdrawal line 104 and into the filter 110. The controller 102 may be configured to operate the blood pump 112 to vary a speed of the blood pump 112 and accordingly vary the flow rate of blood through the blood filtration system 100 (e.g., the withdrawal line 104, the filter 110, the infusion line 106, or the like).

Referring again to Figure 1, the blood filtration system 100 may include a filtration line 114 and a filtration pump 116. The filtration line 114 may be configured to couple with the filter 110 (e.g., with a fitting), for instance the filtration line 114 may couple with a filtrate fluid port 111C. The filter 110 may be configured to transmit the filtrate fluid (including one or more plasma constituents) extracted by the filter 110 to the filtrate fluid port lllC.

The filtration pump 116 may pump extracted filtrate fluid from the filter 110, and into a filtrate fluid reservoir 118 (e.g., a bag, container, bladder, or the like). In some examples, the filtration pump 116 may be a peristaltic pump that engages with the filtration line 114 to pump the filtrate fluid through the filtrate fluid line 114. The controller 102 may be configured to vary a speed of the filtration pump 116 and accordingly vary the flow rate of filtrate fluid through the blood filtration system 100 (e.g., the filtration line 114). In an example, the controller 102 may be configured to control the speed of the blood pump 112 and set the flow rate of blood through the filter 110 at a first blood flow rate. Additionally, the controller 102 may be configured to control the speed of the blood pump 112 and set the flow rate of blood through the filter at a second blood flow rate. The first blood flow rate may be different than the second blood flow rate. The system 100 may include a blood circuit 120, and the blood circuit 120 may include one or more components of the system 100, such as may provide a conduit for blood flow. For example, the blood circuit 120 may include (but is not limited to) the withdrawal line 104, the infusion line 106, the catheter 108, the filter 110, the filtration line 114, the filtrate fluid reservoir 118. The blood circuit 120 may include components of the system 100 that are in communication with a biological fluid of the patient.

In some examples, the blood filtration system 100 may include one or more access ports 122, for instance a first access port 122 A, a second access port 122B, and a third access port 122C. The access ports 122 may facilitate the extraction of blood from the blood filtration system 100, or injection of substances (e.g., imaging substance, a blood thinner, for instance heparin or the like) into the blood within the blood filtration system 100. In an example, the access ports 122 A, 122B may be in communication with the withdrawal line 104, and the access port 122C may be in communication with the infusion line 106.

A valve 124 (e.g., a mechanical check valve, or electronically controlled valve) may be positioned between the access ports 122 A, 122B, and the valve 124 may be configured to allow blood to flow unidirectionally within the withdrawal line 104 (e.g., flowing from the catheter 108 to the filter 110). In this example, a substance may be injected into the withdrawal line 104 at the access port 122B, and blood may be withdrawn from the access port 122 A. Because the valve 124 facilitates unidirectional flow within the withdrawal line 104, the blood including the substance will not be withdrawn from the access port 122A, for instance because the access port 122A is upstream of the access port 120B). In an example, heparin may be infused into the access port 122B and blood is drawn from the access port 122A to measure blood clotting time parameters of a patient. Because the blood is drawn from the access port 122 A, the withdrawn blood does not include heparin, and in an example, a blood clotting time parameter determination is not affected by the heparin injection at the access port 122B. Accordingly, the performance of blood filtration system 100 is thereby improved.

As shown in Figure 1, the blood filtration system 100 may include one or more sensors 126 (e.g., transducer, accelerometer, or the like), for instance a first sensor 126A, a second sensor 126B, and a third sensor 126C. The first sensor 126A may measure (e.g., obtain, provide, quantify, evaluate, or the like) the pressure within the withdrawal line 104, the second sensor 126B may measure the pressure within the infusion line 106, and the third sensor 126C may measure the pressure within the filtration line 114. The sensors 126 may include a fourth sensor 126D (e.g., a position sensor, or the like) and a fifth sensor 126E (e.g., blood flow rate, or the like), and the sensor 126E may determine the blood flow rate through the system 100 (e.g., a component of the blood circuit 120, for example the withdrawal line 104).

Figure 2 illustrates a schematic view of another example of portions of the blood filtration system 100, according to an embodiment of the present subject matter. The blood filtration system 100 may include one or more filters 200, for instance a first filter 202. The first filter may include one or more of a first inlet port 204, a first filtrate port 206, or a first return port 208. The first filter 202 may receive blood at the inlet port 204. The filter 202 may help reduce an amount of plasma constituents in the blood. For instance, the first filter 202 may provide a filtrate fluid at the filtrate port 206. The first filter 202 may provide a return fluid at the return port 208.

In an example, a first filter membrane 210 may help reduce plasma constituents in blood flowing through the first filter 202. For instance, the first filter 202 may separate a first set of plasma constituents (e.g., non-cellular constituents of blood such as water, or the like) from a second set of plasma constituents (e.g., cellular plasma constituents, such as red blood cells, or the like). For instance, the first filter membrane 210 may allow the first set of plasma constituents to flow across the first filter membrane 210. The first filter membrane 210 may inhibit the second set of plasma constituents from flowing across the first filter membrane 210. In another example, the first set of plasma constituents may flow across the first filter membrane 210 to provide a filtrate fluid. For instance, the first filter 202 may provide a filtrate fluid (including the first set of plasma constituents) at the filtrate port 206. The filter 202 may provide a return fluid (including the second set of plasma constituents) at the return port 208. The return fluid may include blood with the reduced amount of the first set of plasma constituents (e.g., removal of filtrate fluid may reduce an amount of the first set of plasma constituents in the blood, or the like). Accordingly, the first filter 202 may help reduce an amount (e.g., a mass, volume, concentration, or the like) of plasma constituents (e.g., the first set of constituents) from blood, for example by separating the first set of plasma constituents from the second set of plasma constituents.

The blood filtration system 100 may include a second filter 212. The second filter 212 may include one or more of a second inlet port 214, a second filtrate port 216, or a second return port 218. The second filter 212 may be in communication with the first filter 202. In an example, the second filter 212 may receive filtrate fluid from the first filter 202. For instance, a filtrate line 220 (e.g., tubing, piping, conduits, or the like) may extend between the first filter 202 and the second filter 212. For instance, the filtrate line 220 may transmit filtrate fluid from the filtrate port 206 of the first filter to the inlet port 204 of the second filter 212.

The second filter 212 may reduce plasma constituents in the filtrate fluid provided by the first filter 202. For example, the first filter 202 may provide the filtrate fluid (including the first set of plasma constituents) to the second filter 212. The second filter 212 may separate a third set of plasma constituents from the first set of plasma constituents (included in the filtrate fluid). In an example, a second filter membrane 222 may help reduce plasma constituents in fluid (e.g., filtrate fluid, blood, effluent, or the like) flowing through the second filter 212. Accordingly, the second filter 212 may help separate the first set of plasma constituents (e.g., one or more of proteins, water, electrolyte, cytokines, or the like) into a third set of plasma constituents (e.g., water, electrolytes, cytokines, or the like) and a fourth set of plasma constituents (e.g., water, electrolytes, or the like).

For instance, the second filter membrane 222 may allow the third set of plasma constituents to flow across the second filter membrane 222. The second filter membrane 222 may inhibit the fourth set of plasma constituents from flowing across the membrane 222. Thus, the second filter 212 may reduce plasma constituents in the filtrate fluid provided by the first filter 202.

The second filter 212 may provide a filtrate fluid (including the third set of plasma constituents) at the second filtrate port 216. The second filter 212 may provide a return fluid (including the fourth set of plasma constituents) at the second return port 218. The return fluid of the second filter 212 may include the filtrate fluid (provided by the first filter 202) with a reduced amount of the third set of plasma constituents. Accordingly, the second filter 212 may help reduce an amount (e.g., a mass, volume, concentration, or the like) of plasma constituents (e.g., the third set of constituents) from the filtrate fluid provided by the first filter 202, for example by separating the first set of plasma constituents into a third set of plasma constituents and a fourth set of plasma constituents. Thus, the first filter 202 may provide a first filtrate fluid including the first set of plasma constituents, and the second filter 212 may provide a second filtrate fluid including the third set of plasma constituents. The second filter 212 may provide the second filtrate fluid to a container, for instance a filtrate container 224. For instance, the filtrate container 224 may communicate with the second filtrate port 216 of the second filter 212. The filtrate container 224 may facilitate collection of the second filtrate fluid, for example to allow disposal of the filtrate fluid.

The first filter 202 and the second filter 212 may communicate with a fluid combiner 226. The fluid combiner 226 may combine fluids received from the first filter 202 and the second filter 212, for example to facilitate infusion of the fluid into vasculature of the patient. For instance, the fluid combiner 226 may communicate with the infusion line 106. In another example, a first return line 228 may extend between the first filter 202 and the fluid combiner 226. For instance, the first return line 228 may communicate with the first return port 208 of the first filter 202. Accordingly, the first return line 228 may receive the return fluid (including the second set of plasma constituents such as red blood cells, or the like) from the first filter 202. The blood filtration system 100 may include a second return line 230 extending between the second filter 212 and the fluid combiner 226. For example, the second return line 230 may communicate with the second return port 218 of the second filter 212. Thus, the second return line 230 may receive the return fluid (including the fourth set of plasma constituents such as proteins, or the like) from the second filter 212. Accordingly, the fluid combiner 226 may receive fluid from the first and second filters 202, 212 and combine the fluids for infusion into vasculature of the patient. For example, the fluid combiner 226 may communicate with the infusion line 106 to infuse fluid into the vasculature of the patient.

The blood filtration system 100 may include one or more pumps 232, and the one or more pumps 232 may drive fluid through the blood filtration system 100. For instance, the blood pump 112 may drive blood through the first filter 202 or the second filter 212. In an example, the blood pump 112 drives blood from the withdrawal line 104 to the first filter 202. In another example, the blood pump 112 drives blood through the first filter 202 and to the fluid combiner 226. In yet another example, the filtration pump 116 may facilitate removal of filtrate fluid (including one or more plasma constituents) from the one or more filters 200.

For instance, the filtration pump 116 may drive filtrate fluid from the first filter 202 to the second filter 212.

The one or more pumps 232 may apply pressure to fluid (e.g., blood, filtrate fluid, water, or the like) in the blood circuit 120. The pumps 232 may apply pressure to the fluid. For example, the blood pump 112 may pressurize blood to drive the blood through the one or more of the filters 200 (and provide a filtrate fluid). The flow rate of filtrate fluid provided by a filter (e.g., the first filter 202, or the likeO may correspond with the pressure applied by the pumps 232. In an example, the blood pump 112 may pressurize blood in the first filter 202 at a first filter pressure. The first filter 202 may provide the filtrate fluid at a first flow rate with the blood pressurized at the first filter pressure by the blood pump 112. The blood pump 112 may pressurize blood in the filter at a second filter pressure. The first filter 202 may provide the filtrate fluid at a second flow rate with the blood pressurized at the second filter pressure. Accordingly, changes in pressure applied by the blood pump 112 may correspondingly change the flow rate of filtrate fluid provided by the first filter 202. Thus, the one or more pumps 232 may be operated to vary fluid flow rates through the blood filtration system 100.

In an example, the one or more pumps 232 include a peristaltic pump. In another example, the blood filtration system may include one or more solenoid valves that generate a pressure gradient across one or more filter membrane. In an example, the blood pump 112 may drive blood through the first filter 202. The filtrate pump 116 may extract filtrate fluid from the first filter 202. A return pump may facilitate flow through the first filter, for example by generating a negative pressure on the return port 208 (shown in Figure 2) of the first filter 202

In another example, the system 100 may passively transmit fluid in the blood circuit 120. For example, the system may passively transmit filtrate fluid to the second filter 212 passively. In yet another example, the blood pump 112 may generate a transmural pressure created to pump blood through the first filter 202 and provide a filtrate fluid. Accordingly, in some examples, the system 100 transmits filtrate fluid to the second filter 212 without the filtrate pump 116. In still yet another example, the system 100 may passively transmit (e.g., due to transmural pressure created in the second filter 212) filtrate fluid to a container, such as the filtrate container 224 shown in Figure 2.

The pressure applied to the blood in the blood circuit 120 may be limited, for instance to protect cellular constituents of the blood (e.g., red blood cells, white blood cells, or the like). In an approach, pressure applied to the blood may damage the cellular constituents of the blood (e.g., hemolysis, damage to a cellular membrane, or the like). For instance, blood pressurized in excess of a specified pressure threshold may rupture cellular constituents of blood including (but not limited to) red blood cells. Accordingly, the blood filtration system may limit pressure applied to fluid in the blood circuit 120 (including the first filter 202, or the like) to protect cellular constituents of the blood. In an example, the pumps 232 are adjustable to change one or more of pressure or flow rate of fluids driven (e.g., pumped, pushed, pulled, forced, or the like) by the pumps 232. Accordingly, the pumps 232 may be adjusted (e.g., the controller 102, shown in Figure 1, may modulate the pumps 232, or the like) to correspondingly adjust one or more of pressure or flow rate of fluid in the blood circuit 120.

The one or more pumps 232 of the blood filtration system 100 may include the filtration pump 116 that facilitates transmission of filtrate fluid in the blood circuit 120. For instance, the filtrate line 220 may extend between the first filter 202 and the second filter 212. The first filter 202 may provide filtrate fluid to the filtrate line 220 (e.g., the filtrate port 206 may discharge filtrate fluid to the filtrate line 220, or the like). The filtration pump 116 may facilitate removal of filtrate fluid from the first filter 202. In an example, the filtration pump 116 may be in communication with one or more of the first filter 202 or the filtrate line 220. The filtration pump 116 may pressurize flow of the filtrate fluid, for instance by driving the filtrate fluid into the second filter 212. In another example, the filtrate pump 116 is a first filtrate pump 116, and the pumps 232 include a second filtrate pump 234. The second filtrate pump 234 may facilitate transmission of filtrate fluid from the second filter 212 (e.g., transmission to the collection container 224, or the like). Accordingly, the pumps 232 help transmit fluids through the blood filtration system 100.

The filtration pump 116 may cooperate with the blood pump 112 to reduce plasma constituents in blood flowing through the first filter 202. For instance, the blood pump 112 may supply positive pressure to the inlet port 204 of the first filter 202. The filtration pump 116 may supply negative pressure to the filtrate port 206 of the first filter 202. The first filter membrane 210 may separate the blood inlet port 204 from the filtrate port 206. The first filter membrane 210 may selectively allow the flow of one or more plasma constituents across the first filter membrane 210 from the inlet port 204 to the filtrate port 206. The positive pressure provided by the blood pump 112 may cooperate with the negative pressure provided by the filtration pump 116 to generate a pressure differential across the first filter membrane 210. For instance, the pumps 112, 116 may cooperate to create a transmural pressure across the first filter membrane 210. Accordingly, the one or more pumps 232 may cooperate with the filters 200 to reduce plasma constituents in blood (or other fluids) flowing through the filters 200. As described herein, the pumps 232 may pressurize fluid flowing through the blood circuit 120. For instance, the blood pump 112 may pressurize blood flowing through the first filter 202 at a first pressure. The filtration pump 116 may pressurize filtrate fluid flowing through the second filter 212 at a second pressure. The second pressure may be different than (e.g., higher than, lower than, or the like) the first pressure. Accordingly, the filtrate fluid flowing through the second filter 212 may be subjected to different pressure than the blood flowing through the first filter 202. Variations in pressure applied to fluid flowing through the one or more filters 200 may correspondingly vary flow rates through the one or more filters 200.

The blood filtration system 100 may enhance reduction of one or more plasma constituents in blood of a patient. For example, the one or filters 200 and the one or more pumps 232 may cooperate to increase the rate that one or more plasma constituents are removed from blood of a patient. As described herein, the one or more filters 200 may separate cellular constituents of blood from non-cellular constituents of blood. The blood pump 112 may pressurize the blood flowing through the first filter 202 at a first pressure. For instance, the system 100 may limit the first pressure to refrain from exceeding a specified pressure threshold. In some approaches, subjecting blood to pressure exceeding the specified pressure threshold may damage one or more constituents of the blood (e.g., rupturing of red blood cells, or the like). Accordingly, the system 100 may limit the first pressure to refrain from exceeding the specified pressure threshold to protect the cellular constituents of blood.

The limiting of pressure applied to blood may correspondingly limit the rate of reducing constituents (e.g., water, or the like) in the blood. For instance, the system 100 may have a first filtration rate of reducing plasma constituents from blood with the blood pump 112 operating at the first pressure. The system may have a second filtration rate of reducing plasma constituents from blood with the blood pump 112 operating at the second pressure.

An (absolute) increase pressure applied to fluid flowing through the filter may correspondingly increase the rate that plasma constituents are reduced by the first filter 202. An (absolute) decrease in pressure applied to fluid flowing through the first filter 202 may corresponding decrease the rate that plasma constituents are reduced by the first filter 202. Thus, limiting pressure applied to blood (or other fluid) flowing through a filter may correspondingly limit the rate of reduction of plasma constituents with the filter. As described herein, the first filter 202 may facilitate separation of cellular plasma constituents from non-cellular plasma constituents. The separation of cellular constituents from non-cellular constituents of blood may facilitate an increase in a rate of reduction of plasma constituents from the blood. For example, the system 100 may subject the filtrate fluid (including non-cellular constituents of blood) to a pressure exceeding the specified pressure threshold (where cellular constituents may be damaged) because the first filter 202 separates the cellular constituents from filtrate fluid (including the non-cellular constituents of blood). In an example, the pressure applied to the filtrate fluid (e.g., filtrate fluid in the filtrate line 220, or the like) may exceed the specified pressure threshold because the filtrate fluid includes non-cellular constituents of blood (and the specified pressure threshold is associated with cellular constituents of blood). Accordingly, the system 100 may increase the rate of reduction of plasma constituents from the blood of the patient because the filtrate fluid is subjected to pressures exceeding the specified pressure threshold (and correspondingly increases filtration rates with the one or more filters 200). Thus, separating cellular and non- cellular constituents of blood enhances performance of the blood filtration system 100, for example by enhancing the rate of reducing water (or other plasma constituents) in blood of a patient.

Figure 3 illustrates a schematic view of yet another example of portions of the blood filtration system 100, according to an embodiment of the present subject matter. As described herein, the system 100 may include the one or more filters 200. For instance, the system may include the first filter 202, the second filter, and a third filter 300. The first filter 202 may provide a first filtrate fluid (e.g., including the first set of plasma constituents, or the like) to the second filter 212. The second filter 212 may provide a third filtrate fluid to the third filter 300.

In an example, the second filter 212 may separate the first filtrate fluid into a third set of plasma constituents and a fourth set of plasma constituents. The second filter 212 may provide a second filtrate fluid at the second filtrate port 216. The second filter 212 may provide a second return fluid (including the fourth set of plasma constituents) to the fluid combiner 226.

The blood filtration system 100 may include the blood circuit 120 having the filtrate line 220, and the filtrate line 220 may be a first filtrate line 220. The first filtrate line 220 may extend between the first filter 202 and the second filter 212. The blood filtration system 100 may include a second filtrate line 310, and the second filtrate line 310 may extend between the second filter 212 and the third filter 300. For instance, the filtrate line 310 may communicate with the second filtrate port 216. Accordingly, the second filter 212 may provide the second filtrate fluid (including the third set of plasma constituents) to the third filter 300. For example, the second filtrate pump 234 may drive the second filtrate fluid in the filtrate line 310 to the third filter 300. Thus, the one or more filters 200 may help the system 100 filter blood (or filter constituents of blood).

The third filter 300 may separate constituents of the second filtrate fluid provided by the second filter 212. For instance, the second filtrate fluid may include the third set of plasma constituents. The third filter 300 may separate the third set of plasma constituents into a fifth set of plasma constituents and a sixth set of plasma constituents. In an example, the third filter 300 includes a third filter membrane 312. For instance, the third filter membrane 312 may allow the fifth set of plasma constituents to flow across the third filter membrane 312. The third filter membrane 312 may inhibit the sixth set of plasma constituents from flowing across the third filter membrane 312. Accordingly, the third filter 300 may provide a third filtrate fluid (including the fifth set of plasma constituents, or the like) at a third filtrate port 304. In another example, the third filter 300 may provide a fourth filtrate fluid (including the sixth set of plasma constituents, or the like). Thus, the third filter 300 may reduce plasma constituents in the second filtrate fluid provided by the second filter 212.

The third filter 300 may provide the filtrate fluids to one or more container (or to the fluid combiner 226). For example, a first filtrate container 314 may communicate with the third filtrate port 304. Accordingly, the first filtrate container 314 may receive the third filtrate fluid (including the fifth set of plasma constituents, or the like). In another example, a second filtrate container 316 may communicate with the fourth filtrate port 306. Thus, the second filtrate container 314 may receive the fourth filtrate fluid (including the sixth set of plasma constituents, or the like). As a result, the filtrate containers 314, 316 may facilitate collection of the second filtrate fluid, for example to allow disposal of the filtrate fluid. In yet another example, one or more of the port 304 or the port 306 of the third filter 300 may communicate with a fluid combiner, for instance the fluid combiner 226.

Figure 4 illustrates a schematic view of still yet another example of portions of the blood filtration system 100, according to an embodiment of the present subject matter. The blood filtration system 100 may include one or more fluid switches 400, and the fluid switches 400 may facilitate transmission of fluid in the blood circuit 120. For instance, the fluid switches 400 may help change between the one or more filters 200 of the system 100. Accordingly, a user (e.g., a healthcare provider, or the like) can customize which filter (or filters) are used during therapy with the blood filtration system 100.

The blood circuit 120 may include lines to transmit blood, such as the withdrawal line 104 and the infusion line 106. In another example, the blood circuit 120 may include one or more routing lines 402. The switches 400 may cooperate with the routing lines 402 to transmit fluid between components of the blood circuit 120. In an example, the one or more fluid switches 400 include a first fluid switch 404. The first fluid switch 404 may route fluid (e.g., blood, filtrate fluid, or the like) through the one or more filters 200. For instance, the blood filtration system 100 may include a first filter 406 and a second filter 408. The first fluid switch 404 may route fluid between the first filter 406 or the second filter 408. For example, the switch 404 may receive blood from the withdrawal line 104 and selectively route the blood to the first filter 406 or the second filter 408. In another example, the first filter 406 may include a first inlet port 410. The second filter 408 may include a second inlet port 412. In yet another example, the first fluid switch 404 may selectively route the blood to the first inlet port 410 of the first filter 406. In still yet another example, the first fluid switch 404 may selectively route the blood to the second inlet port of the second filter 408. In a still yet further example, a controller (e.g., the controller 102, shown in Figure 1, or the like) may modulate the switch 400 to change between the first filter 406 and the second filter 408.

Referring to Figure 4, the first filter 406 may include a first filtrate port 414. The first filter 406 may receive blood from the switch 404, and the first filter 406 may provide a first filtrate fluid (including a first set of plasma constituents) at the first filtrate port 414. The second filter 408 may include a second filtrate port 416. The second filter 408 may receive blood from the switch 404, and the second filter 408 may provide a second filtrate fluid (including a second set of plasma constituents) at the second filtrate port 416. Accordingly, the system 100 may selectively provide the first filtrate fluid with the first filter 406, or selectively provide the second filtrate fluid with the second filter 408. In another example, the switch 404 may allow blood to flow to both the first filter 406 and the second filter 408.

The blood filtration system 100 may transmit the filtrate fluid of the first filter 406 or the second filter 408 to additional filters of the one or more filters 200. In an example, the one or more filters 200 may include a third filter 418 or a fourth filter 420. In another example, at least one of the third filter 418 or the fourth filter 420 communicate with one or more of the first filter 406 or the second filter 408. For example, the third filter 418 may receive the first filtrate fluid from the first filter 406. The third filter 418 may receive the second filtrate fluid from the second filter 408. Accordingly, the blood circuit 120 and the switches 400 may cooperate to help transmit fluid (e.g., blood, filtrate fluid, water, electrolytes, or the like) through the filters 200 of the blood filtration system 100.

In an example, the selective routing provided by the switches 400 routes the filtrate fluid of the first filter to the third filter 418. For instance, the blood filtration system 100 may include a first fluid combiner 424. The fluid combiner 424 may receive filtrate fluid from one or more of the first filtrate port 414 or the second filtrate port 416. The fluid combiner 424 may include one or more one-way valves that inhibit flow between the first filtrate port 414 or the second filtrate port 416. Accordingly, the fluid combiner 424 may facilitate transmission of filtrate fluid to other components of the blood circuit 120, including (but not limited to) the third filter 418 or the fourth filter 420.

Referring to Figure 4, and as described herein, the blood filtration system 100 may include fluid switches 400 that facilitate selective routing of fluid in the blood circuit 120.

The first fluid combiner 424 may receive filtrate fluid from one or more of the first filter 406 or the second filter 408. The fluid combiner 424 may provide the filtrate fluid provided by one or more of the first filter 406 or the second filter 408 to a second fluid switch 426.

In an example, the second fluid switch 426 may selectively route the filtrate fluid received from the fluid combiner 424 to one or more of the third filter 418 or the fourth filter 420. For instance, the second fluid switch 426 may communicate with a third inlet port 428 of the third filter 418. The second fluid switch 426 may communicate with a fourth inlet port 430 of the fourth filter 420. Accordingly, the second fluid switch 426 may help transmit filtrate fluid between the one or more filters 200 of the blood filtration system 100.

As described herein, and in an example, the filters 200 of the blood filtration system 100 may separate plasma constituents of blood into different sets of plasma constituents. For example, the third filter 418 may receive the filtrate fluid from the second fluid switch 426, and the third filter 418 may provide a third filtrate fluid at a third filtrate port 432. The fourth filter 420 may receive the filtrate fluid from the second fluid switch 426, and the fourth filter 420 may provide a fourth filtrate fluid at a fourth filtrate port 434. Accordingly, the switch 400 may help selectively provide filtrate fluid with one or more of the third filter 418 or the fourth filter 420.

In another example, the third filter 418 and the fourth filter 420 may communicate with a third fluid combiner 436. For instance, the third filtrate port 432 may communicate with the fluid combiner 436. The fourth filtrate port 434 may communicate with the fluid combiner 436. Accordingly, the fluid combiner 436 may help transmit one or more of the third filtrate fluid or the fourth filtrate fluid to other components of the blood filtration system 100

For example, the third fluid combiner 436 may communicate with a fifth filter 438, and the third fluid combiner 436 may transmit filtrate fluid to the fifth filter 438. In yet another example, the fluid combiner 436 may receive filtrate fluid from one or more of the third filter 418 or the fourth filter 420. The fluid combiner 436 may transmit the filtrate fluid to a fifth inlet port 440 of the fifth filter 438. The filter 438 may separate plasma constituents of the filtrate fluid received at the inlet port 440. Accordingly, the fifth filter 438 may provide a fifth filtrate fluid (including a fifth set of plasma constituents). In an example, the fifth filtrate fluid includes water (or other plasma constituents) removed from blood transmitted through the withdrawal line 104. The fifth filtrate fluid (e.g., water, or the like) may collect in the filtrate container 224, for instance to facilitate disposal of the fifth filtrate fluid. Thus, the blood filtration system 100 may help reduce an amount of plasma constituents (e.g., water) in blood of a patient.

Referring to Figure 4, and as described herein, the filters 200 may communicate with a fluid combiner, for instance the first fluid combiner 424. In an example, the first filter includes a first return port 442. The first filter 406 may provide the first filtrate fluid (e.g., non-cellular plasma constituents, or the like) at the first filtrate port 414. The first filter 406 may provide a first return fluid (e.g., cellular plasma constituents, or the like) at the first return port. Accordingly, the first filter may separate blood into one or more sets of plasma constituents.

One or more of the first filter 406 or the second filter 408 may communicate with a fourth fluid combiner 446. In an example, the second filter 408 may include a second return port 444. One or more of the first return port 442 of the first filter 406 or the second return port 444 may provide return fluid to the fluid combiner 446. For instance, the second filter 212 may separate cellular constituents of blood from non-cellular constituents of blood. The second filter may include the cellular plasma constituents in a return fluid. The return fluid provided by the second filter may flow to the fluid combiner 446. The fluid combiner 446 may communicate with the infusion line 106, and accordingly the cellular plasma constituents may be infused into vasculature of the patient (without being included in a filtrate fluid provided by the second filter 408).

In another example, one or more of the third filter 418 or the fourth filter 420 may communicate with a fifth fluid combiner 448. The fifth fluid combiner 448 may receive return fluid provided by one or more of the third filter 418 or the fourth filter 420. In yet another example, the fifth fluid combiner 448 may communicate with the fourth fluid combiner 446, for instance to transmit return fluid from the third filter 418 (or the fourth filter 420) to the infusion line 106. In still yet another example, the fifth filter may provide a return fluid to the fourth fluid combiner 446.

The present inventors have realized, among other things, that a problem to be solved may include removing plasma constituents with an intermediate molecular weight. For example, separation of cytokines and albumin from other plasma constituents may be difficult due to similarities in molecular weight between cytokines and albumin. The blood filtration system may filter plasma constituents with a similar (e.g., intermediate, or the like) molecular weight. For instance, the filters 200 (e.g., the second filter 212 shown in Figure 3, or the like) may inhibit flow of albumin across the second filter membrane, and allow cytokines to flow across the second filter membrane 222. In another example, the third filter membrane 312 may inhibit flow of cytokines across the third filter membrane 312. The third filter membrane 312 may allow water to flow across the third filter membrane 312.

In yet another example, substances with a high molecular weight (e.g., cellular plasma constituents, such as red blood cells or the like) may be allowed to pass through a filter (and be reintroduced into vasculature of a patient). Substances with a low molecular weight (e.g., non-cellular plasma constituents, such as water, or the like) may be removed by the one or more filters 200 (shown, for example, in Figure 2). In an example, smaller constituents of blood may pass easily through a filter (e.g., the first filter 202, shown in Figure 2). Intermediate sized constituents may partially pass through the filter. Larger constituents may not pass through the filter. In some examples, the larger constituents will remain in the blood and infused back into the patient. As described herein, the molecular weight of a first constituent of blood (e.g., cytokines, or the like) may be similar to other non-cellular constituents of blood, for instance a second constituent of blood (e.g. albumin, or the like). In an example, system 100 may be configured to remove the first constituent from the blood without removing the second constituent of the blood. In another example, the molecular weight of cytokines and albumin may be intermediate between the molecular weight of red blood cells and water. For instance, the cytokine IL-6 has a molecular weight of approximately 21,000 daltons. The molecular weight of IL-6 is intermediate between the molecular weight of constituents that are to be retained such as albumin (molecular weight 65,000 daltons) and constituents that may be removed from the blood, such as water (molecular weight 18 daltons). The filter membrane 222 of the second filter 212 may have a filter pore size of approximately 50,000 to 70,000 daltons. Accordingly, IL-6 may be partially cleared with the second filter 212.

In another example, the second filter 212 may not remove plasma constituents with molecular weights over, for example 65,000 daltons (e.g., plasma proteins and red blood cells). The second filter 212 may remove smaller plasma constituents, such as water (e.g., 18 daltons, or the like) and sodium (e.g., 23 daltons). In an example, a molecule that is 21,000 daltons (e.g., cytokines implicated in septic shock, or the like) may be partially filtered, for instance because the molecule is intermediate in size (or mass) between 65,000 daltons (e.g., albumin) and 18 daltons (e.g., water). In yet another example, cellular constituents of blood (e.g., red blood cells, or the like) may be too large to pass through a filter membrane (e.g., the first filter membrane 210 shown in Figure 2, or the like) of the filter. Accordingly, the filter may help separate constituents of blood having intermediate molecular weights (or intermediate sizes).

In an example, and referring to Figure 2, the blood filtration system 100 may transmit blood to the first filter 202. The first filter 202 may include the first filter membrane 210. The first filter membrane 210 may a first pore size (e.g., 800,000 daltons, 400,000 daltons, 325,000 daltons, 100,000 daltons, less than 8 micrometers, less than 6 nanometers, or the like). The first filter 202 may communicate with the second filter 212. For instance, the first filter may provide filtrate fluid to the second filter. The second filter 212 may include the second filter membrane 222. The second filter membrane 222 may have a second pore size (e.g., 65,000 daltons, 5 micrometers, 3 nanometers, or the like). The second pore size of the second filter membrane 222 may be smaller than the first pore size of the first filter membrane 210.

In some examples, the filter membrane of the filters 200 may separate one or more plasma constituents based on a molecular weight of the plasma constituents. For example, the first filter membrane 210 may inhibit flow across the first filter membrane of molecules within a first range, for instance 85,000 daltons to approximately 115,000 daltons. The second filter membrane 222 may inhibit flow across the second filter membrane 222 of molecules within a second range, for instance 50,000 daltons to approximately 80,000 daltons. Accordingly, the second filter 212 may remove constituents having a smaller size than the constituents removed by the first filter 202. In an example, the first filter 202 may be a hemofiltration filter (e.g. including polysulfone, or the like). The second filter 212 may be a hemofilter. The second filter 212 may have a smaller molecular weight cutoff than the first filter 202.

The pore sizes, pore ranges, or the like provided herein are examples, and a person having ordinary skill in the art will appreciate that the first range or the second range may vary from the values described herein. The first range may overlap with the second range. In yet another example, the filter membrane may separate one or more plasma constituents based on size (e.g., occupied volume, dimensions, or the like) of the plasma constituents. Accordingly, units of measurement for defining the filter membrane of the filters 200 may vary from those described herein. The third filter membrane 312 (shown in Figure 3) of the third filter 300 may include a third pore size (e.g., 5,000 daltons, or the like). The third pore size may be smaller than one or more of the first pore size of the first filter membrane 210 or second pore size of the second filter membrane 222. Further, a person having ordinary skill in the art will appreciate that, in some examples, characteristics of a filter membrane are not consistent. In an example, a diameter of pores in hollow fibers of the filter membrane are not identical. For instance, there may be a gaussian distribution of pore diameters around a centroid value.

Figures 5 and 6 illustrate cross-sectional and side views (respectively) of an example of a hollow fiber 500 for a filter membrane (e.g., the first filter membrane 210). In an example, a filter membrane of the filters 200 may inhibit cellular constituents of blood from flowing through a pore 502 of the hollow fiber 500. The pore 502 may extend through a wall 504 of the hollow fiber 500. The hollow fiber 500 may include a plurality of pores 506, including the pore 502. Accordingly, the cellular constituents may pass through the filter. For instance, the cellular constituents may flow along a longitudinal axis 600 of the fiber to a return port of the filter (e.g., the return port 208, shown in Figure 2). Thus, the filter may not remove cellular constituents of blood from the blood in the filter. In some examples, albumin may not be removed from the blood (or filtrate fluid) by the filter. For example, albumin may facilitate maintenance of oncotic pressure in blood. Accordingly, the filters 200 may inhibit one or more non-cellular constituents from passing across the filter membrane. Thus, the blood filtration system 100 may reintroduce cellular plasma constituents (or non-cellular plasma constituents) back into vasculature of the patient.

A filter, for instance the first filter 202 may include one or more of the hollow fiber 500. The fiber 500 and the pores 506 may cooperate to help separate plasma constituents of blood. For example, the pores 506 may facilitate removal of plasma constituents from blood, for example when the plasma constituents flow through the pores 506. Accordingly, blood may flow through the hollow fibers, and the plasma constituents may flow across the filter membrane when the plasma constituents flow through the pores.

The one or more filters 200 (shown in Figure 2) may include an anticoagulant (e.g., heparin, or the like) coating, for instance a heparin coating coupled with one or more of the first filter membrane 210 or the second filter membrane 222. In an example, the anti coagulant coating may be coupled to the hollow fiber 500. The anti -coagulant coating may help minimize clotting of the filters 200, for example clotting due to sepsis, cytokine storm, or the like. Reducing clotting in the filter may enhance a lifetime of the filter, for example by increasing a length of time that the filter may be used to reduce an amount of plasma constituents in blood of a patient.

Referring to Figure 2, the blood filtration system 100 may help reduce the amount of plasma constituents in blood of a patient. In an example, the blood filtration system 100 may help remove plasma constituents with intermediate molecular weight from blood of a patient. For example, intermediate molecular weight blood constituents may include (but are not limited to) cytokines, such as interleukin 6 (“IL-6”). Cytokines are a large group of proteins that are secreted by specific cells of an immune system. The cytokines are a category of signaling molecules that, for example, mediate and regulate immunity, inflammation and hematopoiesis. Cytokines can be beneficial or deleterious to patient health. In an example, cytokines may trigger a beneficial inflammatory response, for instance to promote coagulation to confine tissue damage. In some examples, the blood filtration system 100 may not completely remove the cytokines from blood of a patient, for instance because cytokines may play a positive role in the immune or inflammatory response systems. Accordingly, the blood filtration system may control blood levels of one or more plasma constituents of blood of a patient (e.g., cytokines, water, or the like).

In another example, COVID-19 infection may cause one or more health issues for a patient. For instance, the virus may infect the lower respiratory tract, which may cause pulmonary injury through viral replication. The infection may lead to viral pneumonia and pneumonitis. The virus can also be detected in the bloodstream. The virus may cause one or more of cardiac injury, liver injury, or other organ injury. In another example, as seen in influenza, other coronavirus infections (e.g. SARS, MERS, and the like), and now COVID-19 infection, is the development of a cytokine storm. The cytokine storm may drive a severe systemic inflammatory response syndrome (SIRS), capillary leak syndrome, organ injury, or other complications.

In yet another example, sepsis may include as an unbalanced immune response of an organism to an infection, which may injure organs or tissues of a patient. In severe sepsis, excessive production of proinflammatory cytokines may cause capillary leakage, tissue injury, lethal organ failure, or the like. In another approach, cytokines may cause cytokine storm syndrome (e.g., excessive or uncontrolled release of proinflammatory cytokines, or the like). Because cytokines may facilitate coagulation, an increase in cytokines may lead to an increase in clotting of a filter. The cytokine Interleukin 6 (IL-6) may contribute to the negative consequences of coronavirus disease 2019 (e.g., COVID-19), or the like. However, other cytokines may contribute to negative consequences of COVID-19.

In an example, patients with COVID-19 may have an increased concentration of one or more cytokines. Accordingly, removal of plasma constituents (e.g., IL-6, other cytokines, or the like) from blood of the patient may enhance patient health and may reduce negative consequences of COVID-19. In some approaches, cytokine inhibitors (e.g., Ticlizumab, Sarilumab, Anakinara, or the like) may be used to mitigate effects of cytokines on a patient. However, in some approaches, cytokine inhibitors may cause undesirable side effects. Thus, the blood filtration system 100 may remove plasma constituents (e.g., cytokines) to mitigate the effects of cytokines on a patient, without usage of a cytokine inhibitors. For example, the blood filtration system 100 may reduce an amount of constituents in blood having intermediate molecular weight.

In an example, and referring to Figure 2, the first filter 202 may provide a filtrate fluid including the first set of plasma constituents. The first filter 202 may provide a return fluid that does not include the filtrate fluid (or the first set of plasma constituents, or a portion of the first set of plasma constituents). In an example, the return fluid may include cellular constituents of blood such as red blood cells, or the like. The return fluid may include water, and the filtrate fluid may include water. The return fluid may be returned to vasculature of a patient (e.g., by infusing the return fluid into a vein of a patient (e.g., with the catheter 108, shown in Figure 1, or the like). Accordingly, the one or more filters 200 may help selectively remove one or more plasma constituents from blood.

In another example, the filters 200 may remove a portion of water included in blood of a patient. In an example, the filters 200 may remove a first portion (e.g., 20 percent) of water in the blood. The filters 200 may provide a filtrate fluid (e.g., at the filtrate port 216, shown in Figure 2, or the like) that includes the first portion of water. The filters 200 may provide a return fluid (e.g., at one or more of the return ports 208 or return port 218, shown in Figure 2) that includes the second portion of water. The second portion of water may be reintroduced into the circulatory system of a patient. Accordingly, the filters 200 may reduce plasma constituents in blood of a patient.

Referring to Figure 2, the second filter 212 may reduce plasma constituents (e.g., a third set of plasma constituents) in the filtrate fluid provided by the first filter 202. For example, the second filter 212 may remove water, electrolytes, and cytokines from the filtrate fluid provided by the first filter 202. In an example, the second filter 212 may not remove albumin from the filtrate fluid provided by the first filter 202. For instance, albumin may facilitate maintenance of oncotic pressure in blood. Thus, the second filter 212 may provide a return fluid including (but not limited to) albumin. In an example, the albumin may be returned to vasculature of the patient. Accordingly, the blood filtration system 100 may remove one or more sets of plasma constituents (e.g., the first set and third set of plasma constituents, or the like). In yet another example, the blood filtration system 100 may return one or more sets of plasma constituents (e.g., the second set and fourth set of plasma constituents, or the like) to the vasculature of a patient. As described herein, the one or more filters 200 may help separate blood (or other fluid) into a first set of plasma constituents and a second set of plasma constituents. For instance, the first filter 202 may help remove water, electrolytes (e.g., sodium, or the like), cytokines, albumin, or the like from blood of a patient. In an example, the first filter 202 may reduce a portion of the first set of plasma constituents from the blood. For example, an amount of the first set of plasma constituents that are reduced by the filter 202 may be based on one or more of blood flow rate through the filter 202, filtration rate, hematocrit, sieving coefficient of the first set of plasma constituents with respect to the filter membrane, or the like.

In an example, the filtration rate and the associated reduction (e.g., removal, clearance, extraction, or the like) of plasma constituents from blood may be proportional to a surface area of the filter membrane and the transmembrane pressure. In another example, the filtration rate and associated removal of blood constituents may be inversely proportional to the hollow fiber wall thickness (e.g., a length of the pores, or the like). The filtration rate and associate reduction of blood constituents may correspond to a sieving coefficient of the plasma constituent (or blood constituent) of interest for a filter membrane. The sieving coefficient (e.g., a percentage, value, or the like) may be related to a reflection coefficient. For example, the sieving coefficient plus the reflection coefficient may equal 100% (e.g., RC + SC = 100%, or the like). For small molecules (small relative to the pore size), the reflection coefficient is approximately zero, and the sieving coefficient is approximately 100%. For large molecules (large relative to the pore size), the reflection coefficient is approximately 100% and the sieving coefficient is approximately 0%.

In some examples, the blood filtration system 100 may provide a sieving coefficient near 0% for plasma constituents that are sought to be retained in blood of a patient. For example, the blood filtration system may facilitate a sieving coefficient near zero for cellular plasma constituents including (but not limited to) red blood cells, plasma proteins (e.g., albumin), or the like. The blood filtration system may facilitate a sieving coefficient near 100% for plasma constituents that are sought to be removed from blood of a patient such as urea, toxins, or the like. For instance, the pore size of a filter (e.g., as measured by the molecular weight of constituents, or the like) may be approximately 50,000 to approximately 70,000 daltons. In this example, albumin may remain in the blood (e.g., because the sieving coefficient for albumin is 0%, or the like) and water may be removed by the filter (e.g., because the sieving coefficient for water is 100%, or the like). Thus, the filter membrane (e.g., pores of the filter membrane, or the like) may inhibit larger structures (e.g. red blood cells and plasma proteins) from flowing through the filter membrane. The larger structures may be blocked and remain in the filter membrane. The filter membrane may allow smaller structures (e.g. electrolytes and water) to flow across the filter membrane (e.g., by flowing through pores in a hollow fiber, or the like), for example for collection in a reservoir (or additional filtration, for instance by the third filter 300 shown in Figure 3, or the like).

As described herein, separation of plasma constituents may include driving (e.g., convective driving, or the like) of blood (or other fluids) by a pressure gradient developed across a filter membrane. For example, a blood pump may pump blood into a filter (e.g., blood may flow longitudinally through the filter). The blood pump may force blood through the filter membrane (e.g., hollow fibers, or the like). The blood pump may create transmural (e.g., transverse, transmembrane, or the like) pressure, and the transmural pressure may be normal to the direction of blood flow (e.g., normal to the longitudinal flow through the filter).

As described herein, the blood pump may generate a transmural pressure, and the transmural pressure may force molecules through a filter membrane. For instance, the blood pump may generate a positive pressure on a first side of the filter membrane. A filtration pump may generate a negative pressure, for example on a second side of the filter membrane. The filtration pump may be in fluidic communication with the tube, and the filtration pump may facilitate removal (e.g., extraction, evacuation, transmission, or the like) of filtrate fluid from the filter. The blood pump and the filtration pump may cooperate, for example to enhance a total pressure gradient across the filter membrane (e.g., a transmembrane pressure, or the like). Accordingly, flow across the filter membrane may be optimized to create a fluid flow and convection current for enhancing reduction of small structures in blood of a patient (e.g., to remove the small structures from the blood, or the like).

The blood filtration system 100 may enhance removal of plasma constituents from blood (e.g., cytokines, or the like) from blood of a patient, for instance by raising a filtration pressure (e.g., a pressure differential between a first side of the filter membrane and a second side of the filter membrane, a transmembrane pressure, or the like). In some approaches, increasing the filtration pressure may damage cellular constituents of blood such as red blood cells or the like. For instance, the increase in filtration pressure may induce a shear force (or other forces) upon the cellular constituents, and the shear force may damage the cellular constituents of blood. In an example, a pressure within a range of approximately -600 mmHg to approximately +1 000 mmHg may minimize damage to cellular constituents of blood.

In another approach, incomplete blood mixing may lead to a saturation of the filtration rate versus transmembrane pressure relationship (e.g., the filtration rate may not increase when the transmembrane pressure is increased beyond a pressure threshold value, or the like). For instance, where the pressure is raised beyond the pressure threshold value, the filtration rate will stop increasing. Accordingly, the filtration rate may saturate at higher pressure values. In another approach, saturation of the filtration rate may occur when red blood cells migrate near hollow fiber lumen walls and cause obstruction of pores of a filter. Obstruction of the pores (e.g., fouling, or the like) may lead to a saturation of the filtration rate versus transmembrane pressure relationship. In yet another approach, obstruction of a lumen (e.g., clotting, or the like) may lead to a saturation of the filtration rate versus transmembrane pressure relationship. Accordingly, a filtration rate of the system 100 may be limited when the transmembrane pressure exceeds a specified pressure threshold.

Referring to Figure 2, and in an example, the first filter 202 and the second filter 212 may cooperate to enhance the reduction of one or more plasma constituents in blood of a patient. For instance, the rate of reducing plasma constituents (e.g., water) in the blood may be enhanced because the first filter 202 inhibits flow of cellular constituents of blood into the filtrate fluid provided by the first filter 202. In another example, the cellular constituents of blood may not flow through (e.g., engage with, communicate with, interface with, interact with, or the like) the second filter 212. Accordingly, the cellular constituents of blood may not obstruct the second filter membrane 222 of the second filter 212. Thus, a pressure applied to fluid (or rate of flow) in the second filter 212 can be increased (without damaging cellular constituents of blood, or the like).

In another example, pressure applied to the filtrate fluid in the second filter 212 filter may not damage cellular constituents of blood (because the filtrate fluid does not include cellular constituents of blood). In yet another example, the pressure (or rate of filtration) of the second filter 212 can be increased, for instance because red blood cells are not present in the filtrate fluid that flows into the second filter. The increase in filtration pressure (or filtration rate) may enhance removal of the plasma constituents, for example by reducing an amount of time to remove the plasma constituents from blood. In still yet another example, the increase in filtration pressure (or filtration rate) may enhance removal of the plasma constituents, for example by reducing an amount of time to reduce a concentration of the plasma constituents in blood.

For example, the blood filtration system may provide a pathway for non-cellular components of blood, for example to minimize obstruction of one or more filter membranes of the filters 200. Accordingly, the blood filtration system 100 may minimize saturation of the filtration rate at higher transmembrane pressures values. Thus, the blood filtration system 100 may enhance removal of one or more plasma constituents, for instance by increasing a rate of removal of water from blood of a patient.

Referring to Figure 2, the blood filtration system 100 may include the one or more sensors 126. The sensors 126 may measure one or more properties of fluid in the blood filtration system. For example, the sensors may measure pressure, temperature, flow rate, plasma constituent concentration, hematocrit, or the like of fluid flowing through the blood circuit 120.

In an example, the blood filtration system 100 may include a fluid characteristic sensor 236 (e.g., an optical sensor, spectroscopy sensor, or the like) The fluid characteristic sensor 236 may measure characteristics of fluid in the blood circuit 120. For example, the sensor 236 may help detect the presence of plasma constituents in blood of a patient. In another example, the sensor 236 may help determine a concentration of plasma constituents in blood of a patient. For example, the sensor 236 may measure cytokines on the blood to inform (e.g., with a closed loop feedback system, or the like) the clearance rate of the cytokines and a therapy cessation point. In another example, the sensor 236 is an optical sensor, and the cytokine IL-6 has a response between 3 pm to 7pm. The optical sensor 236 may help measure the concentration of IL-6, for example by measuring optical properties (e.g., intensity of light within a spectrum of light) of fluid in the blood circuit 120.

The blood filtration system 100 may help measure the presence (or concentration) of the one or more plasma constituents in blood of a patient. For example, the blood filtration system may measure a concentration of cytokines in blood of a patient. In an example, the blood filtration system may include ELISA testing or other optical-based measurement of the plasma constituents. The concentration of plasma constituents in the blood (or filtrate fluid) may be challenging to measure (or detect). For example, detection of cytokines may be challenging because the concentration of the plasma constituents may be low. The blood filtration system 100 may help concentrate plasma constituents of blood in the blood circuit 120 to facilitate measurement of the plasma constituents. For example, the blood filtration system may provide a concentrate at the port 306 of the third filter 300. Accordingly, the system 100 may concentrate cytokines and provide the concentrate to a container, such as filtrate container 316. Accordingly, the system may facilitate measurement of plasma constituents (e.g., cytokines).

The sensors 126 may include a hematocrit sensor, such as an emitter-sensor pair embedded in a hematocrit cuvette or other optical aperture in the blood circuit 120. In an example, the hematocrit sensor may help maintain hemodynamic stability of blood in the blood circuit 120. For example, the system 100 may monitor hematocrit values of blood in the blood circuit to monitor hemo-concentration of the blood. In an example, the system 100 may monitor hematocrit to maintain hemo-concentration at a specified value. Accordingly, performance of the system 100 may be enhanced, for instance because the system 100 minimizes clotting in the filters 200 due to hemo-concentration.

In another example, the sensors 126 include a blood leak detector. For example, the blood leak detector may monitor the blood circuit 120 for leaks. In yet another example, the sensors 126 may monitor filtrate fluid provided by the filters 200. In still yet another example, the sensors 126 may monitor return fluid provided by the filters 200. Accordingly, the system 100 may monitor the blood circuit 120 for leaks. In another example, the sensors 126 including a blood leak detector may help determine if cellular plasma constituents are damaged. For instance, the sensors 126 may include a heme sensor configured to measure the concentration of a heme molecule in fluid in the blood circuit 120. Accordingly, the sensors 126 help the sensor protect cellular constituents of blood.

The blood filtration system 100 may include an optical window, for example to facilitate exposure of blood to a light emitting element (e.g., an LED included in the sensor 236, or the like). Exposing blood to the light emitting element may degrade one or more plasma constituents (e.g., cytokines, or the like). Accordingly, the system 100 may degrade the plasma constituents to help reduce an amount of the plasma constituents in blood of a patient.

In another example, the blood filtration system 100 may provide a notification (e.g., on a display, or the like) of a clearance rate corresponding to a rate of reduction (e.g., clearance, removal, or the like) of plasma constituents (e.g., water, cytokines, or the like) from blood of a patient. For instance, the blood filtration system 100 may include the controller 102. The controller 102 may determine the clearance rate a based on one or more of flow rate of the blood pump 112, a sieving coefficient of one or more of the filters 200, a filtration rate (e.g., flow rate of the filtrate pump 116, or the like), or an infusion rate of an infusion fluid.

Figure 7 illustrates a schematic view of an additional example of portions of the blood filtration system 100, according to an embodiment of the present subject matter. In an example, the blood filtration system 100 may provide an infusion fluid to the blood circuit 120. For instance, the one or more pumps 232 may include an infusion pump 700. The infusion pump 700 may drive an infusion fluid (e.g., saline, pharmaceuticals, or the like) into the blood circuit 120 from an infusion fluid container 702. In another example, the pump 700 helps drive the infusion fluid into the circulatory system of a patient. For instance, the pump 700 may communicate with the fluid combiner 226. Accordingly, the pump 700 may drive infusion fluid

In another example, system 100 may drive the infusion fluid into the blood circuit 120 to replace one or more plasma constituents removed by the filters 200 (e.g., the filter 202, filter 212, or the like). The infusion fluid may facilitate removal of one or more plasma constituents (e.g. cytokines, or the like) from blood of a patient. For instance, the infusion fluid may help maintain hemodynamic stability of the patient during therapy with the system 100. In another example, the filtrate fluid provided by the filters 200 may include cytokines. The infusion fluid provided by the infusion pump 700 may not include cytokines. Accordingly, the system 100 may remove a first set of plasma constituents (e.g., cytokines, or the like) while maintaining a specified concentration of a second set of plasma constituents (e.g., water, electrolytes, or the like).

In yet another example, the infusion pump 700 may provide infusion fluid into the blood circuit 120 ahead of the one or more filters 200. For example, the infusion pump 700 may provide infusion fluid to an infusion fluid combiner 704. The infusion fluid combiner 704 may communication with the first filter 202. Accordingly, the infusion pump 700 may provide infusion fluid into the blood circuit 120 ahead of the filters 200. In an example, the infusion fluid may inhibit clotting of the filters 200. Thus, providing the infusion fluid ahead of the filters 200 may enhance performance of the blood filtration system 100 because clotting of the blood circuit 120 may be minimized, for example by the infusion pump 700 providing infusion fluid to the blood circuit 120.

Figure 8 illustrates a schematic view of still yet another example of portions of the blood filtration system 100, according to an embodiment of the present subject matter. The blood filtration system may include the controller 102. The controller 102 may include one or more of a pump module 800, a sensor module 802, or an assessment module 804. In an example, the pump module 800 may modulate the one or more pumps 232, for example to adjust one or more of pressure or flow rate through the pumps 232. In an example, the pump module 800 may modulate one or more of the blood pump 112, the filtrate pump 116, or the infusion pump 700.

The blood filtration system 100 may include the one or more sensors 126. For example, the system 100 may include (but is not limited to) one or more of a hematocrit sensor 806, a flow rate sensor 808, a pressure sensor 810, or a blood leak detector 812. The controller 102 may communicate with the sensors 126 to monitor one or more parameters of the system 100. For instance, the sensor module 802 may communicate with the sensors 126 to monitor the parameters of the system 100. For instance, the hematocrit sensor 806 may help determine a hematocrit value of blood flowing through the blood circuit 120 (shown in Figure 1). The flow rate sensor 808 may help determine a rate of flow of a fluid through the blood circuit 120. The pressure sensor 810 may help determine a pressure within the blood circuit 120 (e.g., a pressure applied to blood, filtrate fluid, or the like). In an example, the pressure sensor 810 (or a plurality of the pressure sensor 810) may help measure a pressure gradient across a filter membrane (e.g., a transmembrane pressure, transmural pressure, or the like). The blood leak detector 812 may help determine if cellular constituents are included in a filtrate fluid of the system 100. Accordingly, the controller 102 may cooperate with the sensors 126 to monitor one or more parameters of the blood filtration system 100.

The controller 102 may module the pumps 232 based on monitored parameters of the blood filtration system 100. For example, the pump module 800 may modulate one or more of the pumps 232 based on a measured hematocrit value of blood in the blood circuit 120.

The pump module 800 may modulate the pumps 232 based a measured flow rate. For instance, the pump module 800 may modulate the blood pump to achieve a specified flow rate of blood through the first filter. The pump module 800 may modulate the filtrate pump to achieve a specified flow rate of filtrate fluid. The pump module 800 may modulate the infusion pump 700 to achieve a specified flow rate of infusion fluid. Accordingly, the controller 102 may cooperate with the sensors and the pumps 232 to transmit fluid through the blood circuit 120.

In another example, the assessment module 804 may help the controller 102 operate the system 100. For instance, the assessment module 804 may compare data received from the sensors 126, and the pump module 800 may modulate the pumps 232 based on the compared data. For instance, the assessment module may compare a measured pressure (e.g., a pressure applied to blood by the blood pump 112, or the like) to a specified pressure threshold. The controller 102 may modulate the pumps 232 based on the comparison of the measured pressure to the specified pressure threshold. For instance, the pump module 800 may operate the pumps 232 to limit pressure applied to cellular constituents of blood in the blood circuit 120. In an example, the controller 102 may modulate the blood pump 112 to decrease pressure applied to blood when the pressure exceeds the specified pressure threshold.

Figure 9 illustrates a block diagram of an example machine 900 upon which any one or more of the techniques (e.g., methodologies,) discussed herein may perform. Examples, as described herein, may include, or may operate by, logic or a number of components, or mechanisms in the machine 900. Circuitry (e.g., processing circuitry) is a collection of circuits implemented in tangible entities of the machine 900 that include hardware (e.g., simple circuits, gates, logic, etc.). Circuitry membership may be flexible over time.

Circuitries include members that may, alone or in combination, perform specified operations when operating. In an example, hardware of the circuitry may be immutably designed to carry out a specific operation (e.g., hardwired). In an example, the hardware of the circuitry may include variably connected physical components (e.g., execution units, transistors, simple circuits, etc.) including a machine readable medium physically modified (e.g., magnetically, electrically, moveable placement of invariant massed particles, etc.) to encode instructions of the specific operation. In connecting the physical components, the underlying electrical properties of a hardware constituent are changed, for example, from an insulator to a conductor or vice versa. The instructions enable embedded hardware (e.g., the execution units or a loading mechanism) to create members of the circuitry in hardware via the variable connections to carry out portions of the specific operation when in operation. Accordingly, in an example, the machine readable medium elements are part of the circuitry or are communicatively coupled to the other components of the circuitry when the device is operating. In an example, any of the physical components may be used in more than one member of more than one circuitry. For example, under operation, execution units may be used in a first circuit of a first circuitry at one point in time and reused by a second circuit in the first circuitry, or by a third circuit in a second circuitry at a different time. Additional examples of these components with respect to the machine 900 follow.

In alternative embodiments, the machine 900 may operate as a standalone device or may be connected (e.g., networked) to other machines. In a networked deployment, the machine 900 may operate in the capacity of a server machine, a client machine, or both in server-client network environments. In an example, the machine 900 may act as a peer machine in peer-to-peer (P2P) (or other distributed) network environment. The machine 900 may be a personal computer (PC), a tablet PC, a set-top box (STB), a personal digital assistant (PDA), a mobile telephone, a web appliance, a network router, switch or bridge, or any machine capable of executing instructions (sequential or otherwise) that specify actions to be taken by that machine. Further, while only a single machine is illustrated, the term “machine” shall also be taken to include any collection of machines that individually or jointly execute a set (or multiple sets) of instructions to perform any one or more of the methodologies discussed herein, such as cloud computing, software as a service (SaaS), other computer cluster configurations.

The machine (e.g., computer system) 900 may include a hardware processor 902 (e.g., a central processing unit (CPU), a graphics processing unit (GPU), a hardware processor core, or any combination thereof), a main memory 904, a static memory (e.g., memory or storage for firmware, microcode, a basic-input-output (BIOS), unified extensible firmware interface (UEFI), etc.) 906, and mass storage 908 (e.g., hard drive, tape drive, flash storage, or other block devices) some or all of which may communicate with each other via an interlink (e.g., bus) 930. The machine 900 may further include a display unit 910, an alphanumeric input device 912 (e.g., a keyboard), and a user interface (UI) navigation device 914 (e.g., a mouse). In an example, the display unit 910, input device 912 and UI navigation device 914 may be a touch screen display. The machine 900 may additionally include a storage device (e.g., drive unit) 908, a signal generation device 918 (e.g., a speaker), a network interface device 920, and one or more sensors 916, such as a global positioning system (GPS) sensor, compass, accelerometer, or other sensor. The machine 900 may include an output controller 928, such as a serial (e.g., universal serial bus (USB), parallel, or other wired or wireless (e.g., infrared (IR), near field communication (NFC), etc.) connection to communicate or control one or more peripheral devices (e.g., a printer, card reader, etc.).

Registers of the processor 902, the main memory 904, the static memory 906, or the mass storage 908 may be, or include, a machine readable medium 922 on which is stored one or more sets of data structures or instructions 924 (e.g., software) embodying or utilized by any one or more of the techniques or functions described herein. The instructions 924 may also reside, completely or at least partially, within any of registers of the processor 902, the main memory 904, the static memory 906, or the mass storage 908 during execution thereof by the machine 900. In an example, one or any combination of the hardware processor 902, the main memory 904, the static memory 906, or the mass storage 908 may constitute the machine readable media 922. While the machine readable medium 922 is illustrated as a single medium, the term "machine readable medium" may include a single medium or multiple media (e.g., a centralized or distributed database, and/or associated caches and servers) configured to store the one or more instructions 924.

The term “machine readable medium” may include any medium that is capable of storing, encoding, or carrying instructions for execution by the machine 900 and that cause the machine 900 to perform any one or more of the techniques of the present disclosure, or that is capable of storing, encoding or carrying data structures used by or associated with such instructions. Non-limiting machine readable medium examples may include solid-state memories, optical media, magnetic media, and signals (e.g., radio frequency signals, other photon based signals, sound signals, etc.). In an example, a non-transitory machine readable medium comprises a machine readable medium with a plurality of particles having invariant (e.g., rest) mass, and thus are compositions of matter. Accordingly, non-transitory machine- readable media are machine readable media that do not include transitory propagating signals. Specific examples of non-transitory machine readable media may include: non volatile memory, such as semiconductor memory devices (e.g., Electrically Programmable Read-Only Memory (EPROM), Electrically Erasable Programmable Read-Only Memory (EEPROM)) and flash memory devices; magnetic disks, such as internal hard disks and removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

The instructions 924 may be further transmitted or received over a communications network 926 using a transmission medium via the network interface device 920 utilizing any one of a number of transfer protocols (e.g., frame relay, internet protocol (IP), transmission control protocol (TCP), user datagram protocol (UDP), hypertext transfer protocol (HTTP), etc.). Example communication networks may include a local area network (LAN), a wide area network (WAN), a packet data network (e.g., the Internet), mobile telephone networks (e.g., cellular networks), Plain Old Telephone (POTS) networks, and wireless data networks (e.g., Institute of Electrical and Electronics Engineers (IEEE) 802.11 family of standards known as Wi-Fi®, IEEE 802.16 family of standards known as WiMax®), IEEE 802.15.4 family of standards, peer-to-peer (P2P) networks, among others. In an example, the network interface device 920 may include one or more physical jacks (e.g., Ethernet, coaxial, or phone jacks) or one or more antennas to connect to the communications network 926. In an example, the network interface device 920 may include a plurality of antennas to wirelessly communicate using at least one of single-input multiple-output (SIMO), multiple-input multiple-output (MIMO), or multiple-input single-output (MISO) techniques. The term “transmission medium” shall be taken to include any intangible medium that is capable of storing, encoding or carrying instructions for execution by the machine 900, and includes digital or analog communications signals or other intangible medium to facilitate communication of such software. A transmission medium is a machine readable medium.

Figure 10 shows one example of a method 1000 for reducing an amount of plasma constituents in blood of a patient, including one or more of the blood filtration system 100 described herein. In describing the method 1000, reference is made to one or more components, features, functions and operations previously described herein. Where convenient, reference is made to the components, features, operations and the like with reference numerals. The reference numerals provided are exemplary and are not exclusive. For instance, components, features, functions, operations and the like described in the method 1000 include, but are not limited to, the corresponding numbered elements provided herein and other corresponding elements described herein (both numbered and unnumbered) as well as their equivalents.

At 1002, the method 1000 may include communicating with the one or more sensors 126 of the blood filtration system 100. For instance, the sensor module 902 may communicate with one or more of the hematocrit sensor 806, the flow rate sensor 808, the pressure sensor 810, or the blood leak detector 812. The method 1004 may include at 1004 modulating one or more pumps based on the communication with the one or more sensors 126. For instance, the pump module 800 may modulate the blood pump 112 to limit pressure applied to cellular constituents of blood in the blood circuit 120.

Various Notes & Aspects

Example 1 is a blood filtration system configured to reduce one or more plasma constituents in blood of a patient, the system comprising: a first filter including a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; a second filter including a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter; a variable- speed blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through the first filter, and into an infusion line; and the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a variable-speed filtration pump configured to extract the filtrate fluid from the first filter and pressurize flow of the filtrate fluid into the second filter at a second pressure; and wherein the second pressure is higher than the first pressure.

In Example 2, the subject matter of Example 1 optionally includes wherein the blood filtration system is configured to generate a pressure gradient across the second filter membrane that exceeds a hemolysis pressure.

In Example 3, the subject matter of Example 2 optionally includes wherein: the hemolysis pressure includes a range of pressures; the range of pressures includes a first bounding point and a second bounding point; the first bounding point is approximately -600 mmHg; and the second bounding point is approximately +1,000 mmHg.

In Example 4, the subject matter of Example 3 optionally includes wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

In Example 5, the subject matter of any one or more of Examples 1-4 optionally include wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

In Example 6, the subject matter of any one or more of Examples 1-5 optionally include wherein: the first filter provides a return fluid that includes cellular blood constituents; and the filtrate fluid provided by the first filter does not include the cellular blood constituents. In Example 7, the subject matter of any one or more of Examples 1-6 optionally include wherein the first filter membrane has a first pore size and the second filter membrane has a second pore size, and the second pore size is less than the first pore size.

In Example 8, the subject matter of Example 7 optionally includes daltons.

In Example 9, the subject matter of Example 8 optionally includes daltons.

In Example 10, the subject matter of any one or more of Examples 7-9 optionally include daltons.

In Example 11, the subject matter of any one or more of Examples 1-10 optionally include wherein the one or more plasma constituents include one or more cytokines, and the second filter membrane is configured to allow the cytokines to flow across the second filter membrane.

In Example 12, the subject matter of any one or more of Examples 1-11 optionally include wherein: the filtrate fluid provided by the first filter is a first filtrate fluid the second filter provides a second filtrate fluid that includes the second set of plasma constituents; and the blood filtration system includes a third filter configured to receive the second filtrate fluid and reduce a third set of plasma constituents in the second filtrate fluid.

In Example 13, the subject matter of Example 12 optionally includes wherein the third set of plasma constituents includes cytokines.

In Example 14, the subject matter of Example 13 optionally includes wherein the third filter provides a third filtrate fluid including one or more of water or electrolytes.

In Example 15, the subject matter of any one or more of Examples 12-14 optionally include wherein the third filter provides a third filtrate fluid including one or more of water or electrolytes.

In Example 16, the subject matter of any one or more of Examples 12-15 optionally include wherein the third filter is configured to provide a filtered second filtrate fluid to a discharge port of the third filter.

In Example 17, the subject matter of any one or more of Examples 12-16 optionally include wherein in the second filter membrane is configured to allow the third set of plasma constituents to flow across the second filter membrane and inhibit albumin flow across the second filter membrane. In Example 18, the subject matter of any one or more of Examples 1-17 optionally include wherein the filter includes an anti -coagulant coating coupled with one or more of the first filter or the second filter.

In Example 19, the subject matter of any one or more of Examples 1-18 optionally include wherein the blood filtration system is configured to provide a notification of cytokine clearance, wherein cytokine clearance is based on one or more of blood flow rate pumped by the blood pump, a sieving coefficient of one or more of the first filter or the second filter, a filtration rate, or an infusion rate of an infusion fluid.

In Example 20, the subject matter of any one or more of Examples 1-19 optionally include a blood circuit configured to couple with the blood filtration system and including a catheter, the withdrawal line, and the infusion line, wherein: the withdrawal line and the infusion line are configured to couple with the catheter; and the catheter is configured for insertion into a blood stream of the patient.

Example 21 is a blood filtration system comprising: a blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through a first filter, and into an infusion line; and the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a filtration pump, wherein: the filtration pump is configured to extract a filtrate fluid from the first filter and pressurize flow of the filtrate fluid into a second filter at a second pressure; and wherein the second pressure is higher than the first pressure.

In Example 22, the subject matter of Example 21 optionally includes the first filter, wherein the first filter includes a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; and the second filter, wherein the second filter includes a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter.

In Example 23, the subject matter of Example 22 optionally includes wherein the first filter and the second filter are included in a blood circuit, and the blood circuit is configured for selective coupling with one or more of the blood pump or the filtration pump.

In Example 24, the subject matter of any one or more of Examples 22-23 optionally include a catheter configured for insertion into a blood stream of the patient; the withdrawal line, wherein the withdrawal line is configured to couple with the catheter; and the infusion line, wherein the infusion line is configured to couple with the catheter. In Example 25, the subject matter of any one or more of Examples 21-24 optionally include wherein: one or more of the first filter, the second filter, the withdrawal line, or the infusion line are included in a blood circuit; and the blood pump is a peristaltic pump, and the peristaltic pump is configured to engage with a portion of the blood circuit to pump blood through one or more components of the blood circuit.

In Example 26, the subject matter of any one or more of Examples 21-25 optionally include wherein the blood filtration system is configured to generate a pressure gradient across the second filter membrane that exceeds a hemolysis pressure.

In Example 27, the subject matter of Example 26 optionally includes wherein the hemolysis pressure includes a hemolysis pressure of the one or more plasma constituents of blood flowing through the first filter.

In Example 28, the subject matter of any one or more of Examples 21-27 optionally include wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

Example 29 is a blood filtration system configured to reduce one or more plasma constituents in blood of a patient, the system comprising: a first filter including a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; a second filter including a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter; a variable- speed blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through the first filter, and into an infusion line; and the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a variable-speed filtration pump configured to extract the filtrate fluid from the first filter and pressurize flow of the filtrate fluid into the second filter at a second pressure; and wherein the second pressure is higher than the first pressure, and the second pressure generates a pressure gradient across the second filter membrane that exceeds a hemolysis pressure of at least one of the one or more plasma constituents of blood flowing through the first filter.

In Example 30, the subject matter of Example 29 optionally includes wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane. In Example 31, the subject matter of any one or more of Examples 29-30 optionally include wherein: the first filter provides a return fluid that includes cellular blood constituents; and the filtrate fluid provided by the first filter does not include the cellular blood constituents.

Example 32 is a controller for a blood filtration system, the controller including: a pump module configured to modulate one or more of a blood pump or a filtration pump, wherein: the blood pump is configured to pump blood in a blood circuit including a first filter, the first filter configured to remove a first set of plasma constituents from the blood; the filtration pump is configured to extract a filtrate fluid from the first filter, the filtrate fluid including the second set of plasma constituents; the pump module is configured to modulate the blood pump to pressurize flow of blood into the first filter at a first pressure; the pump module is configured to operate the filtration pump to pressurize flow of the filtrate fluid into a second filter at a second pressure; and the second pressure exceeds the first pressure.

In Example 33, the subject matter of Example 32 optionally includes a sensor module configured to communicate with one or more sensors of the blood filtration system, the one or more sensors including a first pressure sensor configured to monitor at least the first pressure; an assessment module, wherein: the assessment module is configured to compare the first pressure to a first pressure threshold; and the pump module is configured to modulate the blood pump when the first pressure exceeds the first pressure threshold.

In Example 34, the subject matter of Example 33 optionally includes wherein the second pressure exceeds the first pressure threshold.

In Example 35, the subject matter of any one or more of Examples 33-34 optionally include wherein: the first pressure threshold includes a range of pressures; the range of pressures includes a first bounding point and a second bounding point; the first bounding point is approximately -600 mmHg; and the second bounding point is approximately +1,000 mmHg.

In Example 36, the subject matter of any one or more of Examples 33-35 optionally include wherein: the pump module is configured to modulate the blood pump and the infusion pump to generate a pressure gradient across the first filter; the assessment module is configured to compare the pressure gradient to the first pressure threshold; and the pump module is configured to modulate one or more of the blood pump or the filtration pump when the pressure gradient exceeds the first pressure threshold. In Example 37, the subject matter of any one or more of Examples 33-36 optionally include wherein the first pressure threshold corresponds with a hemolysis pressure of one or more of the first set of plasma constituents of blood flowing through the first filter.

Each of these non-limiting aspects can stand on its own, or can be combined in various permutations or combinations with one or more of the other aspects.

The above description includes references to the accompanying drawings, which form a part of the detailed description. The drawings show, by way of illustration, specific embodiments in which the invention can be practiced. These embodiments are also referred to herein as “examples.” Such examples can include elements in addition to those shown or described. However, the present inventors also contemplate examples in which only those elements shown or described are provided. Moreover, the present inventors also contemplate examples using any combination or permutation of those elements shown or described (or one or more aspects thereof), either with respect to a particular example (or one or more aspects thereof), or with respect to other examples (or one or more aspects thereof) shown or described herein.

In the event of inconsistent usages between this document and any documents so incorporated by reference, the usage in this document controls.

In this document, the terms “a” or “an” are used, as is common in patent documents, to include one or more than one, independent of any other instances or usages of “at least one” or “one or more.” In this document, the term “or” is used to refer to a nonexclusive or, such that “A or B” includes “A but not B,” “B but not A,” and “A and B,” unless otherwise indicated. In this document, the terms “including” and “in which” are used as the plain- English equivalents of the respective terms “comprising” and “wherein.” Also, in the following claims, the terms “including” and “comprising” are open-ended, that is, a system, device, article, composition, formulation, or process that includes elements in addition to those listed after such a term in a claim are still deemed to fall within the scope of that claim. Moreover, in the following claims, the terms “first,” “second,” and “third,” etc. are used merely as labels, and are not intended to impose numerical requirements on their objects.

Geometric terms, such as “parallel”, “perpendicular”, “round”, or “square”, are not intended to require absolute mathematical precision, unless the context indicates otherwise. Instead, such geometric terms allow for variations due to manufacturing or equivalent functions. For example, if an element is described as “round” or “generally round,” a component that is not precisely circular (e.g., one that is slightly oblong or is a many-sided polygon) is still encompassed by this description.

Method examples described herein can be machine or computer-implemented at least in part. Some examples can include a computer-readable medium or machine-readable medium encoded with instructions operable to configure an electronic device to perform methods as described in the above examples. An implementation of such methods can include code, such as microcode, assembly language code, a higher-level language code, or the like. Such code can include computer readable instructions for performing various methods. The code may form portions of computer program products. Further, in an example, the code can be tangibly stored on one or more volatile, non-transitory, or non volatile tangible computer-readable media, such as during execution or at other times. Examples of these tangible computer-readable media can include, but are not limited to, hard disks, removable magnetic disks, removable optical disks (e.g., compact disks and digital video disks), magnetic cassettes, memory cards or sticks, random access memories (RAMs), read only memories (ROMs), and the like.

The above description is intended to be illustrative, and not restrictive. For example, the above-described examples (or one or more aspects thereof) may be used in combination with each other. Other embodiments can be used, such as by one of ordinary skill in the art upon reviewing the above description. The Abstract is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. Also, in the above Detailed Description, various features may be grouped together to streamline the disclosure. This should not be interpreted as intending that an unclaimed disclosed feature is essential to any claim. Rather, inventive subject matter may lie in less than all features of a particular disclosed embodiment. Thus, the following claims are hereby incorporated into the Detailed Description as examples or embodiments, with each claim standing on its own as a separate embodiment, and it is contemplated that such embodiments can be combined with each other in various combinations or permutations. The scope of the invention should be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled.

Claims

THE CLAIMED INVENTION IS:

1. A blood filtration system configured to reduce one or more plasma constituents in blood of a patient, the system comprising: a first filter including a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; a second filter including a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter; and a variable-speed blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through the first filter, and into an infusion line; and the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a variable-speed filtration pump configured to extract the filtrate fluid from the first filter and pressurize flow of the filtrate fluid into the second filter at a second pressure; and wherein the second pressure is higher than the first pressure.

2. The blood filtration system of claim 1, wherein the blood filtration system is configured to generate a pressure gradient across the second filter membrane that exceeds a hemolysis pressure.

3. The blood filtration system of claim 2, wherein: the hemolysis pressure includes a range of pressures; the range of pressures includes a first bounding point and a second bounding point; the first bounding point is approximately -600 mmHg; and the second bounding point is approximately +1,000 mmHg.

4. The blood filtration system of claim 3, wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

5. The blood filtration system of claim 1, wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

6. The blood filtration system of claim 1, wherein: the first filter provides a return fluid that includes cellular blood constituents; and the filtrate fluid provided by the first filter does not include the cellular blood constituents.

7. The blood filtration system of claim 1, wherein the first filter membrane has a first pore size and the second filter membrane has a second pore size, and the second pore size is less than the first pore size.

8. The blood filtration system of claim 7, wherein the first filter membrane is configured to inhibit flow across the first filter membrane of molecules within a range of approximately 85,000 daltons to approximately 115,000 daltons.

9. The blood filtration system of claim 8, wherein the second filter membrane is configured to inhibit flow across the second filter membrane of molecules within a range of approximately 50,000 daltons to approximately 80,000 daltons.

10. The blood filtration system of claim 7, wherein the second filter membrane is configured to inhibit flow across the second filter membrane of molecules within a range of approximately 50,000 daltons to approximately 80,000 daltons.

11. The blood filtration system of claim 1, wherein the one or more plasma constituents include one or more cytokines, and the second filter membrane is configured to allow the cytokines to flow across the second filter membrane.

12. The blood filtration system of claim 1, wherein: the filtrate fluid provided by the first filter is a first filtrate fluid; the second filter provides a second filtrate fluid that includes the second set of plasma constituents; and the blood filtration system includes a third filter configured to receive the second filtrate fluid and reduce a third set of plasma constituents in the second filtrate fluid.

13. The blood filtration system of claim 12, wherein the third set of plasma constituents includes cytokines.

14. The blood filtration system of claim 13, wherein the third filter provides a third filtrate fluid including one or more of water or electrolytes.

15. The blood filtration system of claim 12, wherein the third filter provides a third filtrate fluid including one or more of water or electrolytes.

16. The blood filtration system of claim 12, wherein the third filter is configured to provide a filtered second filtrate fluid to a discharge port of the third filter.

17. The blood filtration system of claim 12, wherein in the second filter membrane is configured to allow the third set of plasma constituents to flow across the second filter membrane and inhibit albumin flow across the second filter membrane.

18. The blood filtration system of claim 1, wherein the filter includes an anti -coagulant coating coupled with one or more of the first filter or the second filter.

19. The blood filtration system of claim 1, wherein the blood filtration system is configured to provide a notification of cytokine clearance, wherein cytokine clearance is based on one or more of blood flow rate pumped by the blood pump, a sieving coefficient of one or more of the first filter or the second filter, a filtration rate, or an infusion rate of an infusion fluid.

20. The blood filtration system of claim 1, further comprising: a blood circuit configured to couple with the blood filtration system and including a catheter, the withdrawal line, and the infusion line, wherein: the withdrawal line and the infusion line are configured to couple with the catheter; and the catheter is configured for insertion into a blood stream of the patient.

21 A blood filtration system comprising: a blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through a first filter, and into an infusion line; the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a filtration pump, wherein: the filtration pump is configured to extract a filtrate fluid from the first filter and pressurize flow of the filtrate fluid into a second filter at a second pressure; and wherein the second pressure is higher than the first pressure.

22. The blood filtration system of claim 21, further comprising: the first filter, wherein the first filter includes a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; and the second filter, wherein the second filter includes a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter.

23. The blood filtration system of claim 22, wherein the first filter and the second filter are included in a blood circuit, and the blood circuit is configured for selective coupling with one or more of the blood pump or the filtration pump.

24. The blood filtration system of claim 22, further comprising: a catheter configured for insertion into a blood stream of the patient; the withdrawal line, wherein the withdrawal line is configured to couple with the catheter; and the infusion line, wherein the infusion line is configured to couple with the catheter.

25. The blood filtration system of claim 21, wherein: one or more of the first filter, the second filter, the withdrawal line, or the infusion line are included in a blood circuit; and the blood pump is a peristaltic pump, and the peristaltic pump is configured to engage with a portion of the blood circuit to pump blood through one or more components of the blood circuit.

26. The blood filtration system of claim 21, wherein the blood filtration system is configured to generate a pressure gradient across the second filter membrane that exceeds a hemolysis pressure.

27. The blood filtration system of claim 26, wherein the hemolysis pressure includes a hemolysis pressure of the one or more plasma constituents of blood flowing through the first filter.

28. The blood filtration system of claim 21, wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

29. A blood filtration system configured to reduce one or more plasma constituents in blood of a patient, the system comprising: a first filter including a first filter membrane configured to reduce an amount of a first set of plasma constituents in blood flowing through the first filter and provide a filtrate fluid including the first set of filtered plasma constituents; a second filter including a second filter membrane configured to reduce an amount of a second set of plasma constituents in the filtrate fluid provided by the first filter; and a variable-speed blood pump, wherein: the blood pump is configured to pump blood in a withdrawal line, through the first filter, and into an infusion line; and the blood pump is configured to pressurize flow of blood into the first filter at a first pressure; and a variable-speed filtration pump configured to extract the filtrate fluid from the first filter and pressurize flow of the filtrate fluid into the second filter at a second pressure; and wherein the second pressure is higher than the first pressure, and the second pressure generates a pressure gradient across the second filter membrane that exceeds a hemolysis pressure of at least one of the one or more plasma constituents of blood flowing through the first filter.

30. The blood filtration system of claim 29, wherein in the first filter membrane is configured to allow albumin to flow across the first filter membrane and inhibit red blood cell flow across the first filter membrane.

31. The blood filtration system of claim 29, wherein: the first filter provides a return fluid that includes cellular blood constituents; and the filtrate fluid provided by the first filter does not include the cellular blood constituents.

32. A controller for a blood filtration system, the controller including: a pump module configured to modulate one or more of a blood pump or a filtration pump, wherein: the blood pump is configured to pump blood in a blood circuit including a first filter, the first filter configured to remove a first set of plasma constituents from the blood; the filtration pump is configured to extract a filtrate fluid from the first filter, the filtrate fluid including the second set of plasma constituents; the pump module is configured to modulate the blood pump to pressurize flow of blood into the first filter at a first pressure; the pump module is configured to operate the filtration pump to pressurize flow of the filtrate fluid into a second filter at a second pressure; and the second pressure exceeds the first pressure.

33. The controller of claim 32, further comprising: a sensor module configured to communicate with one or more sensors of the blood filtration system, the one or more sensors including a first pressure sensor configured to monitor at least the first pressure; and an assessment module, wherein: the assessment module is configured to compare the first pressure to a first pressure threshold; and the pump module is configured to modulate the blood pump when the first pressure exceeds the first pressure threshold.

34. The controller of claim 33, wherein the second pressure exceeds the first pressure threshold.

35. The controller of claim 33, wherein: the first pressure threshold includes a range of pressures; the range of pressures includes a first bounding point and a second bounding point; the first bounding point is approximately -600 mmHg; and the second bounding point is approximately +1,000 mmHg.

36. The controller of claim 33, wherein: the pump module is configured to modulate the blood pump and the infusion pump to generate a pressure gradient across the first filter; the assessment module is configured to compare the pressure gradient to the first pressure threshold; and the pump module is configured to modulate one or more of the blood pump or the filtration pump when the pressure gradient exceeds the first pressure threshold.

37. The controller of claim 33, wherein the first pressure threshold corresponds with a hemolysis pressure of one or more of the first set of plasma constituents of blood flowing through the first filter.