CN116801926A - Systems and methods for plasma collection - Google Patents
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Abstract
A plasma withdrawal system and a method for operating a plasma withdrawal system are provided, by which the volume of plasma product (i.e. anticoagulated plasma) is such that the target volume of pure plasma in the plasma product is determined based on a donor-specific property. In particular, the target amount of pure plasma to be collected is based on the weight of the donor or the weight and height of the donor. The target volume TVP of pure plasma to be collected may be a multiple of the donor's weight. Alternatively, the TVP may be a multiple of the total blood volume TBV of the donor, where the TBV of the donor is determined based on the weight and height of the donor. A target volume TVPP of the plasma product to be collected is established and the separation of whole blood into a plasma component and a second component is continued until the volume of plasma product in the collection container is equal to TVPP.
Description
Cross Reference to Related Applications
The present application claims priority from US 17/306,099 submitted at 3 of 5.2021 and US 63/140,534 submitted at 22 of 2021 and relates to US 17/078,824 submitted at 23 of 10.2020, US 17/062,368 submitted at 2 of 10.2020, US 17/041,701 submitted at 25 of 9.2020, US 16/739,441 submitted at 10.1.2020, PCT/US2019/033318 submitted at 21 of 5.2019, US 62/846,400 submitted at 10 of 5.2019, US 62/752,480 submitted at 30 of 10.2018 and US 62/674,144 submitted at 21 of 5.5, each of which is incorporated herein by reference in its entirety.
Technical Field
The present application relates to systems and methods for performing plasma extraction (plasmapheresis), and more particularly to plasma extraction systems and methods in which the volume of pure plasma that can be collected from a particular donor is optimized.
Background
Plasma withdrawal is a apheresis procedure (apheresis procedure) in which whole blood is withdrawn from a donor, plasma is separated and retained from other cellular blood components (red blood cells, platelets, and white blood cells), and then the cellular blood components are returned to the donor. Separation of plasma from cellular components is typically accomplished in an automated process by centrifugation or membrane filtration.
In automatic plasma withdrawal, whole blood is drawn from a donor, mixed with an anticoagulant 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 determined by the weight scale associated with the plasma collection container, the withdrawal of whole blood from the donor is stopped, and red blood cells and other cellular components are returned to the donor. Typically, the plasma product is collected in multiple collection and re-infusion cycles until a total target volume of anticoagulated plasma has been collected. The anticoagulated plasma may be used in later blood transfusion or further production.
Plasma collected for use as source material for further production ("source plasma") is collected from multiple donors and combined or pooled for this purpose. The FDA issued guidelines for the registered blood collection center regarding the volume of plasma that can be collected as source plasma during plasma withdrawal in order to improve the consistency of the process for producing source plasma and minimize the chance of personnel error. (FDA regulations: "Volume limitation-automatic collection of source plasma (Volume Limits-Automated Collection of Source Plasma) (11/4/92)").
The FDA regulations set forth simplified plasma volume nomograms in which the volume (or weight) of pure (raw) plasma that can be collected from a particular donor is limited to ensure the safety and comfort of the donor. More specifically, the FDA nomogram limits the volume (or weight) of plasma based on the weight of the donor and establishes a volume of anticoagulant that can be added at a 1:16 ratio of anticoagulant to anticoagulant or at 0.06 parts anticoagulant to 1 part anticoagulant to reach a maximum collection volume for a particular donor that is the sum of the plasma plus anticoagulant.
The simplified nomogram given in the FDA regulations has been the primary method used by blood collection centers to determine the collection volume of plasma products. Thus, plasma withdrawal devices used in such centers are typically programmed to collect a specific volume/weight of anticoagulated plasma (assuming a known density) according to the maximum collection volume allowed by the FDA nomogram, wherein the anticoagulants are added to whole blood at a ratio of 1:16 or 0.06.
One simplification made in the FDA nomogram is to disregard the donor hematocrit in determining the target collection volume of the plasma product. However, the relative ratio of pure plasma to anticoagulant in the plasma product depends on the hematocrit of the donor and the ratio of anticoagulant to whole blood of the donor. As a result, a higher hematocrit donor reaches the maximum collection volume given in the FDA nomogram before reaching the maximum pure plasma volume that can be safely collected from the donor. This represents a low efficiency of the plasma collection center, since the volume of pure plasma collected is less than the maximum possible.
Furthermore, the amount of pure plasma that can be safely collected from a donor may depend on factors other than the weight and hematocrit of the donor that affect the total blood volume of the donor, such as the height of the donor.
Since 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, since even a small increase in volume collected from each individual donor, when added together, results in a meaningful increase in the total volume of pooled plasma. If the plasma withdrawal apparatus is better able to target a pure plasma volume, more plasma protein can be collected from each donor, thereby increasing the overall efficiency of the plasma collection center. Thus, by the present disclosure, systems and methods for optimizing the volume of plasma collected consistent with donor safety and comfort are provided.
Disclosure of Invention
In a first aspect of the present disclosure, there is provided a system for collecting plasma from a donor, wherein the system comprises: an intravenous puncture needle for drawing whole blood from a donor; a blood separator for separating whole blood into a plasma product and a second blood component comprising red blood cells; a donor line coupled to the venous puncture needle for introducing whole blood from a donor to the blood separator; a first pump for controlling flow through the donor line; an anticoagulant line coupled to the anticoagulant source, the anticoagulant line for combining an 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 controller programmed to control operation of the system. The controller is configured to determine a Target Volume (TVPP) of the plasma product to be collected based on the weight and the donor hematocrit of the donor, or based on the weight and the height of the donor and the donor hematocrit, control the system to operate the aspiration and return cycle to withdraw whole blood from the donor, add anticoagulant to the whole blood at a predetermined ratio (ACR), separate the anticoagulated whole blood into the plasma product and the second component and return the second component to the donor, and stop withdrawing whole blood from the donor and begin final return of the second blood component when the measured volume of the plasma product in the plasma collection container reaches the target volume of the plasma product.
In a second aspect, the controller is programmed to: i) Calculating a Target Volume (TVP) of pure plasma to be collected based on the weight of the donor; and ii) calculating the percentage of anticoagulant (%AC) in the target volume of plasma product to be collected based on the predetermined anticoagulant ratio ACR and the donor hematocrit TVPP ) Wherein tvpp=tvp/(1-%ac) TVPP )。
In a third aspect, the controller is programmed to calculate a Total Blood Volume (TBV) of the donor based on the weight and height of the donor, calculate a Target Volume (TVP) of pure plasma to be collected that is a percentage of the TBV, and calculate a percentage of anticoagulant (%ac) in the plasma product of the target volume to be collected based on a predetermined anticoagulant ratio (ACR) and the hematocrit of the donor TVPP ) Wherein tvpp=tvp/(1-%ac) TVPP )。
In a fourth aspect, the controller is programmed to calculate a Total Blood Volume (TBV) of the donor based on the weight and height of the donor to calculate a Body Mass Index (BMI) of the donor such that TBV = 70/(sqrtBMI/22) (Lemmens equation).
In a fifth aspect, the controller is programmed to be based on the weight (Wt), height (Ht) and weight (Wt) of the donorGender (male or female) to calculate Total Blood Volume (TBV) of the donor such that for male tbv= (0.3669×ht 3 ) ++ (0.03215×wt) +0.6041, and for females tbv= (0.3561×ht) 3 ) ++ (0.03308 x Wt) +0.1833, wherein Ht is in meters and Wt is in kilograms (Nadler formula).
In a sixth aspect, a method for performing plasma withdrawal to collect a volume of plasma product (i.e., anticoagulated plasma, VPP) consistent with the safety and comfort of a donor is provided such that a Target Volume (TVP) of pure plasma in the plasma product is determined based on the donor-specific characteristics. In particular, the target volume TVP of pure plasma to be collected is based on the weight of the donor, or the weight and height of the donor.
In a seventh aspect, the target volume TVP of pure plasma to be collected may be a multiple of the donor's weight. Alternatively, the TVP may be a multiple of the total blood volume TBV of the donor, where the TBV of the donor is determined based on the weight and height of the donor using accepted methods such as the Lemmens equation or the Nadler equation.
Target volume/weight based on pure plasma and% AC of anticoagulant AC in plasma product TVPP To establish a target volume TVPP of the plasma product to be collected such that TVPP = TVP/(1-%ac) TVPP ) wherein%AC TVPP Is based on the AC ratio ACR and the hematocrit of the donor.
Once the TVPP is determined, a plasma withdrawal process begins in which whole blood is drawn from a donor, mixed with an anticoagulant in a specific ratio, and then separated into plasma, red blood cells, and other cellular components. Once the TVPP has been collected, as determined by, for example, a weight scale associated with the plasma collection container, the withdrawal of whole blood 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 amount of plasma product to be collected, the hematocrit of the donor may be determined prior to the collection phase of each cycle by calculation or based on a signal from a sensor or the like indicative of the hematocrit of the donor. Furthermore, the amount of plasma product in the plasma collection container may be determined by, for example, a weight scale associated with the plasma collection container or a direct measurement volume optical sensor.
In other aspects, a method is provided for operating a plasma withdrawal system to collect a plasma product volume comprising a maximum allowable volume/weight of raw plasma according to the limits given in the FDA nomogram based on the weight of the donor.
In order to collect the maximum volume/weight of raw plasma allowed by the FDA nomogram, a modified nomogram is provided that uses the hematocrit of the donor to calculate the target volume/weight of a plasma product having the maximum volume of raw plasma allowed by the FDA nomogram. The calculated volume/weight of raw plasma is compared to the maximum volume/weight of raw plasma allowed by the FDA nomogram. If the calculated volume/weight of the raw plasma is less than the maximum allowable volume/weight, the volume/weight of the plasma product to be collected is up-regulated by the following amounts according to the maximum volume/weight allowed for the plasma product by the FDA nomogram: this amount is equal to the difference plus the additional amount of anticoagulant added to treat the additional volume/weight of plasma.
Thus, given the hematocrit of the donor and the AC ratio of the instrument, the volume of additional raw plasma that can be safely collected from the donor is determined, consistent with the constraints set forth in the FDA nomogram, and then the total volume/weight of the plasma product to be collected is adjusted accordingly based on the weight of the donor as set forth in the FDA nomogram.
Typically, the plasma withdrawal process includes a continuous cycle of alternating stages, one of which is drawing whole blood from the donor and separating and collecting plasma, and the other of which is returning the separated red blood cells and any other non-RBC cell components to the donor. The hematocrit of the donor will change during the plasma withdrawal process, affecting the amount of anticoagulant in the plasma product collected from one cycle to the next.
Thus, in a first aspect of the present disclosure, a new hematocrit value of the donor is determined prior to starting a subsequent extraction/separation phase, and the target volume/weight of plasma product for the process is recalculated prior to starting each extraction/separation phase to ensure that the maximum amount of raw plasma allowed by the FDA nomogram is collected.
In another aspect, another method for collecting a volume of plasma during a apheresis procedure is provided. The method comprises the following steps: determination of total Whole blood volume V of donor b The method comprises the steps of carrying out a first treatment on the surface of the Based on V b Determining the volume of raw plasma (V RP ) The method comprises the steps of carrying out a first treatment on the surface of the Determining a target volume (V) of the plasma product to be collected based on an anticoagulant ratio established for the process (ACR, defined as the ratio of the volume of donor blood to the volume of anticoagulant for donor blood without anticoagulant) and Hct of the donor PP ) Wherein V is PP Is equal to the volume (V RP ) Added to V during the singulation process RP Volume of anticoagulant (V) AC ) So that V PP ＝V RP * K, wherein k= (ACR (1-Hct/100) +1)/(ACR (1-Hct/100)); drawing whole blood from a donor; adding an anticoagulant to whole blood in an amount consistent with ACR; separating a plasma product from whole blood; and transferring the plasma product to the collection container until the volume of plasma product in the collection container reaches V PP Until that point. Since the plasma withdrawal process includes multiple withdrawal/separation and return phases, the V for the process is recalculated before each withdrawal/separation phase begins based on the value of the hematocrit of the donor determined before each withdrawal phase begins PP And adjusts the target volume of the plasma product accordingly. Alternatively, the calculated value based on the total plasma volume of the donor, which calculated value is based on V b And hematocrit of the donor-determining V RP 。
In another aspect, a method for determining the volume (V PP ) Wherein V is PP Is equal to the volume (V RP ) Added to V during the singulation process RP Is the anticoagulant body of (a)Product (V) AC ). The method comprises the following steps: determining the weight (W) kg ) And gender (M or F); determining a hematocrit (Hct) of the donor; based on the weight of the donor (W kg ) And sex (M or F) determination of the volume (V) of raw plasma that can be collected RP ) The method comprises the steps of carrying out a first treatment on the surface of the Determining V based on anticoagulant ratio (ACR) and Hct of donor PP And V is equal to RP The ratio K between such that k=v PP /V RP The method comprises the steps of carrying out a first treatment on the surface of the Determining V PP So that V PP ＝V RP * K. In addition, k= (ACR (1-Hct/100) +1)/(ACR (1-Hct/100)). In determining V PP Afterwards, whole blood is drawn from the donor; adding an anticoagulant to whole blood in an amount consistent with ACR; separating a plasma product from whole blood; and transferring the plasma product to a collection container. After the desired amount of whole blood has been drawn from the donor, the red blood cells are returned to the donor. Then, hct and V of the donor are determined before each pumping stage PP 。
In a related aspect, the aspirating step and the separating step are repeated until the volume of plasma product in the collection container reaches V PP Until that point.
In a related aspect, the hematocrit of the donor after the first acquisition phase may be calculated by volume balancing, assuming that the number of red blood cells of the donor is the same at the beginning of each aspiration cycle, while the total volume of blood decreases from one cycle to the next by an amount equal to the amount of raw plasma acquired. Alternatively, the hematocrit of the donor at the beginning of each pumping cycle may be measured by an optical or other sensor.
In another aspect, the volume of raw plasma that may be collected from a particular donor may be determined in any of several different ways. These include, for example: FDA nomogram, which only considers the weight of the donor; the modified FDA nomogram, which further takes into account the hematocrit of the donor, and takes into account the portion of the total blood volume or total plasma volume calculated for a particular donor. The total blood volume or total plasma volume may be determined, for example, using: nadler equation; gilcher five-way method; a form provided by the international hematoma standardization association (ICSH); or any other generally accepted method of conforming to the safety and comfort of the donor using the height, weight, sex and age of the donor.
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 set further comprises: i) A separator for separating whole blood into a plasma portion and a concentrated cell portion, the separator having an input with a blood line integrally connected to the input for transferring whole blood from the donor to the separator, a plasma output port integrally connected through the plasma line to a plasma collection container, and a concentrated cell outlet port integrally connected to a reservoir for receiving concentrated cells prior to reinfusion to the donor; ii) a donor line terminating in a venous puncture needle for transferring whole blood from the donor to the blood line; iii) An anticoagulant line integrally connected to the blood line and configured to be connected to an anticoagulant source, the anticoagulant line for delivering anticoagulant to the donor line; and iv) a re-infusion line for transferring concentrated cells from the reservoir to the donor line.
The reusable hardware components further include: i) A peristaltic first pump for delivering anticoagulant into the blood line at a controlled rate during the collection phase; ii) a second pump for delivering anticoagulated whole blood to the separator during the collection phase and returning concentrated cellular components during the reinfusion phase; iii) A third pump for delivering the concentrated cellular component from the separator to the reservoir during the harvesting phase; iv) a clamp associated with each of the blood line, the plasma line, and the re-infusion line; v) a weight scale for weighing each of the plasma collection container, reservoir, and the anticoagulant source; and vi) a programmable controller including a touch screen for receiving input from an operator, the programmable controller configured to receive signals from each of the weight scales and automatically operate the first, second and third pumps and clamps to separate whole blood into a plasma portion and a concentrated cell portion during the harvest phase and to return the concentrated cells to the donor during the reinfusion phase. The programmable controller is further configured to determine a target amount of plasma product to be collected in the plasma collection container according to any of the methods described herein, and the programmable controller is configured to terminate the collection phase upon receiving a signal that the amount of plasma product in the plasma collection container is equal to the target amount of plasma product determined by the controller. In determining the target amount of plasma product to be collected, the controller may be configured to calculate the hematocrit of the donor prior to the collection phase of each cycle. Alternatively or additionally, the controller may receive a signal from a sensor or the like indicative of the hematocrit of the donor. Furthermore, the amount of plasma product in the plasma collection container may be determined by, for example, a weight scale associated with the plasma collection container or an optical sensor that directly measures volume.
Drawings
Fig. 1 is a perspective view of an exemplary plasma withdrawal apparatus suitable for use in 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 with the plasma withdrawal system of fig. 1, with portions broken away to show details.
Fig. 3 is a perspective view of the front panel of the plasma withdrawal system of fig. 1 showing the components of the disposable set mounted to the front panel.
Fig. 4 is a schematic diagram showing the operation of the plasma withdrawal system in the collection phase.
Fig. 5 is a schematic diagram showing the operation of the plasma withdrawal system during the re-infusion phase.
Fig. 6a and 6b are flowcharts showing the method steps for collecting a target volume of pure plasma in the present application.
Fig. 7 is a table showing the volume of purified plasma based on donor hematocrit contained within the plasma product volume limits set by the FDA nomogram using a ratio of anticoagulant to whole blood of 1:16.
Fig. 8 is a table showing the "unclassified" volume of pure plasma in a plasma product based on the difference between the values listed in fig. 7 and the maximum volume of pure plasma that can be collected based on FDA nomogram.
Fig. 9 is a table showing the volumes of plasma product that can be collected from a donor based on the weight of the donor and hematocrit that would result in the maximum allowable volume of pure plasma allowed by the FDA nomogram.
Figure 10 is a table showing inputs to a programmable controller for performing a hypothetical plasma withdrawal process according to the method of the present application.
Fig. 11a, 11b include a table divided into two sections, which illustrate how the hematocrit of a donor increases during a hypothetical plasma withdrawal based on the input in the table of fig. 10, and results in an increase in the total collection volume of plasma product necessary to collect a target volume of pure plasma.
Fig. 12 is a graph illustrating the dilution of IgG during plasma removal.
Detailed Description
A more detailed description of systems and methods according to the present disclosure will be set forth below. It should be understood that the following description of specific apparatus and methods is intended to be exemplary, rather than exhaustive of all possible variations or applications. Accordingly, the scope of the present disclosure is not intended to be limiting and should be understood to encompass modifications or embodiments that would occur to one of ordinary skill. Various aspects of the systems and methods are described in more detail in US 2020/0147289, which is incorporated herein by reference.
In the context of the present application, plasma withdrawal is performed on an automated system comprising a hardware component generally indicated at 10 and a disposable set generally indicated at 12 to collect plasma to be treated as source plasma. Referring to fig. 1-5 and as described in more detail below, the disposable set 12 includes an integrally connected separator, a container, and tubing to transport blood and solutions within a sterile fluid path.
The separator 14, best seen in fig. 2, has a rotating membrane filter 16, the rotating membrane filter 16 being mounted to a rotor 18 for rotation within a housing 20 to separate blood into components. A detailed description of a rotating membrane separator can be found in U.S. patent No.5,194,145 to Schoendorfer, which is incorporated herein by reference. As can be appreciated, in different systems, separation of whole blood can be accomplished by centrifugation. See, for example, US 5,360,542 to Williamson et al.
During plasma withdrawal, anticoagulated whole blood enters separator 14 through whole blood input port 22. Plasma is separated by the rotating membrane filter and then flows out of the plasma output port 24, through the plasma line 26, and into the plasma collection container 28. Concentrated cells are pumped from the concentrated cell output port 30 into the reservoir 32, with the cells remaining in the reservoir 32 until reinfusion to the donor.
The disposable set 12 further includes the following tubing lines: a line for introducing whole blood from a donor into the system during collection and returning concentrated cells to the donor during reinfusion (donor line 34, which donor line 34 terminates in a venous puncture needle 36), and a line for delivering anticoagulated whole blood to a separator (blood line 38), a line for delivering concentrated cells to a reservoir (cell line 40), a line for delivering concentrated cells from a reservoir to a donor line (reinfusion line 42), a line for delivering plasma to a plasma collection container (plasma line 44), a line for normal saline (normal saline water line 46), and a line for anticoagulants (AC line 48).
The hardware component 10 includes a programmable controller 50 and a touch screen 52 having a graphical user interface ("GUI") by which an operator controls the plasmapheresis process. For example, the GUI allows entry of any of the following: donor ID, donor gender, donor height, donor weight, donor age, donor hematocrit/hemoglobin; target saline infusion volume (if saline regimen is selected) and target plasma volume. The touch screen 52 also enables an operator to collect status information and handle error conditions.
Three peristaltic pumps are positioned on the front panel of the hardware component 10, including an AC pump 54, a blood pump 56, and a cell pump 58. As whole blood enters the kit from the donor, the AC pump 54 delivers an anticoagulant solution (AC) into the blood line 38 at a controlled rate. The blood pump 56 delivers anticoagulated whole blood to the separator during the collection phase of the plasma withdrawal process and returns concentrated cellular components to the donor and replacement fluid to the donor if needed during the re-infusion phase of the plasma withdrawal process. The cell pump 58 delivers the concentrated cellular components from the separator 14 to a reservoir during the harvesting phase.
The front panel also includes four clamps into which tubing of the disposable set 12 fits, including a re-infusion clamp 60, a blood clamp 62, a saline clamp 64, and a plasma clamp 66. The reinfusion fixture 60 is closed to block the reinfusion line (42) during the harvest phase (fig. 5) and is open during the reinfusion phase (fig. 5) to allow the blood pump to reinfuse the concentrated cellular component from the reservoir 32 to the donor. The blood clamp 62 is opened during the collection phase to allow anticoagulated whole blood to be pumped to the separator 14 and closed during the reinfusion phase to block the blood line 38. The saline clamp 64 is closed to block the saline line 46 during the harvesting phase and during the re-infusion of the separated cellular components. If saline is used as the replacement fluid, the saline clamp 64 is opened during the re-infusion phase. The plasma clamp 66 is opened during the collection phase to allow plasma to flow into the plasma collection container 28 and closed during the re-infusion phase.
Hardware component 10 includes three weight scales to monitor the current plasma collection volume (scale 68), AC solution volume (scale 70), and concentrated cell component volume (scale 72). 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 process. As illustrated, the disposable set 12 includes a single intravenous needle 36 through which the intravenous needle 36 draws whole blood from the donor during the collection phase (fig. 4) and through which the concentrated cells are returned to the donor during the reinfusion phase (fig. 5). As mentioned above, the plasma withdrawal process may include a plurality of cycles, each cycle having an acquisition/separation phase followed by a return or re-infusion phase. 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. During the reinfusion phase, concentrated cells from reservoir 32 are reinfused to the donor through intravenous needle 36. Plasma withdrawal using a single intravenous puncture needle 36 may involve multiple collection and re-infusion cycles.
Returning to fig. 4, during the harvesting phase, the anticoagulation solution (AC) is pumped at a controlled rate and mixed with whole blood as it enters the disposable set 12. The anticoagulated blood is pumped to separator 14, where plasma is separated from cellular components in separator 14 and directed to plasma collection container 28.
From separator 14, the cellular components are pumped to reservoir 32. The collection phase stops when the reservoir 32 reaches the desired volume of concentrated cells or if the target plasma collection volume has been reached.
Then, the reinfusion phase begins. Referring to fig. 5, during the re-infusion phase, the blood pump 56 reverses direction and pumps the concentrated cells from the reservoir 32 back to the donor through the single needle 36. If a saline regimen is selected, according to which saline is returned to the donor as a replacement fluid for the collected plasma, saline infusion is performed after the final re-infusion phase.
The automated plasma collection apparatus is configured to collect a volume/weight of anticoagulated plasma (i.e., plasma product) having a maximum volume/weight of raw plasma allowed by the donor under the constraints set forth in the FDA nomogram. To maximize the volume of raw plasma containing plasma product, the device is programmed with a nomogram that takes into account the hematocrit of the donor. Given the hematocrit of the donor and the AC ratio of the instrument, the total volume/weight of the plasma product to be collected may be determined such that the plasma product includes a maximum volume/weight of plasma raw material fraction that may be collected from the donor consistent with the total volume/weight limits given in the FDA nomogram for raw plasma. By programming the calculation into the controller, the likelihood of operator error is reduced as compared to calculating the acquisition volume off-line and then inputting the acquisition volume into the instrument.
During plasma withdrawal, when the anticoagulant is mixed with whole blood while whole blood is drawn from the donor, the anticoagulant is uniformly distributed in the pure/raw plasma in the blood. However, the amount of pure/raw plasma in whole blood depends on the hematocrit Hct of the whole blood. The following relationship is established:
volume of RBC = volume of whole blood Hct/100. [1]
Pure plasma/raw plasma volume = whole blood volume (1-Hct/100). [2]
When the anticoagulant is mixed with whole blood, the anticoagulant can be metered at an AC ratio ACR of 16 parts whole blood to 1 part AC or 1 part whole blood to 0.06 parts AC.
ACR = volume of whole blood/volume of anticoagulant (donor blood without anticoagulant). [3]
( This produced slightly different results from the FDA nomogram, which, as mentioned above, normalizes the volume of anticoagulant that can be added to: the ratio of anticoagulant to anticoagulated blood is 1:16, or 0.06 parts anticoagulant to 1 part anticoagulated blood. )
Volume of anticoagulated blood = volume of anticoagulant + volume of whole blood. [4]
The following equation is combined:
volume of pure plasma/raw plasma = ACR x volume of anticoagulant (1-Hct/100). [5]
Since erythrocytes are returned to the donor:
volume of collected plasma product = volume of pure plasma/raw plasma + volume of anticoagulant. [6]
Equation [5] and equation [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]
Furthermore:
volume of collected plasma product = volume of pure plasma/raw plasma K, where k= (ACR (1-Hct/100) +1)/(ACR (1-Hct/100)). [8]
Taking into account the relationship expressed in the above equation, the volume of pure plasma/raw plasma contained within the allowed volume of plasma product under the FDA nomogram can be determined based on the hematocrit of the donor. The results of this calculation are given in fig. 7, fig. 7 showing the volume of pure plasma/raw plasma contained within the plasma product volume limit set by the FDA nomogram based on the hematocrit of the donor.
As can be appreciated with reference to fig. 7, for a donor weighing from 110 pounds to 149 pounds (690 mL for such a donor, the maximum plasma product volume according to the FDA nomogram), if the donor has a hematocrit of 42 or greater, the volume of raw plasma collected is less than 625mL allowed by the FDA nomogram. For a donor having a weight of 150 lbs to 174 lbs (825 mL for such a donor according to the FDA nomogram) and for a donor having a weight of 175 lbs or more (880 mL for such a donor according to the FDA nomogram), the situation is similar when the hematocrit of the donor is 40 or greater.
The table given in fig. 8 presents the "undesired" raw plasma volume in the plasma product based on the difference between the values given in fig. 7 and the maximum volume of pure plasma/raw plasma that can be collected based on the FDA nomogram. Thus, as shown in the table set forth in fig. 9, the plasma product collected from any particular donor can be adjusted according to the plasma product set forth in the FDA nomogram in the following amounts: this amount corresponds to the amount of "undesired" pure plasma/raw plasma given in fig. 8 plus the amount of anticoagulant needed to treat the additional volume.
Alternatively, the volume of plasma product to be collected may be calculated by: first, determining the weight and hematocrit (Hct) of the donor; based on the weight of the donor (W kg ) Determination of the raw plasma (V) RP ) Is defined by the volume of (2); v was determined based on anticoagulant ratio (ACR; 1:16 or 0.06:1 according to FDA Noemal diagram) and Hct of the donor PP And V is equal to RP The ratio K between such that k=v PP /V RP The method comprises the steps of carrying out a first treatment on the surface of the Determining V PP So that V PP ＝V RP * K. In addition, k= (ACR (1-Hct/100) +1)/(ACR (1-Hct/100)).
In a further alternative, the volume (V PP ): first, the weight (W) kg ) And hematocrit (Hct); based on the weight of the donor (W kg ) Determination of the raw plasma (V) RP ) Is defined by the volume of (2); the volume of anticoagulant to be added (V) is determined based on the anticoagulant ratio (ACR; 1:16 or 0.06:1 according to FDA Noemal diagram) and the hematocrit of the donor (ACR) AC ) So that V AC ＝V RP * (ACR (1-Hct/100)); and determining the acquisition volume such that V PP ＝V RP +V AC 。
According to one aspect of the present disclosure, an automated plasma collection device is configured to collect a volume/weight of a plasma product (pure plasma + anticoagulant) having a pure plasma volume/weight allowed by a donor as determined by either of two methods set forth in more detail below.
Referring to fig. 6a, a first method (70) for collecting a plasma product of a target volume TVPP is illustrated. In this method, the Target Volume (TVPP) of the plasma product is determined by: the Target Volume (TVP) of the pure plasma to be collected is first calculated based on the weight of the donor (step 72), and then the percentage of anticoagulant (%ac) in the plasma product of the target volume to be collected is determined based on the predetermined anticoagulant ratio (ACR) and the hematocrit of the donor TVPP ) Wherein tvpp=tvp/(1-%ac) TVPP ) (step 74). In this method, no intervening calculations of the total blood volume or total plasma volume of the donor are required prior to determining the target collection volume of the donor's plasma, although such calculations may be included in alternative embodiments.
Various methods may be used for determining a target volume of pure plasma that may be directly collected based on the weight of the donor. For example, the weight of the donor may be multiplied by the establishmentConstant "K" of (2) 1 "(e.g., 10 mL/kg). Alternatively, the weight of the donor may be divided into weight categories or ranges (e.g., at least three categories, at least six categories, etc.), with a fixed volume established for each category (in the FDA nomogram, as discussed above, the range of donor weights is divided into three categories).
The anticoagulant ratio ACR can be defined in one of two different ways. In the first mode, ACR is the ratio of whole blood volume to anticoagulant volume (acr=wb/AC). In a second approach, ACR is the whole blood volume plus the ratio of anticoagulant volume to anticoagulant volume (acr= (wb+ac)/AC). Percentage% AC of anticoagulant in the target volume of plasma product if acr=wb/AC TVPP The determination is made according to the following equation: % AC TVPP =1/(1+acr (1-Hct)), where ACR and Hct are expressed as percentages. If acr= (wb+ac)/AC), then the percentage of anticoagulant in the target volume of plasma product%ac TVPP The determination is made according to the following equation: % AC TVPP =1/(1+ (ACR-1) (1-Hct)). ACR can be expressed as a ratio or percentage, and can vary from 7:1 to 20:1, or from about 5% to 14%. Exemplary ACRs are 16:1 or 6.25%.
Returning to fig. 6a, once the TVPP has been determined, whole blood is drawn from the donor (step 76), as described above, and combined 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) cells (step 80). The plasma product (pure plasma and anticoagulant) is collected in the plasma collection container 28 (step 82), while the separated red blood cells are collected in the reservoir 32. Upon collection of the plasma product, the volume VPP of the plasma product (pure plasma and anticoagulant) in the plasma container is determined (step 84). When VPP is equal to the Target Volume of Plasma Product (TVPP), whole blood withdrawal is stopped and any 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 plasma product of a target volume TVPP is illustrated. In the method, a target volume TPPV of the plasma product is determined by: head partThe Total Blood Volume (TBV) of the donor is first calculated based on the weight and height of the donor (step 92), the target volume TVP of pure plasma to be collected, which is a percentage of the TBV, is calculated (step 94), and the percentage of anticoagulant (% AC) in the plasma product of the target volume to be collected is calculated based on the predetermined anticoagulant ratio (ACR) and the hematocrit of the donor TVPP ) (step 96), and calculating TVPP, wherein TVPP = TVP/(1-%ac) TVPP ) (step 98). The% AC may be determined as described above in connection with the first method TVPP . In this method, there is no need to calculate the total plasma volume of the donor to determine the target collection volume of the donor's plasma.
The plasma volume of the donor may be estimated based on the total blood volume of the donor, and a volume of plasma consistent with the safety and comfort of the donor may be obtained based on the estimation. Methods that utilize donor parameters are typically used to estimate the total blood volume of the donor. The total blood volume of the donor may be determined using one or more of the following: the Lemmens equation (which uses the body mass index of the donor to determine total blood volume), the Nadler equation (which considers the height, sex, and weight of the donor), the Gilcher's five-way method (which considers sex, weight, and body shape (obese, emaciated, normal, or healthy)), or the standard set forth in the international blood standardization council ("ICSH") in br.j.haem.1995,89:748-56 (which considers the height, weight, age, and sex of the donor). Any other method may also be used to determine the total blood volume of the donor. In another embodiment, a plurality of such methods may be used, and the mean, average or weighted average of these methods is taken as the total blood volume of the donor. For example, once the total blood volume of the donor is determined, the total blood volume may be multiplied by a constant "K 2 "to estimate the plasma volume of the donor, wherein" K 2 "equal to (1-Hct of donor).
From analysis of demographic, screening and experimental data in 2015 to 2016 National Health and Nutrition Examination Survey (national health and nutrition survey), where gender, age, height, weight, pregnancy data and hematocrit were extracted and presented in British j.haemaology (British journal), 89:748-756 (1995) in Interpretation of measured red cell mass and plasma volume in adults: expert Panel on Radionuclides of the International Council for Standardization in Haematology (interpretation of measured erythrocyte mass and plasma volume in adults: international standardization of blood will radionuclide specialist group) by Pearson et al (based on analysis to arrive at the formula of the ICSH recommendation), it has been determined that up to 36% of available plasma can be collected while complying with current regulations for donors with certain characteristics (i.e., low weight women with high hematocrit). Plasma withdrawal procedures for such donors have been routinely performed without adverse effects and are therefore considered safe. This indicates that up to 36% of the available plasma from the donor can be safely collected during plasma withdrawal.
Considering that only negative deviations of the actual blood volume of the donor from the predicted/calculated total blood volume would present a potential risk, it may be appropriate to further down-regulate the available volume of plasma. Based on consideration of the deviation between calculated blood volumes as determined by Pearson et al, cited above.
Thus, the Total Blood Volume (TBV) of the donor may be calculated based on the weight (Wt) and height (Ht) of the donor to calculate the Body Mass Index (BMI) of the donor such that tbv=70/sqrt (BMI/22), where bmi=wt/Ht 2 And wherein Ht is in meters and Wt is in kilograms (Lemmens equation). See Lemmens et al, "Obenity Surgery", 16,2006, pages 773-776 "Estimating Blood Volume in Obese and Morbidly Obese Patients (blood volume of obese and morbid obese patients)”。
Alternatively, the Total Blood Volume (TBV) of the donor may be calculated based on the weight (Wt), height (Ht) and sex (male or female) of the donor such that for male, tbv= (0.3669×ht 3 ) ++ (0.03215×wt) +0.6041, whereas for females tbv= (0.3561×ht) 3 ) ++ (0.03308 Wt) +0.1833, wherein Ht is in meters andwt is in kilograms (Nadler formula).
The percentage of TBV multiplied to obtain TVP (and ultimately TVPP) is selected to maximize the volume of pure plasma collected from the donor, consistent with the comfort and safety of the donor. In various embodiments, the percentage range may vary between about 1% and 15% of the TBV, at least 15%, less than 18%, between about 15% and 17%, about 12%, about 16% or about 18%. TVPP may also depend on the maximum volume to be acquired, e.g. 1000mL or 1050mL, irrespective of the TBV of the donor.
Based on Retzloff et al, J.Haemaology (journal of British blood science) 33,5:649-667 (1969)Erythrocyte Volume,Plasma Volume,and Lean Body Mass in Adult Men and Women (red blood cell volume, plasma volume and lean mass of adult men and Women)Regression analysis of experimental blood volume data presented in (1-Hct) the calculated volume TBV of whole blood can be adjusted so that tvp=0.36 (TBV-V) C ) Wherein V is C =523 mL. There is 95% confidence that: the predicted blood volumes of the individuals will differ by no more than 20.5%. Thus, the above-described 36% of the total plasma volume of the donor can be determined using a scale factor of 0.795, such that 28.6% of the calculated volume of the donor's raw plasma can be obtained consistent with the safety and comfort of the donor.
Returning to fig. 6b, once the TVPP has been determined as described above (based on TBV), whole blood is drawn from the donor (step 100) and combined with the anticoagulant based on a predetermined ratio (step 102). The anticoagulated whole blood is then introduced into separator 14, where it is separated into plasma and concentrated cells (erythrocytes) in separator 14 (step 104). The plasma product (pure plasma and anticoagulant) is collected in the plasma collection container 28 (step 106), while the separated red blood cells are collected in the reservoir 32. When the plasma product is collected, the volume VPP of the plasma product (pure plasma and anticoagulant) in the plasma container is determined (step 108). When VPP is equal to the Target Volume of Plasma Product (TVPP), whole blood withdrawal is stopped and any remaining blood components, such as red blood cells, are returned to the donor (step 110).
Thus, the collection volume (volume of plasma product) is determined based on the volume of raw plasma that can be collected from a particular donor, the hematocrit of the donor, and a fixed anticoagulant ratio (ACR). Thus, the method allows for more consistent control of the donor's raw plasma volume as the most relevant variable to the donor's safety.
In an exemplary method, an operator inputs an acquisition volume of a particular donor's plasma product into a system controller based on a target volume of raw plasma that may be acquired. The target plasma collection volume may be based on the weight and hematocrit of the donor during the initial collection phase, as illustrated in fig. 9, or by any of the other methods described above. Alternatively, the controller is configured to calculate the target plasma product collection volume for the initial collection phase according to methods such as those described above when the operator inputs, for example, the weight and hematocrit of the donor and/or any additional donor specific information required for the method for determining the total blood volume, total plasma volume, and target volume of available plasma that can be collected, such as the sex, height, and age of the donor.
In practice, the operator inputs into the system controller an acquisition volume of plasma product for a particular donor based on a target volume of raw plasma that can be acquired. The target plasma collection volume may be set forth in fig. 9 based on the weight of the donor and the hematocrit of the initial collection phase or by any of the other methods set forth above. Alternatively, the controller is configured to: for the initial collection phase, when the operator inputs, for example, the weight and hematocrit of the donor and/or any additional donor-specific information (e.g., the sex, height, and age of the donor) required by the method used to determine the total blood volume, total plasma volume, and target volume of available plasma that can be collected, the target plasma product collection volume is calculated according to methods such as those described above.
Preferably, the system administrator will initially set the following indications: that is, the target collection volume TVPP of the plasma product will be determined by the system (e.g., according to one of the methods described above) or directly entered into the system by the operator. If the operator were to enter TVPP, the system administrator would disable the ability of the controller to calculate TVPP. The system administrator will also set the AC ratio for all processes. If the controller were to determine TVPs, the administrator would set up the system to allow the appropriate donor-specific characteristics for calculating TVPs according to any of the methods described above to be entered into the controller by the operator or the donor management system, and the donor parameters (such as weight, height, and hematocrit) for qualification screening could be electronically sent to the instrument through the donor management system to avoid operator error in entering the donor parameters. The donor management system may also use the donor screening measurements and the relationship between the pure plasma volume and the collection volume to automatically calculate TVPP that is to be transmitted to the controller of the plasma withdrawal apparatus. Otherwise, the controller will calculate TVPP before starting to collect whole blood from the donor. Furthermore, if the controller/donor management system were to calculate TVPP, the administrator would set the system to enable the operator to input TVPP in addition to the calculated volume. Furthermore, if it is desired to shorten the estimated time for running/completing the process, for example, for reasons of comfort or convenience of the donor, the system will allow the operator to change the TVPP according to the calculated TVPP before or during the process. At the completion of this process, the actual volume of collected plasma product VPP and target volume TVPP, as well as the actual volume of collected pure plasma and target volume of plasma TPV will be displayed.
As mentioned above, the plasmapheresis procedure may be performed with multiple cycles of the collection/aspiration phase and the return/reinfusion phase. If the return/reinfusion phase does not include reinfusion of the surrogate fluid, the hematocrit of the donor will increase from one cycle to the next. Thus, if the target volume of the plasma product is determined based solely on the initial hematocrit of the donor without regard to the increase in hematocrit of the donor, the percentage of anticoagulant in the plasma product will be greater than would be predicted by the preliminary calculation used to determine the target volume of the plasma product (while the volume of pure plasma will be less). Thus, to ensure that the volume of plasma product collected contains the maximum volume of raw plasma that has been determined to be obtained from a particular donor, the target volume of plasma product is recalculated periodically throughout the plasma withdrawal process, such as before the beginning of the collection phase of each cycle, to account for variations in the hematocrit of the donor.
Thus, after a target volume of plasma product is determined based on the initial hematocrit of the donor, the plasma withdrawal process begins from the first pumping stage until a specified volume of whole blood (e.g., about 500 mL) has been drawn from the donor. Anticoagulants are added to 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 aspiration phase, red blood cells and non-RBC blood components are returned to the donor. The current volume of plasma product collected after the first pumping phase is determined, for example, by a weight scale. Then, a current value of the hematocrit of the donor is established and a new target volume of plasma product to be collected is determined, and a second cycle of the withdrawal phase and the return phase is performed. The cycle of the pumping and return phases is repeated until a target volume of plasma product is collected for the plasma withdrawal process, as recalculated before the beginning of each pumping phase. After the last harvesting phase, the controller initiates the last red blood cell re-infusion phase, after which the donor is disconnected.
Referring to the tables of fig. 10 and 11a, 11b, the benefits of performing a plasma withdrawal procedure with multiple acquisition/re-infusion cycles according to the methods given above can be seen. Figure 10 shows input data for a hypothetical plasma withdrawal process performed on a donor weighing 190 pounds (86.4 kg) and having an initial hematocrit of 44. Referring to the table of fig. 1, the simplified FDA nomogram limits the volume of plasma to be collected from such donors to 800mL and limits the total collection volume of plasma product to 880mL. In this example, the FDA nomogram limits the volume of raw plasma that can be collected for illustrative purposes only. As set forth above, other methods may be used to determine the amount of raw plasma that may be safely drawn from a donor, as opposed to the amount indicated by the FDA nomogram.
The number of collection and re-infusion cycles during plasma withdrawal may range from three to twelve. In the hypothetical plasma withdrawal process, there are five collection and reinfusion cycles, which are chosen for illustrative purposes.
Before the first collection cycle begins, 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 initial hematocrit of the donor. As given in the first row of the table (beginning of cycle 1), the initial target volume of plasma product to be collected is 889mL, which is the same as indicated by the table of fig. 9 for a donor weighing 175 pounds or more and having a hematocrit of 44, in order to obtain FDA-limited 800mL of raw plasma from the donor.
During each collection phase, 500mL of whole blood is aspirated from the donor, and anticoagulant is added to the whole blood at a predetermined ratio (i.e., 1:16) such that 31mL is added for each collection cycle of 500 mL. Whole blood plus anticoagulant is separated into a plasma fraction and a red blood cell fraction.
During the first return phase (end of cycle 1 return), the red blood cells and "non-RBC" blood components are returned to the donor such that the hematocrit of the donor increases to 45.6% at the end of the first return cycle, calculated by the controller based on the fact: the blood volume is reduced by the amount of raw plasma collected, while the number of red blood cells in the total blood volume remains the same as at the beginning of the plasma withdrawal process. The controller may also consider the volume of anticoagulant reinfused with the red blood cells at each return phase and the residual anticoagulant in the donor whole blood aspirated at cycle 2 and thereafter when determining a new hematocrit value for the next cycle. The total target volume of raw plasma and plasma product to be collected for the process is then recalculated based on the raw plasma volume of the donor and the new increased hematocrit. This provided a new target acquisition volume of 891mL.
The second acquisition phase was then performed, resulting in a total of 430mL of plasma product comprising 386mL of raw plasma being acquired in the first two acquisition phases (end of cycle 2 aspiration). The red blood cells and "non-RBC" blood components are returned again to the donor, after which the hematocrit of the donor is calculated to be 47.2%.
Two more 500mL acquisition phases are performed, each phase being followed by a return phase, wherein a new value for the volume of raw plasma to be acquired and the total volume of plasma product is determined before each acquisition phase starts. As the hematocrit of the donor increased, the target acquisition volume recalculated for the procedure increased to 893mL (for the third acquisition phase) and then to 894mL (for the fourth acquisition phase). A fifth "micro" collection cycle was performed to bring the volume of raw plasma collected to 800mL allowed by the FDA nomogram for the hypothetical donor. The recalculated target collection volume for the plasma product of the fifth collection phase was maintained at 894mL.
Thus, as shown in the above example, when the target collection volume for the plasma product is recalculated for each collection phase, a target collection volume for the plasma product of 894mL is obtained, which is required in order to collect a target volume of 800mL of raw plasma. In contrast, if the target collection volume is determined based solely on the initial hematocrit of the donor, 889mL of plasma product will be collected; alternatively, 880mL of plasma product will be collected if the target collection volume is based on a simplified FDA nomogram. In both cases, a target volume of less than 800mL will be acquired.
The higher the accuracy of the hematocrit of the donor that can be determined before and during the procedure, the more likely the target volume of collected plasma product will include the maximum volume of raw plasma that can be collected for a particular donor. As described above, the hematocrit of the donor during the procedure is based on the following assumptions: 100% of the red blood cells extracted in each aspiration cycle are reinfused in each return cycle with 100% non-RBC cell product and a volume of anticoagulant. However, it has been determined that during the blood separation process, interstitial fluidWill migrate to the intravascular space and thereby restore half of the extraction volume. See Saito et al, transfusions 2013;53 (11) 2744-50Interstitial fluid shifts to plasma compartment during blood Donation (in donation of blood) Interstitial fluid transferred to the plasma chamber during the transfer period. At each return stage, the transferred interstitial fluid is reinfused in addition to red blood cells, non-RBC cell products and anticoagulants. Thus, considering that transfer of interstitial fluid will result in a more accurate determination of hematocrit, and thus a more accurate determination of the target volume of plasma product, this will yield the maximum amount of raw plasma.
Transfer of interstitial fluid during plasma withdrawal has been demonstrated by tracking the levels of immunoglobulin G (IgG) of the donor during plasma withdrawal. See, for example, burkhardt et al, transfusions 2017;56:417-420Immunoglobulin G levels during collection of large volume plasma for fraction (immunoglobulin G level during collection of large volumes of plasma for isolation). Without transfer of interstitial fluid, the IgG levels of the donor will remain stable during plasma removal. 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 that has been transferred to the blood system.
Referring to fig. 12, a plot of the volume of collected plasma (along the X-axis) versus IgG concentration (along the Y-axis) formed from the experiment is shown. It can be seen that from baseline of zero collected plasma (at the beginning of the procedure) to 200mL of collected plasma, the IgG of the donor was reduced by 9%, and from 200mL of collected plasma to 800mL of collected plasma, the IgG of the donor was reduced by another 4%. This can be attributed to: interstitial fluid transfer is equivalent to about 9% of the initial total blood volume of the donor (after 200mL of plasma is collected) to about 13% of the initial total blood volume of the donor (after 800mL of plasma is collected).
The following relationship between the amount of IgG concentration of the donor and the volume of plasma collected has been established: y= 1.0017x -0.02 Where y=igg concentration, and x=the collected plasma volume. Thus, transfer of the blood volume of the donor through the interstitial fluidThe ratio of the shift substitution is equal to V b (1-y) wherein V b Is the initial volume of whole blood of the donor. Thus, the transfer volume of interstitial fluid can be calculated based on the volume of collected plasma, and this amount can be added to the volume of reinfused red blood cells, non-RBC cell products, and anticoagulant in each return phase to determine the current total blood volume of the donor and thus the hematocrit. As can be appreciated, the controller can be configured to automatically determine the volume of interstitial fluid that has been transferred based on the volume of the collected plasma and include the transferred volume in determining the hematocrit of the donor prior to each aspiration phase.
Alternatively, other methods of directly measuring the hematocrit of the donor may be employed such as an optical sensor, or, if a centrifugal separator is used, the volume of red blood cells in the centrifuge.
In addition, the anticoagulant may be introduced into the disposable set in a pre-treatment step prior to the initiation of the plasma withdrawal process, such as for priming the disposable set, thereby performing one or more pre-cycles or for performing other pre-process steps. As far as anticoagulants used for these purposes are ultimately to be directed directly to the plasma product collection container, anticoagulants used for these purposes may be considered in determining the volume contained in the plasma collection container that results in the target volume of collected raw plasma. For example, this may be accomplished by measuring the weight of the "filled" anticoagulant container and the weight of the anticoagulant container before the first pumping cycle begins and adding the volume of anticoagulant to the target volume of plasma product. The controller may be configured to automatically perform the steps necessary to account for anticoagulants introduced into the plasma collection container separately from anticoagulated plasma.
The method and system set forth above have several aspects. In a first aspect, a method for collecting plasma is provided, wherein a plasma product is collected in a plurality of collection phases, between which separated red blood cells are reinfused to a donor. The method of the first aspect comprises: a) Determining the volume of whole blood of a donor(V b ) And hematocrit (Hct); b) Determining the volume of raw plasma (V RP ) The method comprises the steps of carrying out a first treatment on the surface of the c) Determining the volume of plasma product (V PP ) Wherein the plasma product comprises the volume of raw plasma plus the volume of anticoagulant; d) Drawing whole blood from a donor; e) Introducing an anticoagulant into the drawn whole blood at a specific ratio (ACR); f) Separating the drawn whole blood into a plasma product and a second component comprising red blood cells; g) Collecting a plasma product in a plasma collection container; h) Returning the red blood cells to the donor after the desired amount of whole blood has been drawn from the donor; and i) determining Hct and V of the donor prior to each acquisition phase PP 。
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 Until that point.
In a third aspect, a method for collecting plasma is provided, wherein a plasma product is collected in a plurality of collection phases, between which separated red blood cells are reinfused to a donor. The method of the second aspect comprises: a) Determining the volume of whole blood (V) b ) And hematocrit (Hct); b) Based on V b Determining the volume of raw plasma (V RP ) The method comprises the steps of carrying out a first treatment on the surface of the c) Determining to be added to V based on anticoagulant ratio (ACR) and Hct of donor RP Volume V of anticoagulant of (2) AC So that V AC ＝V RP * (ACR (1-Hct)); d) Determining the volume of plasma product (V PP ) Wherein the plasma product comprises a raw plasma volume (V RP ) Volume of anticoagulant (V) AC ) The method comprises the steps of carrying out a first treatment on the surface of the e) Drawing whole blood from a donor; f) Introducing an anticoagulant into the drawn whole blood at a specific ratio (ACR); g) Separating the drawn whole blood into a plasma product and a second component comprising red blood cells; h) Collecting a plasma product in a plasma collection container; i) Returning the red blood cells to the donor after the desired amount of whole blood has been drawn from the donor; and j) determining Hct and V of the donor prior to each acquisition phase PP 。
In a fourth aspect, steps d) to j) are continued until the measurement of the plasma product in the container is collectedVolume of quantity is equal to V PP Until that point.
In a fifth aspect, V b Is determined based on one or more donor-specific characteristics including the weight, height, gender, age, and size of the donor.
In a sixth aspect, a method for acquiring a volume (V during a single acquisition process is provided PP ) Wherein the plasma product is collected in a plurality of collection phases between which the separated red blood cells are reinfused to the donor. In the method of the fourth aspect, V PP Is equal to the volume (V RP ) Added to V during the singulation process RP Anticoagulant (V) AC ) Is a volume of (c). The method comprises the following steps: a) Determining the weight (W) kg ) And gender (M or F); b) Determining a hematocrit (Hct) of the donor; c) Based on the weight of the donor (W kg ) And sex (M or F) determination of the volume V of raw plasma that can be collected RP The method comprises the steps of carrying out a first treatment on the surface of the d) Determining V based on anticoagulant ratio and Hct of donor PP And V is equal to RP The ratio K between such that k=v PP /V RP The method comprises the steps of carrying out a first treatment on the surface of the e) Determining V PP So that V PP ＝V RP * K, performing K; f) Drawing whole blood from a donor; g) Introducing an anticoagulant into the drawn whole blood at a specific ratio (ACR); h) Separating the drawn whole blood into a plasma product and a second component comprising red blood cells; i) Collecting a plasma product in a plasma collection container; j) Returning the red blood cells to the donor after the desired amount of whole blood has been drawn from the donor; and k) determining Hct and target V of the donor prior to each acquisition phase PP 。
In a seventh aspect, steps c) to k) are repeated until the measured volume of plasma product in the collection container is equal to V PP Until that point. Preferably, k=v PP /V RP ＝(ACR*(1-Hct/100)+1)/(ACR*(1-HCT/100))。
In an eighth aspect, a method for acquiring a volume (V during a single acquisition process is provided PP ) Wherein the plasma product is collected in a plurality of collection phases between which separated red blood cells are separatedCells were reinfused to the donor. In this fifth aspect, V PP Is equal to the volume (V RP ) Added to V during the singulation process RP Volume of anticoagulant (V) AC ). The method comprises the following steps: a) Determining the weight (W) kg ) And gender (M or F); b) Determining a hematocrit (Hct) of the donor; c) Based on the weight of the donor (W kg ) And the sex (M or F) of the donor, the volume (V) of the raw plasma that can be collected RP ) The method comprises the steps of carrying out a first treatment on the surface of the d) Determining to be added to V based on anticoagulant ratio (ACR) and Hct of donor RP V of (2) AC So that V AC ＝V RP * (ACR 1-Hct), e) determining V PP So that V PP ＝V RP +V AC The method comprises the steps of carrying out a first treatment on the surface of the f) Drawing whole blood from a donor; g) Introducing an anticoagulant into the drawn whole blood at a specific ratio (ACR); h) Separating the drawn whole blood into a plasma product and a second component comprising red blood cells; i) Collecting a plasma product in a plasma collection container; j) Returning the red blood cells to the donor after drawing the desired amount of whole blood from the donor; and k) determining Hct and V of the donor prior to each acquisition phase PP 。
In a ninth aspect, steps d) to k) are continued until the measured volume of plasma product in the collection container is equal to V PP Until that point.
In a tenth aspect, V RP Is determined by the following means: establishing V for each of a plurality of ranges of donor weight RP And selecting V for a weight range including the weight of the donor RP . The range of donor weights can be divided into three categories: from 110 pounds to 149 pounds, from 150 pounds to 174 pounds, and above 175 pounds.
In an eleventh aspect, V RP ＝K 1 *W kg 。
In a twelfth aspect, V RP Not greater than (1-Hct) (V b ) 28.6% of (C).
In the thirteenth aspect, V b Is determined using one of the Nadler equation, gilcher's five-way method, ICSH's standard, and any other commonly accepted method.
In a fourteenth aspect of the present invention,V RP ＝W kg *10mL/kg。
in a fifteenth aspect, a method for estimating a total blood volume (V b ) V at the time of RP ＝K 2 *V b 。
In a sixteenth aspect, an automated system for separating plasma from whole blood is provided, the automated system comprising reusable hardware components and a disposable kit. The disposable set further comprises: i) A separator for separating whole blood into a plasma portion and a concentrated cell portion, the separator having an input with a blood line integrally connected to the input for transferring whole blood from the donor to the separator, a plasma output port integrally connected through the plasma line to a plasma collection container, and a concentrated cell outlet port integrally connected to a reservoir for receiving concentrated cells prior to reinfusion to the donor; ii) a donor line terminating in a venous puncture needle, the donor line for transferring whole blood from the donor to the blood line; iii) An anticoagulant line integrally connected to the blood line and configured to be connected to an anticoagulant source, the anticoagulant line for delivering anticoagulant to the donor line; iv) a saline water line configured to be attached to a saline source, the saline water line for delivering saline to the blood line; and v) a reinfusion line for transferring the concentrated cells from the reservoir to the donor line. The reusable hardware components further include: i) A peristaltic first pump for delivering anticoagulant into the blood line at a controlled rate during the collection phase; ii) a second pump for delivering anticoagulated whole blood to the separator during the collection phase and returning concentrated cellular components during the reinfusion phase; iii) A third pump for delivering the concentrated cellular component from the separator to the reservoir during the harvesting phase; iv) a clamp associated with each of the blood line, the plasma line, the re-infusion line, and the saline line; v) a weight scale for weighing each of the plasma collection container, the reservoir and the anticoagulant source; and vi) a programmable controller including a touch screen for receiving input from an operator, the programmable controller configured to receive signals from each weight scale and automatically operate the first, second and third pumps and clamps to separate whole blood into a plasma portion and a concentrated cell portion during the harvest phase and to return the concentrated cells to the donor during the reinfusion phase. The programmable controller is further configured to determine a weight of the portion of plasma to be collected in the plasma collection container according to any of the aspects described herein, and the programmable controller is configured to terminate the collection phase upon receiving a signal from the weight scale regarding the plasma collection container that is equal to the weight of the plasma component determined by the controller. In determining the target amount of plasma product to be collected, the controller may be configured to calculate the hematocrit of the donor prior to the collection phase of each cycle. Alternatively or additionally, the controller may receive a signal from a sensor or the like indicative of the hematocrit of the donor. Furthermore, the amount of plasma product in the plasma collection container may be determined by, for example, a weight scale associated with the plasma collection. In one embodiment, the separator comprises a rotating membrane separator.
It is to be understood that the described embodiments are illustrative of some of the applications of the principles of the present subject matter. Many modifications may be made by one of ordinary skill in the art without departing from the spirit and scope of the claimed subject matter, including those combinations of features that are individually disclosed or claimed herein. For these reasons, the scope of the claims is not limited to the above description but is given in the appended claims.
Claims (28)
1. A system for collecting plasma from a donor, the system comprising:
a) A venipuncture needle for withdrawing whole blood from the donor;
b) A blood separator for separating the whole blood into a plasma product and a second blood component comprising red blood cells;
c) A donor line coupled to the venous puncture needle for introducing whole blood from the donor to the blood separator;
d) A first pump for controlling flow through the donor line;
e) An anticoagulant line coupled to an anticoagulant source, the anticoagulant line for combining an anticoagulant with the whole blood;
f) A second pump for controlling flow through the anticoagulant line;
g) A touch screen arranged to receive input from an operator; and
h) A programmable controller configured to:
determining a target volume TVPs of plasma product to be collected based on the weight of the donor, or based on the weight and height of the donor,
determining the percentage% AC of anticoagulant in the target volume of plasma product to be collected based on a predetermined anticoagulant ratio ACR and the hematocrit Hct of the donor TVPP ，
The percentage% AC of anticoagulant in the target volume of plasma product to be collected based on the weight of the donor and based on the predetermined anticoagulant ratio ACR and the hematocrit Hct of the donor TVPP Determining a target volume of pure plasma to be collected
TVP, wherein TVPP = TVP/(1-%ac) TVPP )，
Controlling the system to operate a pumping and return cycle to withdraw whole blood from the donor, adding anticoagulant to the whole blood at a predetermined ratio ACR, separating anticoagulated whole blood into the plasma product and the second component and returning the second component to the donor, and stopping withdrawing whole blood from the donor and starting a final return of the second blood component when a measured volume of plasma product in a plasma collection container reaches the target volume TVPP of plasma product.
2. The system of claim 2, wherein the controller is further programmed to calculate the target volume TVP of pure plasma to be collected as a multiple of the weight of the donor.
3. A system for collecting plasma from a donor, the system comprising:
a) A venipuncture needle for withdrawing whole blood from the donor;
b) A blood separator for separating the whole blood into a plasma product and a second blood component comprising red blood cells;
c) A donor line coupled to the venous puncture needle for introducing whole blood from the donor to the blood separator;
d) A first pump for controlling flow through the donor line;
e) An anticoagulant line coupled to an anticoagulant source, the anticoagulant line for combining an anticoagulant with the whole blood;
f) A second pump for controlling flow through the anticoagulant line;
g) A touch screen arranged to receive input from an operator; and
h) A programmable controller configured to:
determining a total blood volume, TBV, of the donor based on the weight and height of the donor;
Determining a target volume TVP of pure plasma to be collected, which is a certain percentage of the TBV;
determining the percentage% AC of anticoagulant in the target volume of plasma product to be collected based on a predetermined anticoagulant ratio ACR and the hematocrit Hct of the donor TVPP The method comprises the steps of carrying out a first treatment on the surface of the Determining said target volume TVPP of the plasma product, wherein TVPP = TVP/(1-%ac) TVPP ) And (2) and
controlling the system to operate a pumping and return cycle to withdraw whole blood from the donor, adding anticoagulant to the whole blood at the predetermined ratio ACR, separating anticoagulated whole blood into the plasma product and the second component and returning the second component to the donor, and stopping withdrawing whole blood from the donor and starting a final return of the second blood component when a measured volume of plasma product in a plasma collection container reaches the target volume TVPP of plasma product.
4. A system according to claim 3, wherein the controller is further programmed to calculate the total blood volume TBV of the donor based on the weight and the height of the donor to calculate a body mass index BMI of the donor such that TBV = 70/sqrt (BMI/22), wherein BMI = Wt/Ht 2 。
5. A system according to claim 1 or claim 3, wherein ACR is the ratio of the amount of whole blood to the amount of anticoagulant, i.e. ACR = WB/AC, and the controller is further configured to determine the percentage% AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP ＝1/(1+ACR(1-Hct))。
6. A system according to claim 1 or claim 3, wherein ACR is the ratio of whole blood volume plus anticoagulant volume to the anticoagulant volume, acr= (wb+ac)/AC, and the controller is further configured to determine the percent% AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP ＝1/(1+(ACR-1)(1-Hct))。
7. A system according to claim 3, wherein the controller is further programmed to calculate the total blood volume TBV of the donor based on the weight Wt, the height Ht and gender, i.e. male or female, of the donor such that: for men, tbv= (0.3669×ht 3 ) ++ (0.03215×wt) +0.6041, and for females tbv= (0.3561×ht) 3 ) ++ (0.03308 x Wt) +0.1833, wherein Ht is in meters and Wt is in kilograms.
8. A method for collecting a plasma product of a target volume TVPP from a donor, wherein TVPP comprises the target volume TVP of pure plasma plus a volume of anticoagulant, the method comprising:
a) By first calculating the target volume TVP of pure plasma to be collected from the donor as a multiple of the weight of the donor and determining the percent% AC of anticoagulant in the TVPP TVPP To determine TVPP such that TVPP = TVP/(1-%ac) TVPP ) wherein%AC TVPP Is based on an anticoagulant ratio ACR and a hematocrit Hct of the donor;
b) Drawing whole blood from the donor;
c) Mixing an anticoagulant with the whole blood at the anticoagulant ratio ACR;
d) Separating the anticoagulated whole blood into a plasma product, red blood cells, and other cellular components;
e) Collecting the plasma product in a container;
f) Determining a volume VPP of plasma product in the container; and
g) When vpp=tvpp, whole blood withdrawal from the donor is stopped and the red blood cells and the other cellular components are returned to the donor.
9. The method of claim 8, further comprising determining the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP =1/(1+acr (1-Hct)), wherein ACR is the ratio of the amount of whole blood to the amount of anticoagulant, i.e., acr=wb/AC.
10. The method of claim 8, further comprising determining the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP =1/(1+ (ACR-1) (1-Hct)), where ACR is the ratio of whole blood volume plus anticoagulant volume to the anticoagulant volume, i.e., acr= (wb+ac)/AC.
11. The method of claim 8, further comprising: collecting a target volume of TVPP of pure plasma in a plurality of cycles, each cycle comprising a collection phase in which whole blood is drawn from the donor and a return phase in which the red blood cells and the other cellular components are returned to the donor; determining the hematocrit Hct of the donor prior to the acquisition phase of each cycle; and recalculate a target amount TVPP of plasma product to be collected based on the hematocrit Hct of the donor determined prior to the collection phase of each cycle.
12. A method for collecting a plasma product of a target volume TVPP from a donor, wherein TVPP comprises the target volume TVP of pure plasma plus a volume of anticoagulant, the method comprising:
a) By first calculating the total blood volume TBV of the donor based on the weight and height of the donor, calculating a target volume TVP of pure plasma to be collected from the donor as a percentage of TBV, and determining the percentage% AC of anticoagulant in TVPP TVPP To determine TVPP such that TVPP = TVP/(1-%ac) TVPP ) wherein%AC TVPP Is based on an anticoagulant ratio ACR and a hematocrit Hct of the donor;
b) Drawing whole blood from the donor;
c) Mixing an anticoagulant with the whole blood at the anticoagulant ratio ACR;
d) Separating the anticoagulated whole blood into a plasma product, red blood cells, and other cellular components;
e) Collecting the plasma product in a container;
f) Determining a volume VPP of plasma product in the container; and
g) When vpp=tvpp, whole blood withdrawal from the donor is stopped and the red blood cells and the other cellular components are returned to the donor.
13. The method of claim 12, further comprising determining the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP =1/(1+acr (1-Hct)), wherein ACR is the ratio of the amount of whole blood to the amount of anticoagulant, i.e., acr=wb/AC.
14. The method of claim 12, further comprising determining the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP =1/(1+ (ACR-1) (1-Hct)), where ACR is the ratio of whole blood volume plus anticoagulant volume to the anticoagulant volume, i.e., acr= (wb+ac)/AC.
15. The method of claim 12, further comprising: collecting the pure plasma of the target volume TVPP in a plurality of cycles, each cycle comprising a collection phase in which whole blood is drawn from the donor and a return phase in which the red blood cells and the other cellular components are returned to the donor; determining the hematocrit Hct of the donor prior to the acquisition phase of each cycle; and recalculate a target amount TVPP of plasma product to be collected based on the hematocrit Hct of the donor determined prior to the collection phase of each cycle.
16. A system for collecting plasma, the system comprising:
a venous puncture needle configured to withdraw whole blood from a donor;
a blood separator configured to separate the whole blood into a plasma product and a second blood component comprising red blood cells, the blood separator having a plasma output port coupled to a plasma line configured to send the plasma product to a plasma product collection container;
a donor line fluidly coupled to the venous puncture needle, the donor line configured to introduce the whole blood from the donor to the blood separator, flow through the donor line controlled by a first pump;
An anticoagulant line coupled to an anticoagulant source, the anticoagulant line configured to combine anticoagulant with the whole blood from the donor, flow through the anticoagulant line controlled by a second pump;
a touch screen configured to receive input from an operator; and
a controller programmed to control operation of the system, the controller programmed to:
receiving the weight, height and hematocrit of the donor,
percentage% AC of anticoagulant in a target volume of plasma product to be collected determined based on the weight of the donor or based on the weight and height of the donor, based on a predetermined anticoagulant ratio ACR and hematocrit Hct of the donor TVPP And determining a target volume TVPP of the plasma product to be collected based at least on the target volume TVP of the pure plasma to be collected determined by the weight of the donor, wherein TVPP = TVP/(1-%ac) TVPP ) And (2) and
controlling the system to operate a aspirate and return cycle to aspirate whole blood from the donor, 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 and returning the second component to the donor, receiving a current value of the hematocrit Hct of the donor, recalculating the target volume TVPP of plasma product based on the current value of the hematocrit Hct of the donor, and controlling the system to operate a subsequent aspirate and return cycle, thereby accounting for the varying hematocrit of the donor in calculating a new target volume of plasma product to be collected.
17. The system of claim 16, wherein the controller is further programmed to calculate the target volume TVP of pure plasma to be collected as a multiple of the weight of the donor.
18. A system for collecting plasma, the system comprising:
a venous puncture needle configured to aspirate whole blood from a donor;
a blood separator configured to separate the whole blood into a plasma product and a second blood component comprising red blood cells, the blood separator having a plasma output port coupled to a plasma line configured to send the plasma product to a plasma product collection container;
a donor line fluidly coupled to the venous puncture needle, the donor line configured to introduce the whole blood from the donor to the blood separator, flow through the donor line controlled by a first pump;
an anticoagulant line coupled to an anticoagulant source, the anticoagulant line configured to combine anticoagulant with the whole blood from the donor, flow through the anticoagulant line controlled by a second pump;
a touch screen configured to receive input from an operator; and
A controller programmed to control operation of the system, the controller programmed to:
receiving the weight, height and hematocrit of the donor,
determining a target volume TVPP of a plasma product to be collected, a percentage% AC of anticoagulant in the plasma product of the target volume to be collected based on a predetermined anticoagulant ratio ACR and a hematocrit Hct of the donor TVPP A total blood volume TBV of the donor based on the weight and the height of the donor, a target volume TVP of pure plasma to be collected that is a percentage of the TBV, wherein TVPP = TVP/(1-%ac) TVPP ) And (2) and
controlling the system to operate a aspirate and return cycle to aspirate whole blood from the donor, adding an anticoagulant to the whole blood at a predetermined ratio ACR, separating anticoagulated whole blood into the plasma product and the second component, and returning the second component to the donor, receiving a current value of the hematocrit Hct of the donor, recalculating the target volume TVPP of plasma product based on the current value of the hematocrit Hct of the donor, and controlling the system to operate a subsequent aspirate and return cycle, thereby taking into account the varying hematocrit of the donor in calculating a new target volume of plasma product to be collected.
19. The system of claim 18, wherein the controller is further programmed to calculate a total blood volume TBV of the donor based on the weight Wt and the height Ht of the donor to calculate a body mass index BMI of the donor such that TBV = 70/sqrt (BMI/22), wherein BMI = Wt/Ht 2 。
20. The system of claim 16 or claim 18, wherein ACR is a ratio of an amount of whole blood to an amount of anticoagulant, i.e., ACR = WB/AC, and the controller is further configured to determine the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP ＝1/(1+ACR(1-Hct))。
21. The system of claim 16 or claim 18, wherein ACR is a ratio of whole blood volume plus anticoagulant volume to the anticoagulant volume, acr= (wb+ac)/AC, and the controller is further configured to determine the percent AC of anticoagulant in the target volume of plasma product TVPP So that the% TVPP ＝1/(1+(ACR-1)(1-Hct))。
22. The system of claim 18, wherein the controller is further programmed to calculate the total blood volume TBV of the donor based on the weight Wt, height Ht, and gender of the donor, i.e., male or female, such that: for men, tbv= (0.3669×ht3) + (0.03219×wt) +0.6041, and for women, tbv= (0.3561×ht3) + (0.03308×wt) +0.1833, where Ht is in meters and Wt is in kilograms.
23. A system according to claim 16 or claim 18, wherein the controller is programmed to repeat the aspiration phase and the return phase until the target volume of plasma product to be collected is collected, wherein the target volume of pure plasma to be collected is re-determined before each aspiration phase begins.
24. A system according to claim 16 or claim 18, wherein 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 the target volume of plasma product.
25. A system according to claim 16 or claim 18, wherein the controller is programmed to electronically receive a donor parameter from a donor management system to determine a target volume of plasma product based at least in part on the donor parameter.
26. The system of claim 25, wherein the donor management system is programmed to calculate the target volume of plasma product and the controller is programmed to determine the target volume of pure plasma by receiving the target volume of pure plasma from the donor management system.
27. The system of claim 16 or claim 18, wherein the controller is programmed to determine the target volume of plasma product prior to drawing the whole blood from the donor.
28. A system according to claim 16 or claim 18, wherein the controller is further programmed to consider an anticoagulant introduced into the plasma collection container separately from the plasma product.
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| US63/140,534 | 2021-01-22 | ||
| US17/306,099 | 2021-05-03 | ||
| US17/306,099 US11412967B2 (en) | 2018-05-21 | 2021-05-03 | Systems and methods for plasma collection |
| PCT/US2021/033835 WO2022159132A1 (en) | 2021-01-22 | 2021-05-24 | Systems and methods for plasma collection |
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| US20180344921A1 (en) * | 2017-05-30 | 2018-12-06 | Haemonetics Corporation | System and Method for Collecting Plasma |
| CN112105403A (en) * | 2018-05-21 | 2020-12-18 | 汾沃有限公司 | System and method for optimizing plasma collection volume |
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| US20180344921A1 (en) * | 2017-05-30 | 2018-12-06 | Haemonetics Corporation | System and Method for Collecting Plasma |
| CN112105403A (en) * | 2018-05-21 | 2020-12-18 | 汾沃有限公司 | System and method for optimizing plasma collection volume |
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