JP2023554695A - Systems and methods for plasma collection - Google Patents

Abstract

Plasma exchange systems and plasmapheresis systems that determine the volume of plasma product (i.e., anticoagulated plasma) such that the target volume of pure plasma in the plasma product is determined based on donor-specific characteristics A method is provided for operating. In particular, the target amount of pure plasma to be collected is based on the donor's weight, or weight and height. The target volume of pure plasma (TVP) to be collected may be a multiple of the donor's body weight. Alternatively, TVP may be a multiple of the donor's total blood volume TBV, where the donor's TBV is determined based on the donor's weight and height. A target volume of plasma product to be collected, TVPP, is set and separation of whole blood into plasma and second components continues until the volume of plasma product in the collection container is equal to TVPP. . [Selection diagram] Figure 4

Description

[Cross reference to related applications]
This application claims priority to U.S. No. 17/306,099, filed May 3, 2021, and U.S. No. 63/140,534, filed January 22, 2021, and filed in 2020. U.S. No. 17/078,824 filed on Oct. 23, U.S. No. 17/062,368 filed on Oct. 2, 2020, and U.S. No. 17/062,368 filed on Oct. 25, 2020. No. 041,701, filed on January 10, 2020, U.S. No. 16/739,441, filed on May 21, 2019, PCT/US2019/033318, filed on May 10, 2019 No. 62/846,400, filed Oct. 30, 2018, and U.S. No. 62/674,144 filed May 21, 2018. as related, each of which is incorporated herein by reference in its entirety.

TECHNICAL FIELD This application relates to systems and methods for performing plasmapheresis, and more particularly to plasmapheresis systems and methods in which the volume of pure plasma that can be collected from a particular donor is optimized.

Plasmapheresis is an apheresis procedure that takes whole blood from a donor, keeps the plasma separate from other cellular blood components (red blood cells, platelets, and white blood cells), and returns the cellular blood components to the donor. Separation of plasma from cellular components is usually performed in automated procedures by centrifugation or membrane filtration.

In automated plasmapheresis, whole blood is collected from a donor, mixed with anticoagulants in a specific ratio, and then separated into plasma, red blood cells, and other cellular components. Once the target volume of anticoagulated plasma (or "plasma product") has been collected, as measured by the scale attached to the plasma collection container, collection of whole blood from the donor is stopped and red blood cells and other cellular components are returned to the donor. Often, the plasma product is collected in multiple collection and reinfusion cycles until the target total volume of anticoagulated plasma is collected. The anticoagulated plasma can be used for subsequent transfusions or further manufacturing.

Plasma collected to serve as raw material for further manufacturing (“raw plasma”) is collected from multiple donors and combined or pooled together for this purpose. To improve the consistency of source plasma manufacturing procedures and minimize the potential for staff error, FDA has published guidelines for registered blood collection centers regarding the volume of plasma that can be collected as raw plasma during plasmapheresis. was issued. (FDA Memo: "Volume Restrictions - Automated Collection of Source Plasma (11/4/92)").

The FDA memo is a simplified plasma volume nomogram that limits the volume (or weight) of pure (or raw) plasma that can be collected from a given donor to ensure donor safety and comfort. is listed. More specifically, the FDA nomogram limits the volume (or weight) of plasma based on the donor's weight and limits the amount of anticoagulant and anticoagulant to reach the maximum collection volume of plasma plus anticoagulant for a particular donor. Establishing the volume of anticoagulant that can be added such that the ratio of anticoagulated blood is 1:16, or 1 part anticoagulated blood to 0.06 part anticoagulant. .

The simplified nomogram described in the FDA memo is the primary method for determining collection volumes of plasma products used in blood collection centers. Therefore, plasmapheresis machines used in such centers generally have anticoagulants added to whole blood at a ratio of 1:16 or 0.06, according to the maximum collection volume allowed by the FDA nomogram. , is programmed to collect a specific volume/weight of anticoagulated plasma (assuming a known density).

One simplification made in the FDA nomogram is to exclude consideration of donor hematocrit when determining the target collection volume of plasma product. However, the relative proportions of pure plasma and anticoagulant in the plasma product vary depending on the hematocrit of the donor's blood and the rate at which the anticoagulant binds to the donor's whole blood. As a result, a donor with a high hematocrit will reach the maximum collection volume listed in the FDA nomogram before reaching the maximum volume of pure plasma that can be safely collected from the donor. This means inefficiencies for plasma collection centers in that the volume of pure plasma collected is less than the maximum possible.

Additionally, the amount of pure plasma that can be safely collected from a donor may depend on factors that affect the donor's total blood volume, such as the donor's height, in addition to the donor's weight and hematocrit.

As source plasma from multiple donors is combined, it is important to maximize the volume of pure plasma that can be collected from each individual donor. This is because even small increases in the volume collected from each individual donor add up to a significant increase in the total volume of pooled plasma. If the plasmapheresis machine could better target the volume of pure plasma, more plasma proteins could be collected from each donor, increasing the overall efficiency of the plasma collection center. Accordingly, the present disclosure provides systems and methods for optimizing the volume of plasma collected consistent with donor safety and comfort.

In a first aspect of the present disclosure, a system for collecting plasma from a donor is provided, the system comprising a venipuncture needle for collecting whole blood from the donor, and the whole blood containing plasma products and red blood cells. a blood separator for separating into second blood components; a donor line coupled to a venipuncture needle for introducing whole blood from the donor into the blood separator; and a second blood separator for controlling flow through the donor line. one pump, an anticoagulant line coupled to an anticoagulant source for combining anticoagulant with whole blood, and a second pump for controlling flow through the anticoagulant line. .

A touch screen is provided for receiving input from an operator to a control programmed to control operation of the system. The controller determines a target volume of plasma product to be collected (TVPP) based on the donor's weight and the donor's hematocrit, or based on the donor's weight and height and the donor's hematocrit, and collects whole blood from the donor. performing a collection and return cycle for collection, adding an anticoagulant to the whole blood at a predetermined ratio (ACR), separating the anticoagulated whole blood into a plasma product and a second component; 2 components are returned to the donor, and when the measured volume of plasma product in the plasma collection container reaches the target volume of plasma product, the collection of whole blood from the donor is stopped and the second blood component is returned to the donor. The system is configured to control operation of the system to initiate final return of the components.

In a second aspect, the controller determines i) a target volume (TVP) of pure plasma to be collected based on the donor's weight; and ii) a target volume of plasma product to be collected based on the donor's weight. is programmed to calculate the percentage of anticoagulant in (%AC _TVPP ) based on a predetermined anticoagulant ratio ACR and donor hematocrit, where TVPP=TVP/(1-%AC _TVPP ) It is.

In a third aspect, the controller determines, based on the donor's weight and height, the total blood volume (TBV) of the donor, the target volume of pure plasma (TVP) to be collected as a percentage of TBV, and a predetermined It is programmed to calculate the percentage of anticoagulant in the target volume of plasma product collected (%AC _TVPP ) based on the coagulant ratio (ACR) and donor hematocrit, where TVPP=TVP/ (1-% AC _TVPP ).

In a fourth aspect, the controller calculates the donor's total blood volume (TBV) based on the donor's weight and height to calculate the donor's body mass index (BMI): TBV=70/(√BMI/ 22) (Lemmens' equation).

In a fifth aspect, the control unit calculates the total blood volume (TBV) of the donor based on the donor's weight (Wt), height (Ht) and gender (male or female), and in the case of a male, TBV=(0 .3669 x Ht ³ ) + (0.03219 x Wt) + 0.6041, for women TBV = (0.3561 x Ht ³ ) + (0.03308 x Wt) + 0.1833, where the unit of Ht It is programmed to calculate so that Wt is in meters and Wt is in kilograms (Nadler's formula).

In a sixth aspect, a volume of plasma is produced such that a target volume (TVP) of pure plasma in the plasma product is determined based on donor unique characteristics consistent with donor safety and comfort. A method is provided for performing plasmapheresis to collect blood (i.e., anticoagulated plasma, VPP). In particular, the target volume (TVP) of pure plasma collected is based on the donor's weight, or weight and height.

In a seventh aspect, the target volume of pure plasma (TVP) collected may be a multiple of the donor's body weight. Alternatively, TVP may be a multiple of the donor's total blood volume TBV, where the donor's TBV is determined based on the donor's weight and height using established methodologies such as the Lemmens equation or Nadler's formula. Ru.

The target volume of plasma product collected (TVPP) is based on the target volume/weight of pure plasma and the percentage of anticoagulant AC in the plasma product (% _ACTVPP ): TVPP=TVP/(1 -%AC _TVPP ). Here, %AC _TVPP is based on the AC ratio (ACR) and the donor's hematocrit.

Once the TVPP is determined, a plasmapheresis procedure is initiated in which whole blood is collected from the donor, mixed with an anticoagulant in a specific ratio, and then separated into plasma, red blood cells, and other cellular components. Once TVPP has been collected, as determined by a scale associated with the plasma collection container, whole blood collection from the donor is stopped and red blood cells and other cellular components are returned to the donor.

In a seventh aspect, in determining the target volume of plasma product to be collected, the donor's hematocrit is determined prior to the collection phase of each cycle, either by calculation or by a signal, such as from a sensor, indicating the donor's hematocrit. It can be determined based on Additionally, the amount of plasma product within the plasma collection container can be determined, for example, by a gravimeter associated with the plasma collection container or an optical sensor that directly measures volume.

In another aspect, a method for operating a plasma exchange system to collect a plasma product volume that includes a maximum allowable volume/weight of raw plasma according to limits set in an FDA nomogram based on donor weight is provided. provided.

To collect the maximum volume/weight of raw plasma allowed by the FDA nomogram, utilize the donor's hematocrit to create a target volume of plasma product with the maximum volume of raw plasma allowed by the FDA nomogram. / A modified nomogram is provided to calculate the weight. The calculated raw plasma volume/weight is compared to the maximum raw plasma volume/weight allowed by the FDA nomogram. If the calculated raw plasma volume/weight is less than the maximum allowable volume/weight, the collected plasma product volume/weight will be less than the maximum plasma product volume/weight allowed by the FDA nomogram. is also adjusted upward by an amount equal to the difference plus the additional amount of anticoagulant added to process the additional volume/weight of plasma.

Therefore, knowledge of the donor's hematocrit and instrument AC ratio is used to determine the volume of additional raw plasma that can be safely collected from the donor consistent with the limits set forth in the FDA nomogram, and then The total volume/weight of plasma product collected is adjusted accordingly based on the donor's body weight as described in .

Typically, plasmapheresis procedures involve successive cycles of alternating stages, in which whole blood is drawn from a donor and plasma is separated and collected. In the other step, the separated red blood cells and any other non-RBC cell components are returned to the donor. The donor's hematocrit changes during the course of the plasmapheresis procedure, thus affecting the amount of anticoagulant in the plasma product collected from one cycle to the next.

Accordingly, in a first aspect of the present disclosure, a new hematocrit value of the donor is determined prior to initiation of the subsequent extraction/separation step to ensure that the maximum amount of raw plasma allowed by the FDA nomogram is collected. The target volume/weight of the plasma product of the procedure is recalculated before the start of each extraction/separation step to ensure that

In another aspect, additional methods are provided for collecting a volume of plasma during an apheresis procedure. The steps of the method include determining the total whole blood volume of the donor, V _b , determining the volume of raw plasma (V RP ) that can be collected from the donor based on V _b , and determining the volume of raw plasma (V _RP ) that can be collected from the donor, and the plasma production that will be collected. (V _PP ), where V _PP is the volume of raw plasma (V _RP ) to be collected plus the volume of anticoagulant (V RP ) added to the V _RP during the apheresis procedure. V _AC ), and V _PP =V _RP ×K, where K=(ACR×(1-Hct/100)+1)/(ACR×(1-Hct/100)). Yes, the anticoagulant ratio (ACR, defined for donor blood without anticoagulants as the ratio of the volume of donor blood to the volume of anticoagulant to donor blood) established for the procedure and the donor Hct based on the following steps: collecting whole blood from a donor, adding an amount of anticoagulant to the whole blood consistent with the ACR, separating plasma products from the whole blood, and separating the plasma products in a collection container. and transferring plasma product to a collection container until the volume reaches _VPP . Because the plasmapheresis procedure consists of multiple extraction/separation steps and return steps, the V _PP of the procedure is based on the value of the donor's hematocrit determined before the start of each extraction step and the plasma adjusted accordingly. Based on the target volume of product, it is recalculated before each extraction/separation stage is started. Alternatively, V _RP may be determined based on a calculation of the donor's total plasma volume based on V _b and the donor's hematocrit.

In another aspect, a method is provided for determining the volume of plasma product (V _PP ) that can be collected during an apheresis procedure. Here, V _PP is equal to the volume of raw plasma that can be collected (V _RP ) plus the volume of anticoagulant added to V _RP during the apheresis procedure (V _AC ). The steps of this method include determining the donor's weight (W _kg ) and gender (male or female), determining the donor's hematocrit (Hct), and determining the donor's weight (W _kg ) and gender (male or female). Determining the volume of raw plasma (V _RP ) that can be collected based on and the ratio K between V _PP and V _RP based on the anticoagulant ratio (ACR) and donor Hct: This includes determining V PP such that K=V _PP /V _RP and determining V _PP such that V _PP =V _RP ×K. Further, K=(ACR×(1−Hct/100)+1)/(ACR×(1−Hct/100)). After the V _PP is determined, whole blood is collected from the donor, anticoagulant is added to the whole blood in an amount consistent with the ACR, the plasma product is separated from the whole blood, and the plasma product is transferred to a collection container. It will be done. After the desired amount of whole blood has been collected from the donor, the red blood cells are returned to the donor. Next, the donor's Hct and _VPP are determined before each harvest step.

In a related aspect, the collection and separation steps are repeated until the volume of plasma product in the collection container reaches _VPP .

In a related aspect, the donor's hematocrit after the first collection step is such that the donor's red blood cell volume is the same at the beginning of each collection cycle, while the total volume of blood collected is the same from one cycle to the next. It can be calculated by volume balance, assuming that it is reduced by an amount equal to that of raw plasma. Alternatively, the donor's hematocrit at the beginning of each collection cycle can be measured with an optical or other sensor.

In a further aspect, the volume of raw plasma that can be collected from a particular donor can be determined by any one of several different means. Such measures include, for example, FDA nomograms that only take into account the donor's body weight, a modified version that additionally takes into account the donor's hematocrit, and a portion of the total blood volume or total plasma volume calculated for a particular donor. Contains FDA nomograms. Total blood volume or total plasma volume can be calculated using, for example, Nadler's equation, Gilcher's rule, tables provided by the International Council for Standardization in Hematology (ICSH), or other methods using the donor's height, weight, sex, and age. It can be determined using generally accepted methods and consistent with donor safety and comfort.

In another aspect, an automated system for separating plasma from whole blood is provided that includes reusable hardware components and a disposable kit. The disposable kit further comprises: i) a separator for separating whole blood into a plasma fraction and an enriched cell fraction, to which is integrally connected a blood line for transporting the whole blood from the donor to the separator; a separator having an input, a plasma output port integrally connected to the plasma collection container by a plasma line, and a concentrated cell integrally connected to a reservoir for receiving the concentrated cells prior to reinfusion into the donor. an exit port; ii) a donor line terminating in a venipuncture needle for transporting whole blood from the donor to the blood line; and iii) an anticoagulant integrally connected to the blood line for transporting anticoagulant to the donor line. an anticoagulant line configured to be connected to a source of coagulant; and iv) a reinfusion line for transporting the concentrated cells from the reservoir to the donor line.

The reusable hardware components further include: i) a first peristaltic pump for delivering anticoagulant at a controlled rate to the blood line during the collection phase; and ii) anticoagulated during the collection phase. iii) a second pump for delivering the collected whole blood to the separator and returning the concentrated cellular components during the reinfusion phase; and iii) delivering the concentrated cellular components from the separator to the reservoir during the collection phase. iv) a clamp associated with each of the blood line, plasma line, and reinfusion line; and v) a third pump for measuring the weight of each of the plasma collection container, reservoir, and anticoagulant source. vi) a programmable control comprising a touch screen for receiving input from an operator, the programmable control receiving signals from each of the weigh scales and vi) a programmable control having a touch screen for receiving input from an operator; automatically operating the pump, a second pump, and a third pump and clamp to separate the whole blood into a plasma fraction and an enriched cell fraction during a collection phase and returning the enriched cells to the donor during a reinfusion phase; It is configured as follows. The programmable control further determines a target amount of plasma product to be collected in the plasma collection container according to any of the embodiments described herein, such that the amount of plasma product in the plasma collection container is controlled. and is configured to terminate the collection phase upon receiving a signal equal to a target amount of plasma product determined by the department. In determining the target amount of plasma product to be collected, the controller may be configured to calculate the donor's hematocrit before the collection phase of each cycle. Alternatively or additionally, the controller may receive a signal from a sensor or the like indicative of the donor's hematocrit. Additionally, the amount of plasma product in the plasma collection container can be determined, for example, by a gravimeter associated with plasma collection or an optical sensor that directly measures volume.

FIG. 1 is a perspective view of an exemplary plasmapheresis device suitable for use with the systems and methods of the present application.

FIG. 2 is a perspective view of a rotating membrane separator of the type incorporated in a disposable set that can be used in the plasma exchange system of FIG. 1, with portions cut away to show details.

3 is a perspective view of the front panel of the plasma exchange system of FIG. 1 showing the components of the disposable set attached thereto; FIG.

FIG. 4 is a schematic diagram illustrating the operation of the plasmapheresis system during the collection phase.

FIG. 5 is a schematic diagram illustrating the operation of the plasmapheresis system during the reinfusion phase.

Figures 6a and 6b are flowcharts illustrating the steps of the method used in the present application to collect a target volume of pure plasma.

FIG. 7 is a table showing the volume of pure plasma based on donor hematocrit that is within the plasma product volume limits set by the FDA nomogram using a 1:16 ratio of anticoagulant to whole blood. .

Figure 8 shows the volume of "unclaimed" pure plasma in the plasma product based on the difference between the values shown in Figure 7 and the maximum volume of pure plasma that can be collected based on the FDA nomogram. This is a table showing.

FIG. 9 is a table showing the volume of plasma product that can be collected from a donor based on the donor's weight and hematocrit, resulting in the maximum allowable volume of pure plasma allowed by the FDA nomogram.

FIG. 10 is a table showing inputs to a programmable control for performing a hypothetical plasmapheresis procedure according to the method of the present application.

Figures 11a and 11b illustrate how the donor's hematocrit would increase over the course of a hypothetical plasmapheresis procedure based on the input from the table in Figure 10, resulting in the increase in the donor's hematocrit needed to collect the target volume of pure plasma. Contains a table divided into two parts showing how the total collected volume of plasma product increases.

FIG. 12 is a graph showing IgG dilution during plasmapheresis.

A more detailed description of systems and methods according to the present disclosure is provided below. It is to be understood that the following descriptions of particular apparatus and methods are for illustrative purposes and are not exhaustive of all possible variations or applications. Accordingly, the scope of the present disclosure is not intended to be limiting, but should be understood to include variations or embodiments that would occur to those skilled in the art. Various aspects of the systems and methods are described in further detail in US Patent Application Publication No. 2020/0147289, which is incorporated herein by reference.

In the context of this application, plasmapheresis is performed on an automated system comprising a hardware component, generally designated 10, and a disposable set, generally designated 12, for collecting plasma to be treated as source plasma. is executed. With reference to FIGS. 1-5 and described in more detail below, the disposable set 12 includes integrally connected separators, containers, and tubing for transporting blood and solutions within a sterile fluid pathway. Become.

Separator 14, best shown in FIG. 2, has a rotating membrane filter 16 mounted on a rotor 18 that rotates within case 20 to separate blood into its components. A detailed description of rotating membrane separators is provided in Schöndorfer US Pat. No. 5,611,113, which is incorporated herein by reference. As will be appreciated, in other systems, separation of whole blood may be accomplished by centrifugation. See, eg, US Pat. No. 5,360,542 to Williamson et al.

During plasmapheresis, anticoagulated whole blood enters separator 14 through whole blood input port 22. Plasma is separated by a rotating membrane filter, exits plasma output port 24 and enters plasma collection container 28 through plasma line 26 . The concentrated cells are pumped from the concentrated cell output port 30 into the reservoir 32, where they remain until reinfused into the donor.

The disposable set 12 also includes an anticoagulated tubing line (donor line 34 terminating in a venipuncture needle 36) for introducing whole blood from the donor into the system during collection and returning concentrated cells to the donor during reinfusion. A tubing line that transports whole blood to the separator (blood line 38), a tubing line that transports the concentrated cells to the reservoir (cell line 40), and a tubing line that transports the concentrated cells from the reservoir to the donor line (reinjection line 42). ), a tubing line that transports plasma to the plasma collection container (plasma line 44), a tubing line that transports saline (saline line 46), and a tubing line that transports anticoagulant (AC line 48). include.

Hardware components 10 include a programmable control 50 and a touch screen 52 with a graphical user interface ("GUI") for operator control of the procedure. For example, the GUI displays donor ID, donor gender, donor height, donor weight, donor age, donor hematocrit/hemoglobin, target saline infusion volume (if saline protocol is selected), and target Allow any input of plasma volume. Touch screen 52 also allows the operator to gather status information and handle error conditions.

Three peristaltic pumps are located on the front panel of hardware component 10, including AC pump 54, blood pump 56, and cell pump 58. AC pump 54 delivers anticoagulant solution (AC) at a controlled rate into blood line 38 as whole blood enters the set from a donor. Blood pump 56 pumps anticoagulated whole blood to the separator during the collection phase of the procedure and returns concentrated cellular components and optional replacement fluid to the donor during the reinfusion phase of the procedure. Cell pump 58 delivers concentrated cellular components from separator 14 to the reservoir during the collection phase.

The front panel also includes four clamps to which tubing from the disposable set 12 is attached, including a reinfusion clamp 60, a blood clamp 62, a saline clamp 64, and a plasma clamp 66. The reinfusion clamp 60 closes during the collection phase (FIG. 5) to block the reinfusion line (42) and opens during the reinfusion phase (FIG. 5) to allow the blood pump to transfer concentrated cellular components from the reservoir 32 to the donor. to be able to be re-injected. Blood clamp 62 opens during the collection phase to allow anticoagulated whole blood to be delivered to separator 14 and closes during the reinfusion phase to block blood line 38. Saline clamp 64 closes to block saline line 46 during the collection phase and reinfusion of separated cellular components. If saline is used as the replacement fluid, the saline clamp 64 opens during the reinfusion phase. Plasma clamp 66 opens during the collection phase to allow plasma to flow into plasma collection container 28 and closes during the reinfusion phase.

Hardware component 10 includes three gravimeters for monitoring current plasma collection volume (gravimeter 68), AC solution volume (gravimeter 70), and concentrated intracellular volume (gravimeter 72). include. The system also includes various sensors and detectors, including a venous pressure sensor 74, a separator pressure sensor 76, an optical blood detector 78, and an air detector 80.

The donor is connected to the system throughout the procedure. As shown, the disposable set 12 includes a single venipuncture needle 36 through which whole blood is drawn from the donor during a collection phase (FIG. 4) and a reinfusion phase (FIG. 5). The enriched cells are returned to the donor. As mentioned above, the plasmapheresis procedure involves multiple cycles, each cycle having a collection/separation step followed by a return or reinfusion step. During the collection phase, whole blood is separated into plasma and concentrated cells. The disposable set includes a plasma collection container 28 for receiving separated plasma and a reservoir 32 for receiving concentrated cells. In the reinfusion phase, concentrated cells from reservoir 32 are reinfused into the donor through venipuncture needle 36. Plasma exchange performed using a single venipuncture needle 36 may involve multiple cycles of collection and reinfusion.

Returning to FIG. 4, during the collection phase, anticoagulant solution (AC) is pumped at a controlled rate and mixed with the whole blood entering the disposable set 12. The anticoagulated blood is sent to separator 14 where plasma is separated from cellular components and sent to plasma collection container 28.

Cellular components are pumped from separator 14 to reservoir 32 . The collection phase stops when the reservoir 32 reaches the expected volume of concentrated cells or when the target plasma collection volume is achieved.

Next, the reinjection phase begins. Referring to FIG. 5, during the reinfusion phase, blood pump 56 reverses direction and pumps concentrated cells from reservoir 32 through apheresis needle 36 back to the donor. If the saline protocol is selected, saline is returned to the donor as a replacement fluid for the collected plasma, and saline is infused after the final reinfusion step.

The automated plasma collection device collects the volume/weight of anticoagulated plasma (i.e., plasma product) with the maximum volume/weight of raw plasma allowed by the donor within the limits set by the FDA nomogram. is configured to do so. To maximize the volume of raw plasma that makes up the plasma product, the device is programmed with a nomogram that takes into account the donor's hematocrit. Knowing the donor's hematocrit and the AC ratio of the device determines the maximum raw plasma fraction that can be collected from the donor consistent with the total raw plasma volume/total weight limits listed in the FDA nomogram. The total volume/weight of plasma product collected can be determined such that the volume/weight is included in the plasma product. By programming the calculations into the control, the potential for operator error is reduced compared to calculating collection volumes off-line and inputting them into the device.

During plasmapheresis, when the anticoagulant is mixed with the whole blood taken from the donor, the anticoagulant is evenly distributed within the pure/raw plasma of the blood. However, the volume of pure/raw plasma in whole blood depends on the hematocrit (Hct) of the whole blood. The following relationships are established.
Volume of red blood cells = Volume of whole blood x Hct/100 [1]
Volume of pure/raw plasma = Volume of whole blood x (1-Hct/100) [2]
When the anticoagulant is mixed with whole blood, it is measured at an AC ratio (ACR) of 16 parts whole blood to 1 AC, or 1 part whole blood to 0.06 parts AC.
ACR=volume of whole blood/volume of anticoagulant (donor blood does not contain anticoagulant) [3]
(This yields slightly different results than the FDA nomogram, which, as mentioned above, has an anticoagulant to anticoagulated blood ratio of 1:16, or an anticoagulant of 0.06 (The volume of anticoagulant that can be added to one part of anticoagulated blood is standardized.)
Volume of anticoagulated blood = volume of anticoagulant + volume of whole blood [4]
Combining the equations gives us the following:
Volume of pure/raw plasma = ACR x volume of anticoagulant x (1-Hct/100) [5]
The red blood cells are returned to the donor, so:
Volume of plasma product collected = Volume of pure/raw plasma + Volume of anticoagulant [6]
Equations [5] and [6] can be combined to calculate the amount of anticoagulant in a given amount of collected plasma.
Volume of anticoagulant = Volume of plasma product collected/(1+ACR×(1-Hct/100)) [7]
moreover,
Volume of plasma product collected = Volume of pure/raw plasma x K, where K = (ACR x (1-HCT/100) + 1)/(ACR x (1-HCT/100)) [8]

Considering the relationship expressed in the above equation, the volume of pure/raw plasma contained within the volume of plasma product allowed under the FDA nomogram can be determined based on the donor's hematocrit. . The results of such calculations are shown in FIG. FIG. 7 shows the volume of pure/raw plasma based on the donor's hematocrit that is within the plasma product volume limits set by the FDA nomogram.

As can be seen with reference to Figure 7, if the donor's weight is between 110 and 149 pounds (maximum plasma product volume according to the FDA nomogram is 690 mL), if the donor's hematocrit is 42 or higher, the The volume of raw plasma used is less than the 625 mL allowed by the FDA nomogram. If the donor's hematocrit is 40 or higher, if the donor weighs 150-174 lbs (maximum plasma collection volume by FDA nomogram is 825 mL), if the donor weighs 175 lbs or more (maximum plasma collection volume by FDA nomogram is 880 mL) The situation is similar.

The table shown in Figure 8 shows the "claims" in plasma product based on the difference between the values shown in Figure 7 and the maximum volume of pure/raw plasma that can be collected based on the FDA nomogram. "Unprocessed" indicates the volume of raw plasma. Therefore, as shown in the table shown in Figure 9, the plasma product collected from a particular donor varies from what is listed in the FDA nomogram to the "unclaimed" pure/unclaimed product listed in Figure 8. The amount can be adjusted to correspond to the amount of plasma being processed plus the amount of anticoagulant needed to process the additional volume.

Alternatively, the volume of plasma product collected can be determined by first determining the donor's weight and hematocrit (Hct), and then determining the volume of raw plasma that can be collected ( _VRP ) based on the donor's weight (W _kg ). and based on the anticoagulant ratio (ACR; 1:16 or 0.06:1 according to the FDA nomogram) and donor Hct, the ratio of V _PP to V _RP such that K=V _PP /V _RP . It can be calculated by determining the ratio K between and determining V _PP such that V _PP =V _RP ×K. Further, K=(ACR×(1−Hct/100)+1)/(ACR×(1−Hct/100)).

In yet another method, the volume of plasma product collected (V _PP ) can be collected based on donor body weight (W _kg ) by first determining donor body weight (W _kg ) and hematocrit (Hct). Determine the volume of raw plasma (V _RP ) and calculate the volume of anticoagulant added based on the anticoagulant ratio (ACR; 1:16 or 0.06:1 according to the FDA nomogram) and donor hematocrit. (V _AC ) is calculated by determining V _AC = V _RP × (ACR × (1-Hct/100)) and determining the collection volume such that V _PP = V _RP + V _AC . obtain.

In accordance with one aspect of the present disclosure, an automated plasma collection device generates a plasma product (pure plasma + anticoagulant) having a volume/weight of pure plasma allowed to the donor as determined by any of the details described below. ) is configured to collect the volume/weight of

Referring to Figure 6a, a first method (70) for collecting a target volume of plasma product (TVPP) is shown. In this method, the target volume of plasma product (TVPP) is calculated by first calculating the target volume of pure plasma (TVP) to be collected based on the donor's weight (step 72) and then determined by determining the percentage of anticoagulant (%AC _TVPP ) in the target volume of plasma product collected based on the agent ratio (ACR) and the donor's hematocrit, where TVPP=TVP/(1- % _ACTVPP ) (Step 74). Although this method does not require intervening calculations of either the donor's total blood volume or total plasma volume before determining the target collection volume of donor plasma, alternative embodiments include such calculations. You can.

Various methods can be used to determine the target volume of pure plasma that can be collected directly from the donor's weight. For example, the donor's weight may be multiplied by an established constant “K ₁ ” (such as 10 mL/kg). Alternatively, donor weight may be divided into weight categories or weight ranges (e.g., at least 3 categories, at least 6 categories, etc.) and a fixed volume set for each category (e.g., according to the FDA nomogram discussed above). The donor weight range is divided into three categories).

Anticoagulant ratio (ACR) can be defined in one of two different ways. In the first method, ACR is the ratio of the volume of whole blood to the amount of anticoagulant (ACR=WB/AC). In the second method, ACR is the ratio of whole blood volume plus anticoagulant volume to anticoagulant volume (ACR=(WB+AC)/AC). If ACR=WB/AC, the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) is determined according to the following equation: %AC _TVPP = 1/(1+ACR(1-Hct)), ACR and Hct are expressed as percentages. If ACR=(WB+AC)/AC, the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) is determined according to the following equation:
%AC _TVPP = 1/(1+(ACR-1)(1-Hct)) ACR can be expressed as either a ratio or a percentage, ranging from 7:1 to 20:1, or about 5% to 14%. It changes with An exemplary ACR is 16:1, or 6.25%.

Returning to FIG. 6a, once the TVPP has been determined as described above, whole blood is collected from the donor (step 76) and mixed with an anticoagulant based on a predetermined ratio ACR (step 78). The anticoagulated whole blood is then introduced into separator 14 where it is separated into plasma and concentrated (red blood cell) cells (step 80). Plasma products (pure plasma and anticoagulant) are collected in plasma collection container 28 (step 82) and separated red blood cells are collected in reservoir 32. When the plasma product is collected, the volume of plasma product (pure plasma and anticoagulant) in the plasma container, VPP, is determined (step 84). When VPP equals the target volume of plasma product (TVPP), whole blood collection is stopped and remaining blood components (such as red blood cells) are returned to the donor (step 86).

Referring to FIG. 6b, a second method (90) for collecting a target volume of plasma product TVPP is shown. In this method, the target volume of plasma product (TPPV) is determined by first calculating the donor's total blood volume (TBV) based on the donor's weight and height (step 92) and then determining the target volume of pure plasma to be collected. (TVP) is calculated as a percentage of TBV (step 94) and based on the predetermined anticoagulant ratio (ACR) and hematocrit, the percentage of anticoagulant in the target volume of plasma product collected (% AC _TVPP ) (step 96) and TVPP=TVP/(1-%AC _TVPP ) (step 98). %AC _TVPP can be determined as described above in connection with the first method. In this method, there is no need to calculate the donor's total plasma volume to determine the target collection volume of donor plasma.

The donor's plasma volume can be estimated based on the donor's total blood volume, and the volume of plasma that can be collected consistent with donor safety and comfort may be based on this estimate. Methods that utilize donor parameters are commonly used to estimate the donor's total blood volume. The donor's total blood volume can be calculated using the Lemmens equation (which uses the donor's body mass index to determine total blood volume), the Nadler equation (which takes into account the donor's height, gender, and weight), and the Gilcher rule (which takes into account the donor's height, gender, and weight). , body weight, morphology (obese, thin, normal, or muscular)) or the International Council for Standardization of Hematology ("ICSH") as described in British Journal of Hematology 1995, 89:748-56. ) standards (taking into account the donor's height, weight, age, and gender). Other methods for determining a donor's total blood volume can also be used. In another embodiment, multiple such methods can be used and an average, intermediate, or weighted average of the methods can be taken as the total blood volume of the donor. For example, once the donor's total blood volume is determined, the donor's plasma volume can be estimated by multiplying the total blood volume by the constant " _K2 ." Here, K ₂ is equal to (1-donor Hct).

Pearson et al., “Interpretation of measured red cell mass and plasma volume in adults: Expert Panel on Radionuclides of the International al Council for Standardization in Haematology (Interpretation of red blood cell and plasma volumes measured in adults: International Council for Standardization in Haematology) Gender, age, height, weight, and pregnancy data as described in the Expert Panel on Nuclides), British J. Haematology, 89:748-756 (1995) (where the formula recommended by ICSH was derived); From analysis of demographic, laboratory, and laboratory data from the 2015-2016 National Health and Nutrition Examination Survey, from which hematocrit and hematocrit values were extracted, donors with specific characteristics (i.e., underweight women with high hematocrit values) It has been confirmed that up to 36% of the available plasma can be collected within current regulations. Such donor plasma exchange methods are routinely performed without side effects; It is considered safe, suggesting that up to 36% of a donor's available plasma can be safely collected by plasmapheresis.

Given that only a negative deviation of the donor's true blood volume from the predicted/calculated total blood volume presents a potential risk, further adjustment downwards to the harvestable volume of plasma is appropriate. It can be. Based on the consideration of deviations between calculated blood volumes as determined by Pearson et al. cited above.

Therefore, the donor's total blood volume (TBV) may be calculated based on the donor's weight (Wt) and height (Ht), and the donor's body mass index such that TBV=70/√(BMI/22) (BMI) can be calculated. Here, BMI=Wt/Ht ² , the unit of Ht is meter, and the unit of Wt is kilogram (Lemens equation). See "Estimation of Blood Volume in Obese and Morbidly Obese Patients", Lemens et al., Bariatric Surgery 16, 2006, pages 773-776.

Alternatively, the donor's total blood volume (TBV) is based on the donor's weight (Wt), height (Ht) and gender (male or female): TBV = (0.3669 x Ht ³ ) + (for males) 0.03219 x Wt) + 0.6041, for women TBV = (0.3561 x Ht ³ ) + (0.03308 x Wt) + 0.1833, where Ht is in meters and Wt is in kilograms. (Nadler's formula), can be calculated as follows.

The percentage by which TBV is multiplied to obtain TVP (and ultimately TVPP) is chosen to maximize the volume of pure plasma collected from the donor consistent with donor comfort and safety. Percentage ranges in various embodiments can vary, such as about 1% to 15%, at least 15%, less than 18%, about 15% to 17%, about 12%, about 16% or about 18% of TBV. The TVPP may be subject to a maximum collection volume of, for example, 1000 mL or 1050 mL, regardless of the TBV of the donor.

Adjust (V _C ) to the calculated volume of whole blood TBV before calculating the target volume of pure plasma TVP = 0.36 (1-Hct) (TBV-V _C ) where V _C =523 mL. Based on regression analysis of experimental blood volume data described in Retzlaff et al., "Red Blood Cell Volume, Plasma Volume, and Lean Body Mass in Adult Men and Women," Journal of Hematology, 33, 5: 649-667 (1969). ing. There is 95% confidence that the predicted blood volumes of individuals differ by no more than 20.5%. Therefore, a scaling factor of 0.795 can be applied to determine the harvestable raw plasma to be 36% of the total plasma volume of the above donor. This yields 28.6% of the donor's calculated raw plasma volume, meeting donor safety and comfort.

Returning to FIG. 6b, once the TVPP has been determined as described above (based on TBV), whole blood is collected from the donor (step 100) and mixed with an anticoagulant based on a predetermined ratio (step 100). 102). The anticoagulated whole blood is then introduced into separator 14 where it is separated into plasma and concentrated (red blood cell) cells (step 104). Plasma products (pure plasma and anticoagulant) are collected in plasma collection container 28 (step 106) and separated red blood cells are collected in reservoir 32. When the plasma product is collected, the volume of plasma product VPP (pure plasma and anticoagulant) in the plasma container is determined (step 108). When VPP equals the target volume of plasma product (TVPP), whole blood collection is stopped and remaining blood components (such as red blood cells) are returned to the donor (step 110).

Therefore, the collection volume (volume of plasma product) is determined based on the volume of raw plasma volume that can be collected from a particular donor, the donor's hematocrit, and a fixed anticoagulant ratio (ACR). As a result, this method allows for more consistent control of the donor's raw plasma volume, the variable most relevant to donor safety.

In an exemplary method, an operator inputs a collection volume of plasma product for a particular donor into the system control based on a target volume of raw plasma that can be collected. The target plasma collection volume can be as shown in FIG. 9 based on the donor's weight and hematocrit at the initial collection stage, or by any of the other methods described above. Alternatively, the controller may determine, for example, the donor's weight and hematocrit, and/or the donor's total blood volume, total plasma volume, and methodology used to determine the target volume of plasma that can be collected. The target plasma product collection volume for the initial collection phase is set according to the method described above when the operator enters any of the additional donor-specific information (e.g., donor gender, height, and age) requested by configured to calculate.

In practice, the operator inputs the collection volume of plasma product for a particular donor into the system control based on the target volume of raw plasma that can be collected. The target plasma collection volume can be as shown in FIG. 9 based on the donor's weight and hematocrit at the initial collection stage, or by any of the other methods described above. Alternatively, the controller may include, for example, the donor's weight and hematocrit, and/or the donor's total blood volume, total plasma volume, and methodology used to determine the target volume of plasma that can be collected. The target plasma product collection volume for the initial collection phase is set according to the method described above when the operator enters any of the additional donor-specific information (e.g., donor gender, height, and age) requested by configured to calculate.

Preferably, the system administrator provides an indication whether the target collection volume of plasma product (TVPP) is to be determined by the system (e.g., according to one of the methods described above) or entered directly into the system by the operator. Set first. If the operator enters the TVPP, the system administrator disables the control's ability to calculate the TVPP. The system administrator also sets the AC ratio used in all procedures. If the controller determines the TVPP, the administrator may enable appropriate donor-specific characteristics to be entered into the controller, either by the operator or the donor administrator, for calculating the TVPP according to any of the methods described above. Set up your system. The system allows donor parameters used for eligibility screening (weight, height, hematocrit, etc.) to be electronically transmitted to the instrument, thereby avoiding operator errors in inputting donor parameters. The donor management system can also utilize donor screening measurements, along with the relationship between pure plasma volume and collection volume, to automatically calculate the TVPP to send to the plasmapheresis machine control. Otherwise, the controller calculates TVPP before collection of whole blood from the donor begins. Additionally, when the controller/donor management system calculates TVPP, the administrator configures the system to allow the operator to enter TVPPs other than the calculated volume. Additionally, the system allows the operator to extract the calculated TVPP from the calculated TVPP before or during the procedure, for example, if there is a need to reduce the estimated time to perform/complete the procedure for reasons of donor comfort or convenience. Make it possible to change TVPP. Upon completion of the procedure, the actual volume of pure plasma collected and the target volume of plasma (TPV), as well as the actual volume of collected plasma product (VPP), and the target volume (TVPP) are displayed. be done.

As mentioned above, the plasmapheresis procedure may be performed in multiple cycles of collection/harvesting and return/reinfusion phases. If the return/reinfusion step does not include reinfusion of replacement fluid, the donor's hematocrit will increase with each cycle. Therefore, if the target volume of plasma product is determined based only on the donor's initial hematocrit value and does not take into account the donor's increasing hematocrit value, then the initial calculation to determine the target volume of plasma product will The percentage of anticoagulant in the plasma product will be higher (and the volume of raw plasma will be lower) than in the plasma product. Therefore, to ensure that the volume of plasma product collected contains the maximum volume of raw plasma determined to be collected from a particular donor, the target volume of plasma product is is recalculated periodically throughout the plasmapheresis procedure, such as before the start of the collection phase of each cycle, to account for changes in hematocrit values.

Therefore, a determination of the target volume of plasma product is made based on the donor's initial hematocrit value. The plasmapheresis procedure begins with a first collection phase until a specified volume of whole blood (usually about 500 mL) is collected from the donor. An anticoagulant is added to the whole blood and the anticoagulated whole blood is separated into plasma products, red blood cells, and other non-RBC blood components. At the end of the first collection phase, the red blood cells and non-RBC blood components are returned to the donor. The current volume of plasma product collected after the initial collection step is determined, for example, by a gravimeter. Next, the current value of the donor's hematocrit is established, a new target volume of plasma product to be collected is determined, and a second cycle of collection and return phases is performed. The cycle of collection and return phases is repeated until the target volume of plasma product for the plasmapheresis procedure is collected, as recalculated before the start of each collection stage. After the final collection phase, the controller initiates the final red blood cell reinfusion phase, after which the donor is disconnected.

The advantages of performing a plasmapheresis procedure with multiple collection/reinfusion cycles according to the above methodology can be seen by referring to FIG. 10 and the tables in FIGS. 11a, 11b. FIG. 10 shows input data for a hypothetical plasmapheresis procedure for a donor who weighs 190 pounds (86.4 kg) and has an initial hematocrit of 44. Referring to the table in FIG. 1, the simplified FDA nomogram limits the volume of plasma collected from such donors to 800 mL and the total collection volume of plasma product to 880 mL. In this example, the FDA nomogram limitations on the volume of raw plasma that may be collected are for illustrative purposes only. As mentioned above, other methodologies can be used to determine the amount of raw plasma that may be safely extracted from a donor different from that indicated by the FDA nomogram.

The number of collection and reinfusion cycles in a plasmapheresis procedure can vary from 3 to 12. In the hypothetical plasmapheresis procedure, there are five collection and reinfusion cycles, which have been chosen for illustrative purposes.

Prior to the start of the first collection cycle, the volume of raw plasma to be collected and the total target volume of plasma product to be collected are determined according to the method described above based on the donor's initial hematocrit value. As shown in the first row of the table (cycle 1 start), the initial target volume of plasma product to be collected is 889 mL, which corresponds to the FDA limit of 800 mL of raw plasma collected from the donor. is the same as shown in the table of FIG. 9 for a donor who weighs 175 pounds or more and has a hematocrit of 44.

During each collection phase, 500 mL of whole blood is collected from the donor to which anticoagulant is added at a predetermined ratio (ie, 1:16), with 31 mL added for each 500 mL collection cycle. Whole blood and anticoagulant are separated into plasma and red blood cell fractions.

During the first return phase (Cycle 1 Return End), red blood cells and "non-RBC" blood components were returned to the donor, so that at the end of the first return cycle, the donor's hematocrit increased to 45.6%. . The amount of red blood cells in the total blood volume remains the same as at the beginning of the procedure, although it is calculated by the control based on the blood volume which is reduced by the amount of raw plasma collected. The controller takes into account the volume of anticoagulant that is re-injected at each return step along with the red blood cells, and the residual anticoagulant in the donor's whole blood collected from cycle 2 onwards, and calculates the amount of anticoagulant for the next cycle. A new hematocrit value can also be determined. The volume of raw plasma collected for the procedure and the total target volume of plasma product are then recalculated based on the donor's newly increased hematocrit and raw plasma volume. This provides a new total target collection volume of 891 mL.

A second collection stage is then performed, resulting in a total of 430 mL of plasma product, including 386 mL of raw plasma collected over the first two collection stages (Cycle 2 Collection End). The red blood cells and "non-RBC" blood components are returned to the donor, after which the donor's hematocrit value is calculated to be 47.2%.

Two further collection stages of 500 mL are performed, each followed by a return stage, in which new values for the volume of raw plasma collected and the total volume of plasma product are determined before the start of each collection stage. be done. As the donor's hematocrit increases, the recalculated target collection volume of the procedure increases to 893 mL (for the third collection stage) and then to 894 mL (for the fourth collection stage). A fifth "mini" collection cycle is performed to increase the volume of raw plasma collected to the 800 mL allowed by the FDA nomogram for the hypothetical donor. The recalculated target collection volume of plasma product for the fifth collection stage remains 894 mL.

Therefore, as shown in the example above, if the target collection volume of plasma product is recalculated for each collection stage, a target collection volume of 894 mL of plasma product is obtained, which corresponds to 800 mL of plasma It is necessary to collect the target volume of processing. In contrast, 889 mL of plasma product would be collected if the target collection volume was determined based solely on the donor's initial hematocrit value, and 880 mL if the target collection volume was based on the simplified FDA nomogram. In both cases, less than the target volume of 800 mL is collected.

As can be appreciated, the greater the accuracy with which a donor's hematocrit can be determined, both before and during treatment, the more the target volume of plasma product collected will be of the maximum volume that can be collected for a particular donor. Likely to contain raw plasma. As mentioned above, the donor's hematocrit during the procedure is such that 100% of the red blood cells drawn in each collection cycle are reinfused in each return cycle, along with 100% of the non-RBC cell product and a volume of anticoagulant. It is based on the assumption that However, it has been confirmed that during the blood separation procedure, interstitial fluid moves into the intravascular space, resulting in the recovery of half of the recovered volume. Saito et al. “Interstitial fluid shifts to plasma compartment during blood donation,” Transfusion 2013;53(11):2744- See 50. The displaced interstitial fluid is added to the red blood cells, non-RBC cell products, and anticoagulant that are reinfused at each return step. Therefore, taking interstitial fluid movement into account will result in a more accurate determination of the hematocrit value and, therefore, a more accurate determination of the target volume of plasma product resulting in the maximum amount of raw plasma. can get.

Interstitial fluid movement during plasmapheresis has been demonstrated by tracking donor immunoglobulin G (IgG) levels over the course of the plasmapheresis procedure. For example, Burkhardt et al., “Immunoglobulin G levels during collection of large volume plasma for fractionation,” Transf. See USION 2017;56:417-420 . If the interstitial fluid has not been displaced, the donor's IgG levels will remain stable throughout the course of the plasmapheresis procedure. However, IgG levels have been shown to decrease, and the amount by which IgG levels decrease is a function of the volume of interstitial fluid moved into the blood system.

Referring to FIG. 12, an empirically developed plot of collected plasma volume (along the X axis versus IgG concentration (along the Y axis)) is shown. A 9% reduction in donor IgG is seen from a baseline of zero plasma collection (at the beginning of the procedure) to 200 mL plasma collection, with an additional 4% reduction from 200 mL to 800 mL collection. This ranges from approximately 9% of the donor's initial total blood volume (after collecting 200 mL of plasma) to an interstitial fluid equal to approximately 13% of the donor's initial total blood volume (after collecting 800 mL of plasma). This is due to the movement of

The following relationship between the amount of donor IgG concentration and the volume of plasma collected was established. y=1.0017x ^−0.02 , where y=IgG concentration and x=plasma volume collected. Therefore, the percentage of donor blood volume replaced by interstitial fluid movement is equal to V _b (1-y). where V _b is the initial volume of donor whole blood. Therefore, the transferred volume of interstitial fluid can be calculated based on the collected plasma volume, and this amount is used at each return step to determine the donor's current total blood volume and hematocrit value. Can be added to the volume of reinfused red blood cells, non-RBC cell products and anticoagulant. As can be seen, the control part automatically determines the volume of interstitial fluid transferred based on the volume of plasma collected and the volume transferred when determining the donor's hematocrit value before each collection step. can be configured to include.

Alternatively, other methods of directly measuring the donor's hematocrit can be used, such as optical sensors, or, if a centrifuge is used, measuring the volume of red blood cells in the centrifuge.

Additionally, anticoagulants are generally introduced into disposable kits in a pre-processing step, such as priming the single-use kit, running one or more pre-cycles, or performing other pre-treatments, before starting the plasmapheresis procedure. be done. Insofar as the anticoagulant used for these purposes is ultimately directed to the plasma product collection container, it is can be taken into account. This could be done, for example, by measuring the weight of a "full" container of anticoagulant and the weight of the container of anticoagulant before the start of the first collection cycle, and adding that volume of anticoagulant to the target volume of plasma product. This can be done by adding: The controller may be configured to automatically perform the steps necessary to account for anticoagulant introduced into the plasma collection container separately from anticoagulated plasma.

The methods and systems described above have several aspects. In a first aspect, a method for collecting plasma is provided in which the plasma product is collected in multiple collection stages during which separated red blood cells are reinfused into a donor. The method of this first aspect comprises: a) determining the volume ( _Vb ) and hematocrit (Hct) of whole blood of the donor; and b) determining the volume of raw plasma ( _VRP ) that can be collected from the donor. and c) determining the volume of plasma product (V _PP ) that can be collected, where the plasma product is the volume of raw plasma plus the volume of anticoagulant. d) collecting whole blood from a donor; e) introducing an anticoagulant at a specific ratio (ACR) into the collected whole blood; and f) converting the collected whole blood into a plasma product. g) collecting the plasma product in a plasma collection container; and h) transferring the red blood cells to the donor after the desired amount of whole blood has been collected from the donor. and i) determining the donor's Hct and _VPP before each collection step.

In a second aspect, steps d) to i) are continued until the measured volume of plasma product in the collection container is equal to V _PP .

In a third aspect, a method for collecting plasma is provided in which the plasma product is collected in multiple collection stages during which separated red blood cells are reinfused into the donor. The method of this second aspect comprises: a) determining the volume of whole blood (V _b ) and hematocrit (Hct) of a donor; and b) the volume of raw plasma that can be collected from the donor based on V _b ( and c) adding to V _RP based on the anticoagulant ratio (ACR) and donor _Hct such that V _AC = V _RP d) determining the volume of plasma product (V _{PP )} that can be collected, where the plasma product is the raw plasma (V _RP ) and the volume of anticoagulant (V _AC ), e) collecting whole blood from the donor, and f) applying the anticoagulant to the collected whole blood at a specific ratio (ACR). g) separating the collected whole blood into a plasma product and a second component comprising red blood cells; h) collecting the plasma product in a plasma collection container; i) after an amount of whole blood has been collected from the donor, returning the red blood cells to the donor; and j) determining the donor's Hct and _VPP before each collection step.

In a fourth aspect, steps d)-j) are continued until the measured volume of plasma product in the collection container is equal to _VPP .

In a fifth aspect, V _b is determined based on one or more donor-specific characteristics including donor weight, height, sex, age, and morphology.

In a sixth aspect, a method is provided for collecting a volume of plasma product (V _PP ) in an apheresis procedure, in which the plasma product is collected in multiple collection stages, during which the plasma product is separated. Red blood cells are reinfused into the donor. In the method of this fourth aspect, the V _PP includes the volume of raw plasma (V _RP ) that can be collected from the donor plus the volume of anticoagulant (V _AC ) that is added to the V _RP during the apheresis procedure. equal to the addition. The steps of the method are: a) determining the donor's weight (W _kg ) and gender (male or female); b) determining the donor's hematocrit (Hct); and c) determining the donor's weight (W _kg) . ) and gender (male or _female ) and d) determining the ratio K between V _PP and V _RP as K=V _PP /V _RP based on the anticoagulant ratio and donor Hct; e) determining V _PP such that V _PP = V _RP ×K; and f) obtaining whole blood from the donor. g) introducing an anticoagulant at a specific ratio (ACR) to the collected whole blood; and h) separating the collected whole blood into a plasma product and a second component comprising red blood cells. i) collecting the plasma product into a plasma collection container; j) returning the red blood cells to the donor after the desired amount of whole blood has been collected from the donor; and k) before each collection step. including determining the donor's Hct and target _VPP .

In a seventh aspect, steps c)-k) are repeated until the measured volume of plasma product in the collection container is equal to _VPP . Preferably, K=V _PP /V _RP =(ACR×(1-Hct/100)+1)/(ACR×(1-HCT/100)).

In an eighth aspect, a method is provided for collecting a volume of plasma product (V _PP ) in an apheresis procedure, in which the plasma product is collected in multiple collection stages, during which the plasma product is separated. Red blood cells are reinfused into the donor. In this fifth aspect, V _PP is the sum of the volume of raw plasma that can be collected from the donor (V _RP ) and the volume of anticoagulant added to V _RP during the apheresis procedure (V _AC ). equal to what was done. The steps of the method are: a) determining the donor's weight (W _kg ) and gender (male or female); b) determining the donor's hematocrit (Hct); and c) determining the donor's weight (W _kg) . ) and donor gender (male or female) and d) determining the volume of raw plasma that can be collected (V _RP ) based on the donor's gender (male or female); and d) determining the volume of raw plasma that can be collected (V _RP ) based on the anticoagulant ratio (ACR) and the donor's Hct. = V _RP × (ACR _× (1-Hct)); and e) determining V _PP so that V _PP = V _RP + _{V AC .} and f) collecting whole blood from the donor; g) introducing an anticoagulant at a specific ratio (ACR) into the collected whole blood; and h) combining the collected whole blood with plasma products and red blood cells. i) collecting the plasma product in a plasma collection container; and j) returning the red blood cells to the donor after the desired amount of whole blood has been collected from the donor. and k) determining the donor's Hct and _VPP before each collection step.

In a ninth aspect, steps d)-k) are continued until the measured volume of plasma product in the collection container is equal to _VPP .

In a tenth aspect, the V _RP is determined by establishing a V _RP for each of a plurality of donor weight ranges and selecting a V _RP for a weight range that includes the donor's weight. Donor weight ranges can be divided into three categories: 110-149 pounds, 150-174 pounds, and 175 pounds and above.

In the eleventh aspect, V _RP =K ₁ ×W _kg .

In the twelfth aspect, V _RP is less than or equal to 28.6% of (1-Hct)×(V _b ).

In a thirteenth aspect, V _b is determined using one of Nadler's equation, Gilcher's five laws, ICSH standards, and other generally accepted methodologies.

In the fourteenth aspect, V _RP =W _kg x 10 mL/kg.

In a fifteenth aspect, when the donor parameters are used to estimate the donor's total blood volume (V _b ), V _RP =K ₂ ×V _b .

In a sixteenth aspect, an automated system for separating plasma from whole blood is provided that includes reusable hardware components and a disposable kit. The disposable kit further comprises: i) a separator for separating whole blood into a plasma fraction and an enriched cell fraction, to which is integrally connected a blood line for transporting the whole blood from the donor to the separator; a separator having an input, a plasma output port integrally connected to the plasma collection container by a plasma line, and a concentrated cell integrally connected to a reservoir for receiving the concentrated cells prior to reinfusion into the donor. an exit port; ii) a donor line terminating in a venipuncture needle for transporting whole blood from the donor to the blood line; and iii) an anticoagulant integrally connected to the blood line for transporting anticoagulant to the donor line. an anticoagulant line configured to be connected to a source of coagulant, and iv) a saline line configured to be attached to a source of saline for transporting saline to the blood line. , and v) a reinjection line for transporting the concentrated cells from the reservoir to the donor line. The reusable hardware components further include: i) a first peristaltic pump for delivering anticoagulant at a controlled rate to the blood line during the collection phase; and ii) anticoagulation treatment during the collection phase. iii) a second pump for delivering the collected whole blood to the separator and returning the concentrated cellular components during the reinfusion phase; and iii) transporting the concentrated cellular components from the separator to the reservoir during the collection phase. a third pump for delivering; iv) a clamp associated with each of the blood line, plasma line, reinfusion line and saline line; and v) each of the plasma collection container, reservoir and anticoagulant source. vi) a programmable control comprising a touch screen for receiving input from an operator, the programmable control receiving signals from each of the scales; , the first pump, the second pump, and the third pump and clamp are operated automatically to separate the whole blood into a plasma fraction and an enriched cell fraction during the collection phase and to enrich the enriched cells during the reinfusion phase. is configured to return to the donor. The programmable control further determines the weight of the plasma fraction collected in the plasma collection container according to any of the embodiments described herein, and is equal to the weight of the plasma fraction determined by the control. The plasma collection container is configured to terminate the collection phase upon receiving a signal from the plasma collection container weigh scale. In determining the target amount of plasma product to be collected, the controller may be configured to calculate the donor's hematocrit before the collection phase of each cycle. Alternatively or additionally, the controller may receive a signal from a sensor or the like indicative of the donor's hematocrit. Additionally, the amount of plasma product in the plasma collection container can be determined, for example, by a gravimeter associated with plasma collection. In one embodiment, the separator includes a rotating membrane separator.

It will be appreciated that the described embodiments are illustrative of some of the applications of the principles of the inventive subject matter. Numerous modifications can be made by those skilled in the art without departing from the spirit and scope of the claimed subject matter, including combinations of features individually disclosed or claimed herein. For these reasons, the scope of the claims should not be limited to the above description, but rather as set forth in the following claims.

Claims (28)

A system for collecting plasma from a donor, the system comprising:
a) a venipuncture needle for collecting whole blood from the donor;
b) a blood separator for separating whole blood into a plasma product and a second blood component comprising red blood cells;
c) a donor line coupled to a venipuncture needle for introducing whole blood from the donor into the blood separator;
d) a first pump for controlling flow through the donor line;
e) an anticoagulant line coupled to an anticoagulant source for mixing the anticoagulant with the whole blood;
f) a second pump for controlling flow through the anticoagulant line;
g) a touch screen for receiving input from an operator;
h) a programmable control unit, the control unit comprising:
determining a target volume of plasma product to be collected (TVPP) based on the donor's weight or based on the donor's weight and height;
determining the percentage of anticoagulant in the target volume of plasma product to be collected (%AC _TVPP ) based on a predetermined anticoagulant ratio (ACR) and donor hematocrit (Hct);
Determine the target volume of pure plasma (TVP) to be collected based on the donor's weight and the plasma product to be collected based on the predetermined anticoagulant ratio (ACR) and donor's hematocrit (Hct) determine the percentage of anticoagulant in the target volume (% _ACTVPP ) of
Here, TVPP=TVP/(1-%AC _TVPP ),
controlling the system to perform a collection and return cycle for collecting whole blood from a donor;
adding an anticoagulant to whole blood at a predetermined ratio (ACR);
separating the anticoagulated whole blood into a plasma product and the second component, and returning the second component to the donor;
Stopping the collection of whole blood from the donor and starting the final return of the second blood component when the measured volume of plasma product in the plasma collection container reaches the target volume of plasma product (TVPP) is configured to
system. 3. The system of claim 2, wherein the controller is further programmed to calculate a target volume (TVP) of pure plasma to be collected as a multiple of the donor's body weight. A system for collecting plasma from a donor, the system comprising:
a) a venipuncture needle for collecting whole blood from the donor;
b) a blood separator for separating whole blood into a plasma product and a second blood component comprising red blood cells;
c) a donor line coupled to the venipuncture needle for introducing whole blood from a donor into the blood separator;
d) a first pump for controlling flow through the donor line;
e) an anticoagulant line coupled to an anticoagulant source for mixing the anticoagulant with the whole blood;
f) a second pump for controlling flow through the anticoagulant line;
g) a touch screen for receiving input from an operator;
h) a programmable control unit, the control unit comprising:
determining the donor's total blood volume (TBV) based on the donor's weight and height;
determining the target volume of pure plasma (TVP) to be collected as a percentage of TBV;
determining the percentage of anticoagulant in the target volume of plasma product to be collected (%AC _TVPP ) based on a predetermined anticoagulant ratio (ACR) and donor hematocrit (Hct);
determining a target volume of plasma product (TVPP);
Here, TVPP=TVP/(1-%AC _TVPP ),
controlling the system to perform a collection and return cycle for collecting whole blood from a donor;
adding an anticoagulant to whole blood at a predetermined ratio (ACR);
separating the anticoagulated whole blood into the plasma product and the second component, and returning the second component to the donor;
When the measured volume of plasma product in the plasma collection container reaches a target volume of plasma product (TVPP), stopping the collection of whole blood from the donor and initiating the final return of said second blood component. configured to start,
system. The controller is further programmed to calculate a total blood volume (TBV) of the donor based on the donor's weight and height for calculating a body mass index (BMI), wherein: 4. The system of claim 3, wherein TBV=70/√(BMI/22) and BMI=weight/ ^height2 . ACR is the ratio of the volume of whole blood to the amount of anticoagulant (ACR = WB/AC),
The controller is further configured to determine the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+ACR(1-Hct)). 4. The system according to claim 1 or claim 3. ACR is the ratio of the volume of whole blood plus the volume of anticoagulant to the volume of anticoagulant (ACR = (WB + AC) / AC),
The controller further determines the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+(ACR-1)(1-Hct)) 4. The system of claim 1 or claim 3, wherein the system is configured to. The controller is further programmed to calculate the donor's total blood volume (TBV) based on the donor's weight (Wt), height (Ht) and gender (male or female); For women, TBV=(0.3669×Ht ³ )+(0.03219×Wt)+0.6041, and for women, TBV=(0.3561×Ht ³ )+(0.03308×Wt)+0. 4. The system of claim 3, wherein the Ht is in meters and the Wt is in kilograms. A method for collecting a target volume of plasma product (TVPP) from a donor, the TVPP comprising, in addition to a target volume of pure plasma (TVP), a volume of an anticoagulant;
a) Determine TVPP by first calculating the target volume (TVP) of pure plasma collected from the donor as a multiple of the donor's body weight, such that TVPP=TVP/(1-% AC _TVPP ); determine the percentage of anticoagulant in TVPP (%AC _TVPP );
where %AC _TVPP is based on anticoagulation ratio (ACR) and donor hematocrit (Hct);
b) collecting whole blood from the donor;
c) mixing an anticoagulant with whole blood at an anticoagulant ratio (ACR);
d) separating anticoagulated whole blood into plasma products, red blood cells, and other cellular components;
e) collecting the plasma product in a container;
f) determining the volume of plasma product (VPP) in said container;
g) if VPP=TVPP, including stopping the collection of whole blood from the donor and returning red blood cells and other cellular components to the donor;
Method. further comprising determining the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+ACR(1-Hct)), where: 9. The method of claim 8, wherein ACR is the whole blood to anticoagulant volume ratio (ACR=WB/AC). Furthermore, determining the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+(ACR-1)(1-Hct)) 9. The method of claim 8, wherein ACR is the ratio of the sum of whole blood volume and anticoagulant volume to anticoagulant volume (ACR=(WB+AC)/AC). Further comprising collecting a target volume of pure plasma (TVPP) in multiple cycles, each cycle comprising a collection phase in which whole blood is collected from the donor and a return phase in which red blood cells and other cellular components are returned to the donor. and the steps;
determining a donor hematocrit (Hct) before said collection step of each cycle; and a target volume of plasma product to be collected based on the donor hematocrit (Hct) determined before said collection step of each cycle. 9. The method of claim 8, comprising recalculating (TVPP). A method for collecting a target volume of plasma product (TVPP) from a donor, the TVPP comprising, in addition to a target volume of pure plasma (TVP), a volume of an anticoagulant;
a) Determine TVPP by first calculating the donor's total blood volume (TBV) based on the donor's weight and height, and calculate the target volume of pure plasma (TVP) to be collected from the donor as a percentage of TBV and determine the percentage of anticoagulant in TVPP (%AC _TVPP ), TVPP = TVP/(1-%AC _TVPP ), where %AC _TVPP is the anticoagulant ratio (ACR) and donor hematocrit (Hct ),
b) collecting whole blood from the donor;
c) mixing an anticoagulant with whole blood at said anticoagulant ratio (ACR);
d) separating anticoagulated whole blood into plasma products, red blood cells, and other cellular components;
e) collecting the plasma product in a container;
f) determining the volume of plasma product (VPP) in said container;
g) if VPP=TVPP, including stopping the collection of whole blood from the donor and returning red blood cells and other cellular components to the donor;
Method. further comprising determining the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+ACR(1-Hct)), where ACR is 13. The method of claim 12, wherein the ratio of whole blood volume to amount of agent (ACR=WB/AC). further comprising determining the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ) such that %AC _TVPP = 1/(1+(ACR-1)(1-Hct)); 13. The method of claim 12, wherein ACR is the ratio of the volume of whole blood plus the volume of anticoagulant to the amount of anticoagulant (ACR=(WB+AC)/AC). further comprising collecting the target volume of pure plasma (TVPP) in multiple cycles, each cycle including a collection phase in which whole blood is collected from the donor and a return phase in which red blood cells and other cellular components are returned to the donor. including
Determine the donor hematocrit (Hct) before the collection phase of each cycle and set the target volume of plasma product (TVPP) to be collected based on the donor hematocrit (Hct) determined before the collection phase of each cycle. 13. The method of claim 12, comprising recalculating . A system for collecting plasma, the system comprising:
a venipuncture needle configured to collect whole blood from a donor;
a blood separator configured to separate whole blood into a plasma product and a second blood component comprising red blood cells, the plasma line configured to deliver the plasma product to a plasma product collection container; a blood separator having a coupled plasma output port;
a donor line fluidly coupled to the venipuncture needle and configured to introduce whole blood from a donor into the blood separator, wherein flow through the donor line is controlled by a first pump; donor line and
an anticoagulant line coupled to an anticoagulant source, the anticoagulant line configured to mix anticoagulant with whole blood from a donor, and wherein the flow through the anticoagulant line is the anticoagulant line controlled by a second pump;
a touch screen configured to receive input from an operator;
a controller programmed to control operation of the system, the controller comprising:
Obtain the donor's weight, height, and hematocrit value,
Determine the target volume of plasma product (TVPP) to be collected based on the donor's weight or based on the donor's weight and height and at a given donor anticoagulant ratio (ACR) and hematocrit (Hct). determining the percentage of anticoagulant in the target volume of plasma product to be collected (% _ACTVPP ) based on the target volume of pure plasma to be collected (TVP) based on at least the donor's weight; , where TVPP=TVP/(1-%AC _TVPP ),
controlling the system to perform a collection and return cycle for collecting whole blood from a donor;
adding an anticoagulant to whole blood at a predetermined ratio (ACR);
separating the anticoagulated whole blood into a plasma product and the second component, and returning the second component to the donor;
obtaining the current value of the donor's hematocrit (Hct);
controlling the system to recalculate a target volume of plasma product (TVPP) based on the current value of the donor's hematocrit (Hct);
controlling the system to perform subsequent collection and return cycles;
The system is then programmed to account for changes in donor hematocrit in calculating the new target volume of plasma product to be collected. 17. The system of claim 16, wherein the controller is further programmed to calculate a target volume (TVP) of pure plasma to be collected as a multiple of the donor's body weight. A system for collecting plasma, the system comprising:
a venipuncture needle configured to collect whole blood from a donor;
a blood separator configured to separate whole blood into a plasma product and a second blood component comprising red blood cells, the plasma line configured to deliver the plasma product to a plasma product collection container; the blood separator having a coupled plasma output port;
a donor line fluidly coupled to the venipuncture needle and configured to introduce whole blood from a donor to the blood separator, wherein flow through the donor line is controlled by a first pump; donor line and
an anticoagulant line coupled to an anticoagulant source, the anticoagulant line configured to mix anticoagulant with whole blood from a donor, and wherein the flow through the anticoagulant line is the anticoagulant line controlled by a second pump;
a touch screen configured to receive input from an operator;
a controller programmed to control operation of the system, the controller comprising:
Obtain the donor's weight, height, and hematocrit,
The target volume of plasma product collected (TVPP), the percentage of anticoagulant in the target volume of plasma product collected (% AC _TVPP ), the donor's total blood volume (TBV) based on the donor's weight and height, and the target volume of pure plasma (TVP) to be collected as a percentage of TBV, where TVPP=TVP/(1-% AC _TVPP ) and
controlling the system to perform a collection and return cycle for collecting whole blood from a donor;
adding an anticoagulant to whole blood at a predetermined ratio (ACR);
separating the anticoagulated whole blood into a plasma product and the second component, and returning the second component to the donor;
obtaining the current value of the donor's hematocrit (Hct);
controlling the system to recalculate a target volume of plasma product (TVPP) based on the current value of the donor's hematocrit (Hct);
controlling the system to perform subsequent collection and return cycles;
The system is then programmed to account for changes in donor hematocrit in calculating the new target volume of plasma product to be collected. The control unit further calculates the total blood volume (TBV) of the donor based on the donor's weight (Wt) and height (Ht) for calculating the donor's body mass index (BMI). 19. The system of claim 18, wherein the system is programmed to calculate /√(BMI/22), where BMI=Wt/Ht ² . ACR is the ratio of the volume of whole blood to the volume of anticoagulant (ACR=WB/AC), and the controller controls the percentage of anticoagulant in the target volume of plasma product (%AC _TVPP ): 19. The system of claim 16 or claim 18, configured to determine that %AC _TVPP = 1/(1+ACR(1-Hct)). ACR is the ratio of the sum of the volume of whole blood and the volume of anticoagulant to the volume of anticoagulant (ACR=(WB+AC)/AC), and the control unit controls the amount of anticoagulation in the target volume of plasma product. 19. The method of claim 16 or claim 18, wherein the method is configured to determine the percentage of the agent (%AC _TVPP ) such that %AC _TVPP = 1/(1+(ACR-1)(1-Hct)). The system described. The controller is further programmed to calculate the donor's total blood volume (TBV) based on the donor's weight (Wt), height (Ht) and gender (male or female); For women, TBV=(0.3669×Ht ³ )+(0.03219×Wt)+0.6041, and for women, TBV=(0.3561×Ht ³ )+(0.03308×Wt)+0. 19. The system of claim 18, wherein the Ht is in meters and the Wt is in kilograms. The controller is programmed to repeat the collection and return steps until a target volume of plasma product to be collected is collected, and the target volume of pure plasma to be collected is determined at each collection stage. 19. The system of claim 16 or claim 18, wherein the system is re-determined before the start of. the controller is programmed to initiate the final return of the second blood component when the volume of plasma product in the plasma collection container reaches a target volume of plasma product; A system according to claim 16 or claim 18. 17. or Claim 16, wherein the controller is programmed to electronically receive donor parameters from a donor management system and to determine a target volume of plasma product based at least in part on the donor parameters. 18. The system according to 18. The donor management system is programmed to calculate the target volume of plasma product, and the controller calculates the target volume of pure plasma by receiving the target volume of pure plasma from the donor management system. 26. The system of claim 25, wherein the system is programmed to determine volume. 19. The system of claim 16 or claim 18, wherein the controller is programmed to determine a target volume of plasma product prior to collecting whole blood from the donor. 19. The system of claim 16 or claim 18, wherein the controller is further programmed to take into account anticoagulant introduced into the plasma collection container separately from the plasma product.

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