JP4762503B2 - Apheresis equipment - Google Patents

Description

  The present invention relates to an apheresis device. More specifically, the present invention relates to increasing the production efficiency of blood products by appropriately arranging sterile air in a sterile circuit in an apheresis device of the type that produces blood products using a leukocyte removal filter.

  As one of the mainstream methods of apheresis, there is a method adopted in the apparatus of the present applicant, Hemonetics. This involves collecting whole blood from blood donors and / or blood donors, and into the high density components (red blood cells), medium density components (mainly platelets and white blood cells), and low density components (plasma) in the centrifuge. A so-called “draw” step that separates the blood components concentrically with each other, and a so-called “return” step in which the blood components remaining in the centrifuge are returned to the donor and / or donor after separating the necessary blood components. It is made into a component. Until now, apheresis has been improved by various methods. Among them, as described in Patent Document 1, low-density components collected outside the centrifuge are recirculated to the centrifuge for a short period of time. As described in the so-called “dwell” technology and Patent Document 2, etc., low density components are recirculated into the centrifuge at a surge flow rate, that is, a flow rate that increases with time, and platelets and the like are removed from the intermediate density components. There are so-called “surge” technologies that preferentially flow out. Typically, apheresis collects a predetermined blood component by repeating one cycle composed of a combination of processes such as draw, dwell, surge, and return several times.

As a typical centrifuge used in apheresis, a Latham bowl is well known. This is described in, for example, Patent Document 3, and has an inlet port and an outlet port, and has a separation space for separating collected whole blood into components. The centrifuge bowl is usually configured as a closed circuit together with a venous needle, a blood bag, and a flexible tube connecting them, and is used as a disposable kit called a disposable. An example of such a disposable is shown in FIG. 1B of Patent Document 1 and FIG. 2 of Patent Document 4. Disposables are variously configured according to various protocols for blood treatment, such as PLP (platelet and plasma collection) protocol, PPP (platelet poor plasma collection) protocol, etc., but in any case manufactured in a sterile environment Then, it is stored in a sealed container and supplied to the blood collection site. In use, the operator selects the disposable according to the protocol, removes the disposable from the sealed container, and attaches it to the apheresis device in accordance with the prescribed conditions. After collecting blood components according to the protocol, the operator removes the disposable and obtains the required formulation in a blood bag. The remaining part is disposed of in accordance with the law.
Patent No. 2776988 U.S. Pat. No. 4,416,654 US Pat. No. 3,145,713 Japanese Patent No. 3196838

As a disposable used so far for producing a leukocyte-removing preparation, one using a leukocyte filter is known. As a device used in the apparatus of the present applicant, Hemonetics, for example, there is a disposable used in an LDPLP (leukocyte-removed platelet and plasma collection) protocol. This has a blood component temporary storage bag for storing platelets flowing out of the centrifuge bowl, and a platelet bag after removal of leukocytes connected to the temporary storage bag via a tube, and a leukocyte filter is arranged in the middle of this tube Has been. In use, the tube is attached to a valve between the blood component temporary storage bag and the leukocyte removal filter. After a predetermined number of cycles of platelets are collected in a temporary storage bag with the valve closed, the valve is opened, the platelets are filtered by a leukocyte removal filter with a drop, and the white blood cells are removed at a time. This method is called a batch method.
However, if the tube between the blood component temporary storage bag and the leukocyte removal filter is not properly attached to the valve due to operator error, etc., it will be collected in the blood component temporary storage bag immediately after the first cycle of platelet collection. Platelets flow out to the platelet bag after the leukocyte removal through the leukocyte filter. When collecting platelets in the second cycle, all the platelets collected in the first cycle have passed through the filter, so the inflow side of the leukocyte removal filter is filled with air, and the inflowing platelets are not allowed to pass through (air Block) may occur. This is considered to be caused by the presence of a sufficient amount of sterile air in advance in the blood component temporary storage bag to fill the inflow side of the leukocyte removal filter.
Even when the tube is correctly attached to the valve, platelets remain on the outflow side of the leukocyte removal filter after all the platelets have passed through the leukocyte removal filter. Here, if the platelets remaining on the leukocyte removal filter can be pushed out with plasma, the platelets can be collected without waste. However, in the batch method, the removal of leukocytes is started after collecting a predetermined amount of all platelets in a blood component temporary storage bag, so the centrifugal rotation is maintained until all the platelets pass through the leukocyte removal filter, and then the plasma is removed from the blood. Delivery to a temporary ingredient storage bag greatly extends the processing time. In addition, if the plasma used to push out platelets from the leukocyte removal filter is sent to the blood component temporary storage bag while the platelets are present in the blood component temporary storage bag, the platelet and plasma are mixed in the blood component temporary storage bag. It is not appropriate. Further, it is difficult to continuously pass blood plasma after platelets through a leukocyte removal filter without generating an air block unless other liquid sensors are provided.
Furthermore, even if leukocytes are successfully removed, it is considered that platelets coexist in the platelet bag after removal of leukocytes together with sterile air causes platelet primary aggregation. Therefore, at the blood donation and / or blood donation site, after removing the venous needle from the blood donor and / or blood donor, the sterile air present in the platelet bag after the leukocyte removal after the leukocyte removal is pushed by the bag manually. It is moved to the other part of the aseptic circuit by a simple operation (air removal action). An object of the present invention is to solve the problems as described above.

According to the present invention, in a preparatory stage before a disposable needle is attached to an apheresis device and a venous needle is punctured to a blood donor and / or a blood donor, the sterile component in a blood component temporary storage bag, which is usually a flexible container, is used. Air is moved to other parts of the disposable. This keeps the blood component temporary storage bag free of sterile air, and prevents air blocks from being generated even when leukocyte removal is started immediately after the collection of platelets in the first cycle. In other words, the valve for opening and closing the tube, that is, the tube between the leukocyte removal filter and the blood component temporary storage bag, which is required in the conventional batch method, becomes unnecessary, and leukocyte removal by the leukocyte removal filter is continuously performed. It becomes possible. Preferably, aseptic air is discharged from a predetermined blood component preparation bag connected downstream of the blood component temporary storage bag via a leukocyte removal filter, for example, a platelet bag after leukocyte removal or a plasma bag after leukocyte removal, and is also disposable. Moved to another part.
Aseptic air can be discharged from the blood component temporary storage bag and, if necessary, the platelet bag after removing leukocytes or the plasma bag after removing leukocytes using a pump provided in the apheresis device. This is a type called a peristaltic pump, and one or two are used for the purpose of feeding whole blood to a centrifuge or circulating the collected plasma through the centrifuge. In addition, a normal apheresis device is provided with a pump for mixing an anticoagulant with whole blood. The pump, for example, moves sterile air from a blood component temporary storage bag through a tube connecting each to a plasma bag via a centrifuge. The pump is usually under the control of a control means such as a microcomputer, and this control means controls the rotation of each part of the apheresis device, for example, a centrifuge bowl attached, and the opening / closing of a valve, according to various protocols.
In any cycle, after the platelets flow out from the blood component temporary storage bag to the platelet bag after the leukocyte removal, the blood component temporary storage bag can maintain a state in which aseptic air still does not exist, so leukocyte removal is continuously performed. It becomes possible. In addition, after platelet collection in the final cycle, the blood component temporary storage bag has only platelets for the final cycle. Therefore, in the final cycle, leukocyte removal is completed in a short time after platelet collection compared to the batch method. Therefore, after platelets collected in the final cycle are discharged from the blood component temporary storage bag, blood donation is performed without mixing the platelets and plasma collected in the blood component temporary storage bag or generating an air block as in the batch method. Plasma from a person and / or donor can be collected in a blood component temporary storage bag, or plasma already collected in a plasma bag can be transferred to a blood component temporary storage bag. Thereby, after the platelets have passed through the leukocyte removal filter, it is possible to pass the plasma through the leukocyte removal filter, and the platelets remaining in the leukocyte removal filter can be pushed out to the platelet bag after the leukocyte removal. Furthermore, any amount of plasma collected in the plasma bag can be transferred to the blood component temporary storage bag, and the plasma can be filtered with a leukocyte removal filter.
In addition, according to the present invention, since the leukocyte removal of platelets is completed at an early stage, the line leading from the centrifuge bowl to the blood component temporary storage bag can be opened without returning the collected platelets when returning blood in the final cycle. It becomes possible, and after the leukocyte removal, aseptic air in the platelet bag after the leukocyte removal can be sucked out by the pump, for example, to the leukocyte removal filter. As a result, after removing leukocytes, aseptic air present together with platelets in the platelet bag after leukocyte removal can be reduced to prevent primary platelet aggregation, and it is also possible to reduce the work load due to the air removal action that has been conventionally performed.

  As described above, according to the present invention, sterilized air that causes an air block in the leukocyte removal filter is removed at the appropriate place in the sterilization circuit, that is, the disposable, at the latest before the start of the first platelet collection, preferably before the start of blood collection. By moving to, it is possible to prevent air block and to remove leukocytes with a leukocyte removal filter at any time, preferably continuously. Immediately after removing the leukocytes from the platelets, plasma can be passed through the leukocyte removal filter without mixing with the platelets. it can. Furthermore, leukocyte removal can be performed on the collected plasma using a leukocyte removal filter, and the quality of the preparation can be improved by removing aseptic air from the platelet bag after leukocyte removal.

  Referring to FIG. 1, the apheresis device E1 uses a standard Latham style centrifuge bowl CB1 to separate the anticoagulated whole blood into its components. However, of course, the centrifuge may be in other forms, for example, a centrifuge bowl integrally formed by a blow mold. The centrifuge bowl CB1 includes a rotatable bowl body, and a fixed inlet port PT1 and outlet port PT2 that are in fluid communication with the interior of the bowl by a rotary seal. A bag or container B1 for storing an anticoagulant (ACD) communicates with a tube T1 with a venous needle through a sterilization filter F2, a pump P3, a tube T2 passing through an air detector D3, and a connector C1. The tube T1 with a venous needle is connected to the air detector D1, the air detector D2, the blood filter chamber F1, the valve V1, the air detector D4, the tube T3 passing through the pump P1, the connector C2, the tube T4, and the inlet port PT1. And in fluid communication with the centrifuge bowl CB1. The outlet port PT2 of the centrifuge bowl CB1 is labeled as plasma suspended in the weigh scale S1 via a tube T5 passing through the line sensor L1, a three-way connector C3, a tube T12, a connector C4, and a tube T8 passing through the valve V2. Is selectively communicated with the container inlet port PT4 of the container B2. The container B4 labeled as air branches from the tube T5 via the connector C3, passes through the valve V4, passes through the tube T6, and further the container B3 labeled as temporary storage of blood components has its inlet port PT5. Are selectively communicated with the outlet port PT2 of the centrifuge bowl CB1 via a tube T9 that branches from the tube T5 via the connector C3, the tube T12, and the connector C4 and passes through the valve V3. The container outlet port PT3 of the container B2 extends through the pump P2 via the tube T7 and is connected to the connector C2. The container B5 labeled as platelet after leukocyte removal is connected to the outlet port PT6 of the container B3 via the tube T10, the leukocyte removal filter F3, the tube T11, the connector C5, and the tube T13. The container B6 labeled as plasma after leukocyte removal is connected to the outlet port PT6 of the container B3 via the tube T10, the leukocyte removal filter F3, the tube T11, the connector C5, and the tube T14. Here, the circuit is shown with the disposable attached to the apheresis device body, but the configuration of the disposable part is shown in FIG. In addition, the configuration of the apheresis device main body falls within the range of common sense for those skilled in the art when described in the above-mentioned Patent Document 1.

Pumps P1, P2 and P3, coupled with valves V1 to V6, are line sensor L1, blood donor and / or donor pressure monitor (DPM) M1, system pressure monitor (SPM) M2, and air detector D1, In accordance with signals generated by D2, D3, and D4, the direction and duration of the flow through the apheresis device E1 are controlled according to instructions from a microcomputer (not shown). Air detectors D1, D2, D3 and D4 detect the presence or absence of liquid. The pressure monitors M1 and M2 monitor the pressure level in the device E1. The line sensor L1 optically detects the presence of blood components passing through the line sensor L1 from the outlet port PT2. In some cases, the pumps P1 and P2 can be replaced by a single pump disposed along the tube T4 between the connector C2 and the inlet port PT1 of the centrifuge bowl CB1. However, in this case, the critical flow technique described later cannot be used, and the operation of returning the blood while diluting the concentrated erythrocyte with plasma at the time of returning the blood cannot be performed.
In the circuit mounting stage before the venous needle is punctured to the blood donor and / or blood donor, the pump P2 is energized, and the sterilized air in the containers B3, B5, and B6 is passed through the centrifuge bowl to the tubes T9 and T12. , Tube T5, tube T4, and tube T7 are transferred to container B2. At that time, the valves V3, V5 and V6 are opened, and the other valves are closed.
When the system pressure monitor M2 detects a predetermined negative pressure, the pump P2 is stopped and the valve V3 is closed. After a while, only the valve V2 is opened, and the non-uniform air pressure in the centrifuge bowl CB1 (negative pressure) and the container B2 (positive pressure) is made uniform. Thereafter, aseptic air does not flow into the container B3 and the downstream container until plasma or platelets are collected in the container B3.

  After the container B1 is connected, the pumps P1 and P3 are energized and the tube T2 of the apheresis device E1 is primed with an anticoagulant from the container B1. At this time, T1 is clamped. The anticoagulant passes through the sterilization filter F2 and the connector C1, and reaches the air detector D2. The air detector D2 detects the presence of the anticoagulant in D2 and terminates the anticoagulant priming operation. During the priming operation, the valves V1 and V4 are opened, and the sterilized air flowing out of the centrifuge bowl CB1 by the anticoagulant priming operation enters the container B4.

  Next, the tube T1 with a venous needle is inserted into the blood donor and / or blood donor, and the draw step is started. During the draw step, the whole blood collected from the blood donor and / or blood donor via the venous needle tube T1 is mixed in the connector C1 with the anticoagulant supplied from the container B1 by the pump P3. Further, the whole blood mixed with the anticoagulant by the pump P1 is supplied from the inlet port PT1 to the centrifuge bowl CB1 via the tube T3 and the tube T4. The operation of each pump, valve, etc. in the apheresis device E1 is performed according to the control of the microcomputer (not shown).

  When the centrifuge bowl CB1 rotates, the anticoagulated whole blood introduced to the bottom of the bowl is separated into different components such as high concentration, medium concentration and low concentration by centrifugal force according to the density of the components. The The number of rotations of the bowl can be selected from a range of, for example, 4000 to 6000 rpm, and is typically 4800 rpm, for example. Within the centrifuge bowl CB1, blood components form concentric layers from the outside to the inside, in order of increasing density. That is, the red blood cell layer is pushed to the outermost side, and the plasma layer is present near the center. A buffy coat layer composed of an inner layer of platelets, a transition layer of platelets and leukocytes, and an outer layer of leukocytes is formed between them. The plasma layer is the closest component to the outlet port PT2, and is first effluxed through the outlet port PT2 as anticoagulated whole blood is added to the centrifuge bowl CB1 through the inlet port PT1.

  Plasma that flows out from the outlet port PT2 during the draw step is collected in the container B2 via the tube T5, the connector C3, the tube T12, the connector C4, the valve V2, the tube T8, and the container inlet port PT4 that pass through the line sensor L1. Here, according to the critical flow technique, the plasma collected in the container B2 is pumped from the outlet port PT3 of the container B2 through the tube T7, the connector C2, and the tube T4 to the centrifuge bowl CB1 through the inlet port PT1. Circulated. In critical flow technology, the total plasma flow through the centrifuge during the draw step, ie the plasma flow in the whole blood drawn in the draw step, and from the vessel B2 to the centrifuge bowl CB1 for whole blood dilution. The total plasma flow that is circulated is referred to as the “critical flow” and is kept constant. Depending on the donor's and / or donor's venous pressure, etc., the whole blood supply rate will fluctuate during the draw step and may be zero in some cases. Plasma can be circulated to compensate for the drop, stabilizing the flow through the centrifuge bowl and preventing disruption of the separation. The circulating plasma also dilutes anticoagulated whole blood, facilitating separation of blood components in the centrifuge bowl.

  An optical sensor (not shown) is applied to the shoulder of the centrifuge bowl CB1 to monitor a layer in which blood components are concentrically formed in the centrifuge bowl. That is, the optical sensor monitors the radius from the rotation axis of the region occupied by the buffy coat in the centrifuge bowl CB1, and detects that this radius has reached a specific value. When the optical sensor detects the red blood cell layer in place, the draw step is complete, valve V1 is closed, pump P1 is stopped, and no further blood is taken from the donor and / or donor, The dwell phase begins.

  During the dwell, the pump P2 circulates plasma through the centrifuge bowl CB1 at a suitable flow rate, for example, 100 mL / min for a certain period. At this flow rate, the buffy coat is diluted and widened, but the platelets do not exit the centrifuge bowl CB1. As described in U.S. Patent No. 6,057,049, the dwell technique dilutes the buffy coat to achieve better separation of platelets and leukocytes and to allow stabilization of the flow pattern in the centrifuge bowl CB1. Thereafter, a surge step is started and platelets are collected. However, the dwell technology can be replaced with a high-speed critical flow in accordance with the proposal of Japanese Patent Application No. 2002-274519, and in this case, the process directly shifts from draw to surge.

In a surge, the speed of pump P2 is increased, for example, in increments of 5-10 mL / min, and plasma is circulated until a platelet surge rate of about 200-250 mL / min is reached. This platelet surge rate is a rate at which platelets can exit the centrifuge bowl CB1, but red blood cells or white blood cells cannot. The platelets flowing out with the plasma leaving the bowl become cloudy and cloudy, and this cloudiness is detected by the line sensor L1. The line sensor L1 can include an LED that irradiates light to a blood component that passes through the tube T5, and a photoelectric detector that receives light after passing through the blood component. The amount of light received by the photoelectric detector is correlated with the density of the liquid flowing through the tube T5. When platelets first start out of the centrifuge bowl CB1, the output of the line sensor L1 begins to decrease. Valve V3 is opened, valve V2 is closed, and platelets are collected in container B3. If most of the platelets are removed from the centrifuge bowl CB1, clouding of the outflowing liquid is reduced. This decrease in fog is detected by the line sensor L1. Thereafter, the valve V3 is closed and the platelet collection is completed.
According to the present invention, the platelets collected in the container B3 immediately pass through the leukocyte removal filter F3, and the platelets from which the leukocytes have been removed are collected in the container B5. This leukocyte removal is performed using a drop between the containers B3 and B5 arranged at different positions in the vertical direction. Since the container B3 is free of aseptic air, the platelets stop flowing out near the outlet port PT6 of the container B3. Therefore, no air block is generated in the leukocyte removal filter F3.
Additional blood can be collected after the surge is over. Similar to the draw step, additional blood collection is performed by supplying anticoagulated whole blood from the inlet port PT1 to the centrifuge bowl CB1 through the tube T3 and the tube T4 by the pump P1. Also in this case, critical flow technology can be used. The plasma flowing out from the outlet port PT2 of the centrifuge bowl CB1 during the additional blood collection is collected in the container B2 or collected in the container B3 in order to obtain the required amount of plasma. The plasma collected in the container B3 can be used to push the platelets remaining in the leukocyte removal filter F3 to the container B5.
Regardless of whether or not additional blood was collected, the surge was terminated and the platelets in the container B3 passed through the leukocyte removal filter F3, and then the plasma collected in the container B2 by the pump P2 was transferred to the tubes T7 and T4, the centrifuge bowl CB1, and the tube. It can be transferred to container B3 via T5, T12 and T9. At that time, the centrifugal rotation remains maintained. The plasma transferred to the container B3 can be used to push the platelets remaining in the leukocyte removal filter F3 to the container B5 through the tube T13 when additional blood collection is not performed, After the platelets are pushed out from the leukocyte removal filter F3 by plasma, the valves V5 and V6 are switched to obtain a plasma preparation which is collected in the container B6 via the tube T14 and from which leukocytes have been removed.
Thereafter, the centrifugal rotation stops, and the pump P1 is rotated in the return direction, whereby a return step for returning the concentrated red blood cells remaining in the centrifugal bowl CB1 is started. By the end of the return step, the removal of white blood cells from platelets and / or plasma is completed, and the container B3 is empty. The inlet port PT7 of the container B5 and the inlet port PT8 of the container B6 are located in the upper part of the container, and in the final cycle, these inlet ports PT7 and PT8 are located near the leukocyte removal filter F3 and the tube T10 at the start of blood processing. , There is sterile air remaining in T11, T13 and T14. When the valves V3 and V5 are opened in the return step of the final cycle after removing the leukocytes from the platelets and / or plasma, the sterilized air in the container B5 is passed through the tubes T13 and T11 by the pump P1, and the leukocytes It is transferred to the removal filter F3. After the system pressure monitor M2 detects that aseptic air has flowed out of the container B5, the valve V3 and V5 are closed to complete the air removal action of the container B5. When the valves V3 and V6 are opened, the sterile air in the container B6 is transferred to the leukocyte removal filter F3 through the tubes T14 and T11 by the pump P1. After aseptic air has flowed out of the container B6, the valve V3 and V6 are closed to complete the air removal action of the container B6. Since platelets do not remain in the leukocyte removal filter F3, sterile air mixed in the platelet bag after leukocyte removal and / or the leukocyte removal plasma bag after leukocyte removal is put into the leukocyte removal filter without affecting the platelet collection efficiency. It is possible to extract.

  The apheresis device of the present invention is expected to be useful for the efficient production of blood products.

It is the schematic which shows typically the preferable Example of the apheresis apparatus of this invention. FIG. 2 is a schematic view of an example of a disposable used when performing a simultaneous plasma and platelet collection protocol in the apheresis device of FIG. 1.

Explanation of symbols

E1 apheresis device CB1 centrifuge bowl P1-P3 pump T1-T12 tube V1-V4 valve B1-B5 bag F1-F2 filter F3 leukocyte removal filter

Claims (12)

A centrifuge having an inlet port and an outlet port for separating whole blood into a low density component, a medium density component, and a high density component;
A first container selectively in communication with the outlet port via a first passage;
A second container connected to the first container via a second passage;
A leukocyte removal filter disposed in the second passage;
In an apheresis device, comprising: pump means acting on a third passage connected to the inlet port; and control means for controlling the pump means and the centrifuge.
The control means operates the pump means before collecting at least a blood component in the first container, and discharges gas from the first container through the first passage. Apheresis device. 2. The apheresis device according to claim 1, wherein the control means discharges gas from the second container and the first container through the second passage and the first passage. A third passage selectively connected to each of the first passage and the third passage through a fourth passage and a fifth passage and connected to collect the low density component from the outlet port; The apheresis device according to claim 1, further comprising a container, wherein the discharged gas flows into the third container through the centrifuge and through the third passage and the fifth passage. . A first pump operable to supply the donor's whole blood from the inlet port to the centrifuge via the third passage; and the low-density component in the third container. And a second pump operable to return from the inlet port to the centrifuge via the fifth passage and the third passage, wherein the draining is performed by the second pump. 3. Apheresis device. The control means sends the intermediate density component from the centrifuge to the first container and the second container during blood processing, and then the low density component is sent to the centrifuge or the third container. The apheresis device according to any one of claims 1 to 4, wherein the pump means and the centrifuge are operated so as to be sent to the first container. A fourth container connected to the second passage via a sixth passage downstream of the leukocyte removal filter, wherein the control means operates the pump means before the start of blood treatment, The apheresis device according to claim 1, wherein gas is discharged from a fourth container through the sixth passage, the second passage, and the first passage. The control means operates the pump means and the centrifuge to deliver the intermediate density component from the centrifuge to the first container and the second container, and the intermediate density component is the first density component. 7. After being sent to the second container, the control means operates the pump means to discharge the gas present in the second container through the second passage. 1 apheresis device. The apheresis device according to any one of claims 1 to 7, wherein the control means discharges the gas prior to collection of whole blood. The apheresis device according to claim 1, wherein the gas is sterile air. Disposable including a centrifuge for separating the collected whole blood into blood components, the disposable
A first container selectively in communication with the outlet port of the centrifuge via a first passage;
A second container connected to the first container via a second passage;
An apheresis device comprising a leukocyte removal filter disposed in the second passage,
A method for preventing the occurrence of air block in the leukocyte-removing filter, the blood components prior to sampling to the first container, the gas present in the first container other of the disposable A method characterized by moving to a part. 11. The method of claim 10, wherein the gas transfer is performed prior to collection of whole blood. The method according to claim 10 or 11, wherein the movement of the gas is also performed from the second container.

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