AUTOMATED COLLECTION SYSTEMS AND METHODS FOR OBTAINING RED BLOOD CELLS, PLATELETS, AND PLASMA FROM WHOLE BLOOD

Abstract: Blood processing systems and methods separate blood drawn from a donor into red blood cells and platelets. The systems and methods operate in a first mode to collect platelets while returning red blood cells to the donor. The systems and methods operate in a second mode to concurrently collect both platelets and red blood cells without returning platelets or red blood cells to the donor.

Description: AUTOMATED COLLECTION SYSTEMS AND METHODS FOR OBTAINING RED BLOOD CELLS, PLATELETS, AND PLASMA FROM WHOLE BLOOD Field of the Invention The invention relates to centrifugal blood processing systems and apparatus. Background of the Invention Certain therapies transfuse large volumes of blood components. For example, some patients undergoing chemotherapy require the transfusion of large numbers of platelets on a routine basis. Manual blood bag systems simply are not an efficient way to collect these large numbers of platelets from individual donors. On line blood separation systems are today used to collect large numbers of platelets to meet this demand. On line systems perform the separation steps necessary to separate concentration of platelets from whole blood m a sequential process with the donor present On line systems establish a flow of whole blood from the donor, separate out the desired platelets from the flow, and return the remaining red blood cells and plasma to the donor, all m a sequential flow loop. Large volumes of whole blood (for example, 2.0 liters) can be processed using an on line system. Due to the large processing volumes, large yields of concentrated platelets (for example, 4 x 10 11 platelets suspended in 200 ml of fluid) can be collected. Nevertheless, a need still exists to further improve systems and methods for collecting cellular-rich concentrates, like red blood cells , from blood components, in a way that lends itself to use in high volume, on line blood collection environments, where higher yields of critically needed cellular blood components like platelets and red blood cells can be realized. Summary of the Invention The invention provides blood processing systems and methods that separate blood drawn from a donor into red blood cells and platelets. The systems and methods operate in first and second modes. In the first operating mode, the systems and methods process whole blood and collect platelets. In the first mode, red blood cells are not concurrently collected, but are returned to the donor . In the second operating mode, the systems and methods process whole blood and concurrently collect red blood cells along with the associated additional volume of platelets. During the second mode, no blood components are returned to the donor . In one embodiment, the systems and methods also operate in a third mode. In the third operating mode, the systems and methods perform a final blood volume trimming function. During the volume trimming function, a portion of the collected red blood cell volume can be returned to the donor. The volume trimming function assures that component volumes actually collected do not exceed the volumes targeted for collection. The invention may be embodied in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the appended claims, rather than in the specific description preceding them. All embodiments that fall within the meaning and range of equivalency of the claims are therefore intended to be embraced by the claims. The invention is not limited to the details of the construction and the arrangements of parts set forth in the following description or shown in the drawings. The invention can be practiced in other embodiments and in various other ways. The terminology and phrases are used for description and should not be regarded as limiting. Brief Description of the Drawings Fig. 1 is a diagrammatic view of an on-line blood processing system; Fig. 2 is a schematic view of a controller that governs the operation of the blood processing system shown in Fig. 1 ,- Fig. 3 is a diagrammatic view of the blood processing system shown in Fig. 1 conditioned by the controller to perform a draw cycle during a non-concurrent collection mode; Fig. 4 is a diagrammatic view of the blood processing system shown in Fig. 1 conditioned by the controller to perform a return cycle during a non-concurrent collection mode; Fig. 5 is a diagrammatic view of the blood processing system shown in Fig. 1 conditioned by the controller to perform a concurrent collection mode; Fig. 6 is a diagrammatic view of the blood processing system shown in Fig. 1 conditioned by the controller to perform a blood volume trimming function; and Fig. 7 is a front view of a blood collection set, which, in use, receives red blood cells after collection in the system shown in Fig. 1 for further processing prior to storage . Description of the Preferred Embodiments Fig. 1 shows in diagrammatic form an on line blood processing system 10 for carrying out an automated blood collection procedure. As illustrated, the system 10 comprises a single needle blood collection network, although a double needle network could also be used. I . System Overview The system 10 includes an arrangement of durable hardware elements, whose operation is governed by a processing controller 18. The hardware elements include a centrifuge 12, in which whole blood (WB) from a donor is separated into platelets, plasma, and red blood cells. A representative centrifuge that can be used is shown in Brown et al U.S. Patent 5,690,602, which is incorporated herein by reference . The hardware elements will also include various pumps, which are typically peristaltic (designated PI to P7) ; and various in line clamps and valves (designated VI to V7) . Of course, other types of hardware elements may typically be present, which Fig. 1 does not show, like sole- noids, pressure monitors, and the like. The system 10 typically also includes some form of a disposable fluid processing assembly 14 used in association with the hardware elements. In the illustrated embodiment, the assembly 14 includes a processing chamber 16 having two stages 24 and 32. In use, the centrifuge 12 rotates the processing chamber 16 to centrifugally separate blood components . The construction of the two stage processing chamber 16 can vary. For example, it can take the form of double bags, like the processing chambers shown and described in Cullis et al . U.S. Patent 4,146,172, which is incorporated herein by reference. Alternatively, the processing chamber 16 can take the form of an elongated two stage integral bag, like that shown and described in Brown U.S. Patent No. 5,632,893, which is also incorporated herein by reference . In the illustrated blood processing system 10, the processing assembly 14 also includes an array of flexible tubing that forms a fluid circuit. The fluid circuit conveys liquids to and from the processing chamber 16. The pumps P1-P7 and the valves VI-V7 engage the tubing to govern the fluid flow in prescribed ways. The fluid circuit further includes a number of containers (designated Cl to C5 ) to dispense and receive liquids during processing. A controller 18 governs the operation of the various hardware elements to carry out one or more processing tasks using the assembly 14. The controller 18 also performs real time evaluation of processing conditions and outputs information to aid the operator in maximizing the separation and collection of blood components. The system 10 can be configured to accomplish diverse types of blood separation processes. Fig. 1 shows the system 10 configured to carry out an automated procedure using a single needle 22 to collect from a single donor (i) a desired yield of concentrated platelets suspended in plasma (PC) (e.g., upwards to two therapeutic units) , which (if desired) can be provided essentially free of leukocytes, (ii) a desired volume of concentrated red blood cells (RBC) (e.g. , upwards to about 200 ml at a hematocrit of about 100% or upwards to about 230 ml at a hematocrit of about 85%) , which (if desired) can also be provided essentially free of leukocytes, and (iii) a desired volume (if desired) of platelet-poor plasma (PPP) . The system 10 can collect various volumes of PC, PPP, and RBC products as governed by applicable regulations for allowable blood volumes. For example, in the United States, component volume iterations that the system 10 can presently provide include, e.g.:(i) one therapeutic unit each of PC, PPP, and RBC, or (ii) one therapeutic unit each of PC and RBC, or (iii) two therapeutic units of PC and one unit of RBC. Further details of the operation of the system 10 to achieve these blood processing objectives will be described later. II. The System Controller The controller 18 carries out the overall process control and monitoring functions for the system 10 as just described. In the illustrated and preferred embodiment (see Fig. 2), the controller comprises a main processing unit (MPU) 44. In the preferred embodiment, the MPU 44 comprises a type 68030 microprocessor made by Motorola Corporation, although other types of conventional microprocessors can be used. In the preferred embodiment, the MPU 44 employs conventional real time multi-tasking to allocate MPU cycles to processing tasks. A periodic timer interrupt (for example, every 5 milliseconds) preempts the executing task and schedules another that is in a ready state for execution. If a reschedule is requested, the highest priority task in the ready state is scheduled. Otherwise, the next task on the list in the ready state is schedule. A. Hardware Control The MPU 44 includes an application control manager 46. The application control manager 46 administers the activation of a library 48 of control applications. Each control application prescribes procedures for carrying out given functional tasks using the system hardware (e.g., the centrifuge 12, the pumps P1-P7, and the valves V1-V7) in a predetermined way. In the illustrated and preferred embodiment, the applications reside as process software in EPROM's in the MPU 44. 7An instrument manager 50 also resides as process software in EPROM's in the MPU 44. The instrument manager 50 communicates with the application control manager 46. The instrument manager 50 also communicates with low level peripheral controllers 52 for the pumps, solenoids, valves, and other functional hardware of the system. As Fig. 2 shows, the application control manager 46 sends specified function commands to the instrument manager 50, as called up by the activated application. The instrument manager 50 identifies the peripheral controller or controllers 52 for performing the function and compiles hardware-specific commands. The peripheral controllers 52 communicate directly with the hardware to implement the hardware- specific commands, causing the hardware to operate in a specified way. A communication manager 54 manages low- level protocol and communications between the instrument manager 50 and the peripheral controllers 52. As Fig. 2 also shows, the instrument manager 50 also conveys back to the application control manager 46 status data about the operational and functional conditions of the processing procedure. The status data is expressed in terms of, for example, fluid flow rates, sensed pressures, and fluid volumes measured. The application control manager 46 transmits selected status data for display to the operator. The application control manager 46 transmits operational and functional conditions to the procedure application Al and the performance monitoring application A2. B. Operator Interface In the illustrated embodiment, the MPU 44 also includes an interactive user interface 58. The interface 58 allows the operator to view and comprehend information regarding the operation of the system 10. The interface 58 also allows the operator to select applications residing in the application control manager 46, as well as to change certain functions and performance criteria of the system 10. The interface 58 includes an interface screen 60 and, preferably, an audio device 62. The interface screen 60 displays information for viewing by the operator in alphanumeric format and as graphical images. The audio device 62 provides audible prompts either to gain the operator's attention or to acknowledge operator actions. In the illustrated and preferred embodiment, the interface screen 60 also serves as an input device. It receives input from the operator by conventional touch activation. Alternatively or in combination with touch activation, a mouse or keyboard could be used as input devices. An interface manager 64 communicates with the interface screen 60 and audio device 62. The interface manager 64, in turn, communicates with the application control manager 46. The interface manager 64 resides as process software in EPROM's in the MPU 44. Further details of the MPU 44 and interface 58 are disclosed in Lyle et al . U.S. Patent 5,581,687, which is incorporated herein by reference. C. System Control Functions In the illustrated embodiment (as Fig. 2 shows), the library 48 includes at least one system control application Al . The system control application Al contains several specialized, yet interrelated utility functions. Of course, the number and type of utility functions can vary. In the illustrated embodiment, a utility function FI derives the platelet yield (Yld) of the system 10. The utility function FI ascertains both the instantaneous physical condition of the system 10 in terms of its separation efficiencies and the instantaneous physiological condition of the donor in terms of the number of circulating platelets available for collection. From these, the utility function FI derive the instantaneous yield of platelets continuously over the processing period. Another utility function F2 relies upon the calculated platelet yield (Yld) and other processing conditions to generate selected informational status values and parameters. These values and parameters are displayed on the interface 58 to aid the operator in establishing and maintaining optimal performance conditions. The status values and parameters derived by the utility function F2 can vary. For example, in the illustrated embodiment, the utility function F2 reports remaining volumes to be processed, remaining processing times, and the component collection volumes and rates. Other utility functions generate control variables based upon ongoing processing conditions for use by the applications control manager 46 to establish and maintain optimal processing conditions. For example, one utility function F3 generates control variables to optimize platelet separation conditions in the first stage 24. Another utility function F4 generates control variables to control the rate at which citrate anticoagulant is returned with the PPP to the donor to avoid potential citrate toxicity reactions. Further details of these and other utility functions can be found in Brown U.S. Patent 5,676,841, which is incorporated herein by reference. A summary of various utility functions relied upon is found at the end of the Specification . Ill . System Operation In the illustrated embodiment, the system 10 is conditioned to achieve at least three processing objectives. The first objective is the collection of a desired yield of concentrated platelets (PC) . The second objective is the collection of a desired volume of PPP to serve as a storage medium for the collected PC. The third objective is the collection of a desired volume of red blood cells (RBC) . Other objectives may be established, e.g., to collect an additional volume of PPP for storage. To achieve these objectives, the utility function FI conditions the system 10 to collect and process blood in at least three different operating modes. In the first operating mode, the system 10 is conditioned to process whole blood and collect PC and PPP. In the first mode, RBC are not concurrently collected, but are returned to the donor. PPP in excess of that desired may also be returned to the donor. In the second operating mode, the system 10 is conditioned to process whole blood and concurrently collect RBC along with the associated additional volumes of PC and PPP. During the second mode, no blood components are returned to the donor. In the third operating mode, the system 10 is conditioned to perform a final blood volume trimming function. During the volume trimming function, a portion of the collected RBC volume, or all or some of the collected PPP volume, or both, can be returned to the donor. The volume trimming function assures that component volumes actually collected do not exceed the volumes targeted for collection. At the outset of the processing procedure, the operator uses the interface 58 to input the desired PC yield to be collected (Yld Goal ) , the desired RBC volume to be collected (RBC Goal ) , and the desired PPP volume to be collected (PPPooa.) • The controller 18 conditions the system 10 to proceed with blood processing in the first operating mode. The controller 18 takes into account two processing variables in commanding a change from the first operating mode to the second operating mode, and from the second operating mode to the third operating mode. The first processing variable is the remaining whole blood volume needed to achieve the desired platelet yield, or Vb rem (in ml) . The second processing variable is the volume of whole blood that is needed to be processed to achieve the desired volume of red blood cells RBC Goal , or Vb RBC . When Vb ret _ = Vb RBC , the controller 18 switches from the first operating mode to the second operating mode. When Vb rem becomes zero, the controller switches from the second operating mode to the third operating mode. (i) Calculating Vb rβm The utility function F2 relies upon the calculation of Yld by the first utility function FI to derive the whole blood volume needed to be processed to achieve Yld Goal During blood processing, the utility function F2 continuously derives the additional processed volume needed to achieve the desired platelet yield Vb rem (in ml) by dividing the remaining yield to be collected by the expected average platelet count over the remainder of the procedure, with corrections to reflect the current operating efficiency η Plt In the illustrated embodiment, the utility function F2 derives this value using the following expression τ . _ 200, ' 000* ( v id G..oal . -YldC.urrent' τ\ ' P D i, t*ACDil χ { Pl tCurrent + Pl P D ost . )' where • YlcL^-- is the desired platelet yield (k/μl), Vb rem is the additional processing volume (ml) needed to achieve Ylcl^^ Yld Cur -. ent is the current platelet yield (k/μl), calculated by the utility function FI based upon current processing values (as set forth m the Summary that follows) η Plt is the present (instantaneous) platelet collection efficiency, which can be calculated based upon current processing values (as set forth m the Summary that follows) . ACDil is an anticoagulant dilution factor (as set forth m the Summary that follows) Plt current is the current (instantaneous) circulating donor platelet count, calculated based upon current processing values (as set forth in the Summary that follows) . Plt Pθ8C is the expected donor platelet count after processing, also calculated based upon total processing values (as set forth in the Summary that follows) . (ii) Calculating Vb RBC The utility function F2 derives Vb RBC based upon RBC Goal , and also by taking into account the donor's whole blood hematocrit (Hct) . The donor's whole blood hematocrit Hct can comprise a value measured at the outset of the procedure, or a value that is sensed on-line during the course of the procedure. In the illustrated embodiment, Hct is not directly measured or sensed. Instead, the controller 18 relies upon an apparent hematocrit value H b of whole blood entering the separation chamber. H b is derived by the controller 18 based upon sensed flow conditions and theoretical consideration. The derivation of H b is described in more detail in the Summary that follows. Based upon H b , the utility function F2 can derive Vb RBC using the following expression: 1 h RB Goal + Buf b where : Buf is a prescribed buffer volume, e.g., 20 ml. In the illustrated embodiment, the utility function F2 provides a further volume buffer, by rounding up the calculated volume of Vb RBC , e.g., to the next highest integer divisible by ten. In the illustrated embodiment, the utility function F2 also compares the calculated value of Vb RBC to a prescribed maximum volume (e.g. , 600 mL) . If Vb RBC equals or exceeds the prescribed maximum, the utility function F2 rounds the value down to a prescribed lesser amount, e.g., to 595 mL. (iii) The First Operating Mode In the first or non- concurrent operating mode, the system 10 processes whole blood and collects PC and PPP for storage. During the first mode, RBC and the uncollected volume of PPP are returned to the donor. The system 10 shown in Fig. 1 employs one, single lumen phlebotomy needle 22. During the non-concurrent mode, the controller 18 operates the system 10 in successive draw and return cycles. During the draw cycle (Fig. 3), the controller 18 supplies the donor's WB through the needle 22 to the chamber 16 for processing. During the return cycle (Fig. 4), the controller 18 returns the RBC and PPP blood components to the donor through the same needle 22. In the illustrated embodiment, the system 10 is configured to enable separation to occur in the chamber 16 without interruption during a succession of draw and return cycles. More particularly, the system 10 includes a draw reservoir 66. During a draw cycle (Fig. 3), a quantity of the donor's WB is pooled in the reservoir 66, in excess of the volume which is sent to the chamber 16 for processing. The system 10 also includes a return reservoir 68. A quantity of RBC collects in the return reservoir 68 during the draw cycle for periodic return to the donor during the return cycle (see Fig. 4) . During the return cycle, WB is conveyed from the draw reservoir 66 to the chamber 16 to sustain uninterrupted separation. In a draw cycle of the non-concurrent mode Fig. 3), the whole blood pump PI direct WB from the needle 22 through a first tubing branch 20 and into the draw reservoir 66. Meanwhile, an auxiliary tubing branch 26 meters anticoagulant from the container Cl to the WB flow through the anticoagulant pump P3. While the type of anticoagulant can vary, the illustrated embodiment uses ACDA, which is a commonly used anticoagulant for pheresis. A container C2 holds saline solution. Another auxiliary tubing branch 28 conveys the saline into the first tubing branch 20, via the in line valve VI, for use in priming and purging air from the assembly 14 before processing begins. Saline solution is also introduced again after processing ends to flush residual components from the assembly 14 for return to the donor. The processing controller 18 receives processing information from a weigh scale 70. The weigh scale 70 monitors the volume of WB collected in the draw reservoir 66. Once the weigh scale 70 indicates that a desired volume of WB is present in the draw reservoir 66, the controller 18 commands the whole blood processing pump P2 to operate to continuously convey WB from the draw reservoir 66 into the first stage 24 of the processing chamber 16 through inlet branch 36. The controller 18 operates the whole blood pump PI at a higher flow rate (at, for example, 100 ml/min) than the whole blood processing pump P2 , which operates continuously (at, for example, 50 ml/min), so a volume of anticoagulated blood collects in the reservoir 66. By monitoring weight using the weigh scale 70, the controller intermittently operates the whole blood inlet pump PI to maintain a desired volume of WB in the draw reservoir 66. Anticoagulated WB enters and fills the first stage 24 of the processing chamber 16. There, centrifugal forces generated during rotation of the centrifuge 12 separate WB into red blood cells (RBC) and platelet-rich plasma (PRP) . A PRP pump P4 operates to draw PRP from the first stage 24 of the processing chamber 16 into a second tubing branch 30 for transport to the second stage 32 of the processing chamber 16. There, the PRP is separated into platelet concentrate (PC) and platelet-poor plasma (PPP). The controller 18 optically monitors the location of the interface between RBC and PRP within the first stage 24 of the processing chamber 16. The controller 18 operates the PRP pump P4 to keep the interface at a desired location within the first stage 24 of the processing chamber 24. This keeps a substantial portion of the leukocytes, which occupy the interface, from entering the flow of PRP. Optionally, the PRP can also be conveyed through a filter F to remove leukocytes before separation in the second stage 32. The filter F can employ filter media containing fibers of the type disclosed in Nishimura et al U.S. Patent 4,936,998, which is incorporated herein by reference. Filter media containing these fibers are commercially sold by Asahi Medical Company in filters under the trade name SEPACEL . The system 10 includes a recirculation tubing branch 34 and an associated recirculation pump P5. The processing controller 18 operates the pump P5 to divert a portion of the PRP exiting the first stage 24 of the processing chamber 16 for remixing with the WB entering the first stage 24 of the processing chamber 16. The recirculation of PRP establishes desired conditions in the entry region of the first stage 24 to provide maximal separation of RBC and PRP. A RBC branch 38 conveys the RBC from the first stage 24 of the processing chamber 16 to the return reservoir 68 (which is controlled by valve V3 ) . A weigh scale 72 monitors the volume of PPP collected in the container C4. A PPP branch 40 conveys PPP from the second stage 32 of the processing chamber 16, by operation of the PPP pump P7. By opening valve V5 , all or a portion of the PPP can be directed to a collection container C4 , depending upon the flow rate of the pump P7. A weigh scale 74 monitors the volume of PPP collected in the container C4. The PPP that is not collected flow into the return reservoir 68, where it mixes with the RBC. During the second operating mode (which will be described later), a relatively large volume of PPP (i.e., from about 50% to 75% of PPP c^ ,) will typically be collected without return to the donor. In anticipation of this, the controller 16 limits the rate at which PPP is collected during the first mode. This avoids the collection of a surplus volume of PPP at the end of the procedure. By limiting the rate at which PPP is collected during the first operating mode, the controller 18 reduces the time of the subsequent blood volume trimming function, thereby reducing the overall procedure time. The small volume of surplus PPP also allows the use of higher return flow rates during the blood volume trimming function, as the amount of anticoagulant (carried in the PPP) that is returned to the donor during the blood volume trimming function is reduced. The controller 18 receives processing information from the weigh scale 72, monitors the volume of RBC and PPP in the return reservoir 68. When a preselected volume exists, the controller 18 shifts the operation of the system 10 from a draw cycle to a return cycle. In the return cycle (Fig. 4), the controller 18 stops the whole blood inlet pump PI and anticoagulant pump P3 and starts a blood return pump P6. A return branch 42 conveys RBC and PPP in the return reservoir 68 to the donor through the needle 22. Meanwhile, while in the return cycle, the controller 18 keeps the WB processing pump P2 , the PRP pump P4, and recirculation pump P5 in operation to continuously process the WB pooled in the draw reservoir 66 through the first stage and second stages 24 and 32 of the chamber 16. When the weigh scale 72 indicates that the contents of the return reservoir 68 have been conveyed to the donor, the controller 18 shifts operation of the system 10 to another draw cycle. The controller 18 toggles between successive draw and return cycles until Vb rera = Vb^. When Vb rem = Vb^,., the controller 18 commands a final return cycle, to return the contents of the return reservoir 68 to the donor. Upon returning the contents of the return reservoir 68, the controller 18 switches from the first operating mode to the second operating mode. (iv) Concurrent Collection Mode In a second or concurrent collection mode (Fig. 5) , the controller 18 conditions to system 10 to operate in a sustained draw cycle, to process whole blood and concurrently collect the targeted volume of RBC, along with associated additional volumes of PC and PPP. During the concurrent collection mode, the controller 18 does not switch operation of the system 10 to a return cycle. There is only one sustained draw cycle during the concurrent collection mode, and no components are returned to the donor . During the sustained draw cycle of concurrent collection mode, the controller 18 avoids the collection of a large surplus volume of whole blood in the draw reservoir 66. In the illustrated embodiment, the controller 18 achieves this objective by maintaining a smaller flow rate differential between the whole blood inlet pump PI and the whole blood processing pump P2 , compared to the differential maintained during the draw cycle of non-concurrent collection mode . For example, in the illustrated embodiment, the whole blood inlet pump PI is operated at a minimal differential of, e.g., only 1 mL/min, above the whole blood processing pump P2. To further assure that only a slight buffer volume of whole blood is maintained in the draw reservoir 66 during the sustained draw cycle of concurrent collection mode, the weight scale 70 toggles the whole blood inlet pump PI and anticoagulant pump P3 off whenever the sensed volume of blood in the draw reservoir 66 exceeds a specified minimum buffer amount , e.g., 5 g. - I I During the sustained draw cycle of concurrent collection mode, red blood cells are directed into a collection container C4 , via the valve V4 , which is opened for this purpose (return valve V3 is closed, so no RBC collect in the return reservoir 68) . A weigh scale 108 monitors the weight of the collection container C4. An associated volume of PC collects in the second stage 32 of the chamber 16, while the associated volume of PPP collects in the collection container C3 (through the operation of the PPP pump P7 and valve V5 , which is opened) . Valve V3 is closed , so no PPP collects in the return reservoir 68. The controller 18 continuously derives Vb rem during the sustained draw cycle of concurrent collection mode. When v b rem becomes zero, the controller 18 terminates the concurrent collection mode. (iv) Blood Volume Trimming Function In the illustrated embodiment (see Fig. 6) , at the end of the concurrent collection mode, the controller 18 assesses the volumes of RBC and PPP that have been collected, using weigh scales 108 and 74, respectively. If the volume of RBC collected exceeds RBC Goal , the controller 18 commands the system 10 to enter a return cycle to return the excess RBC volume to the donor from the collection container C4 , through the branch path 43 (valve V6 being opened) , and into the return path 42 (valve V2 being closed), by operation of the in-line return pump P6. Likewise, if the volume of PPP collected exceeds PPP,-^, the controller 18 commands the system 10 to enter a return cycle to return the excess PPP volume to the donor from the collection container C3 , through the branch path 45 (valve V7 being opened and valve V5 being closed) , and into the return path 42, by operation of the in-line return pump P6. At the end of the blood volume trimming function, the controller 18 commands a saline reinfusion operation to return residual blood in the system 10 to the donor, along with a prescribed fluid replacement volume. (v) Post Collection Processing (1) PPP The retention of PPP can serve multiple purposes, both during and after the component separation process. The retention of PPP serves a therapeutic purpose during processing. PPP contains most of the anticoagulant that is metered into WB during the component separation process. By retaining a portion of PPP instead of returning it all to the donor, the overall volume of anticoagulant received by the donor during processing is reduced. This reduction is particularly significant when large blood volumes are processed. The retention of PPP during processing also keeps the donor's circulating platelet count higher and more uniform during processing. The system 10 can also derive processing benefits from the retained PPP. For example, the system 10 can, in an alternative recirculation mode, recirculate a portion of the retained PPP, instead of PRP, for mixing with WB entering the first compartment 24. Or, should WB flow be temporarily halted during processing, the system 10 can draw upon the retained volume of PPP as an anticoagulated "keep-open" fluid to keep fluid lines patent. In addition, at the end of the separation process, the system 10 can draw upon the retained volume of PPP as a "rinse-back" fluid, to resuspend and purge RBC from the first stage compartment 24 for return to the donor through the return branch 42. (2) PC After the separation process, the system 10 also operates in a resuspension mode to draw upon a portion of the retained PPP to resuspend PC in the second stage 24 for transfer and storage in the collection container (s) C5. Resuspension and transfer of PC to the collection containers C5 can be accomplished manually or on line. Preferable, the container (s) C5 intended to store the PC are made of materials that, when compared to DEHP- plasticized polyvinyl chloride materials, have greater gas permeability that is beneficial for platelet storage. For example, polyolefin material (as disclosed in Gajewski et al U.S. Patent 4,140,162), or a polyvinyl chloride material plasticized with tri-2-ethylhexyl trimellitate (TEHTM) can be used. (2) RBC In the illustrated embodiment (see Fig. 7), a disposable collection set 76 is provided to process the RBC volume collected for storage. The set 76 includes a transfer path 78. The transfer path 78 has a sealed free end 80 designed to be connected in a sterile fashion to a sealed tube segment 82 on the RBC collection container C4 (see Fig. 7) . Known sterile connection mechanisms (not shown) like that shown in Spencer U.S. Patent 4,412,835 can be used for connecting the transfer path 78 to the tube segment 82. These mechanisms form a molten seal between tubing ends, which, once cooled, forms a sterile weld. A first bag 84 communicates with the transfer path 78 through a length of sample tubing 86. The first bag 84 contains a red blood cell additive solution S, e.g., SAG-M or ADSOL ® Solution (Baxter Healthcare Corporation) . Following coupling of the collection set 76 to the RBC collection container C4 , a conventional in-line frangible cannula 106 in the sample tubing 86 is opened, and the red blood cell additive solution S is transferred from the first bag 84 into the collection container C4 for mixing with the collected RBC volume. The mixture of additive solution and RBC can then be transferred back into the first bag 84. Residual air in the first bag 84 can be vented into an in-line air venting chamber 88, which communicates with the transfer path 78. At the same time, an aliquot of the collected RBC volume present in the first bag 84 can be expressed into the sample tubing 86. The tubing 86 preferably carries an identification code 90 which is identical to a code 90 printed on or otherwise applied to the first bag 84. The tubing 86 is then closed with a conventional snap-apart seal, and the first bag 84 is detached from the collection set 76 for storing the RBC volume. The tubing 86 can be further sealed in segments, using conventional tube sealers, to isolate multiple samples of the RBC for analysis and cross-matching. The set 76 also includes a second bag 92, which communicates with the transfer path 78 downstream of the first bag 84 through a branch path 94. The branch path 94 includes an in-line filter 96. The in-line filter 96 carries a filtration medium 98 that selectively removes leukocytes from red blood cells. The filter can comprise, e.g., a R-3000 Red Blood Cell Filter (Asahi Medical) . The mixture of red blood cells and additive solution can be transferred from the collection bag C4 to the second bag 92 through the in-line filter 96, by-passing the first bag 84. In this way, the set 76 provides red blood cells essentially free of leukocytes, suitable for long term storage. An air venting path 100 extends from the second bag 92 to the transfer path 78, bypassing the in-line filter 96. By opening a conventional break-away cannula 106 in the path 100, residual air in the second bag 92 can be vented through the path 100 into the in-line air venting chamber 88. A one-way valve 104 in the path 100 allows air and liquid flow in the path 100 away from the bag 92, but not in the opposite direction. At the same time, an aliquot of the collected RBC present in the second bag 92 can be expressed into the venting path 100. The venting path 100 carries an identification code 102 which is identical to a code 102 printed on or otherwise applied to the second bag 92. The venting path 100 and branch path 94 can be closed with a conventional snap-apart seal, to allow detachment of the second bag 92 from the transfer path 78. The path 100 can also be sealed in segments, to provide multiple samples of the RBC for analysis and cross-matching. The collection set 76 provides the flexibility to provide a red blood cell product suitable for long term storage, which is either non-leukocyte reduced or leukocyte reduced before storage. IV. Summary of Various Processing Utility Functions A. Deriving Platelet Yield The utility function FI makes continuous calculations of the platelet separation efficiency (η Plc ) of the system 10. The utility function FI treats the platelet separation efficiency η Ptl as being the same as the ratio of plasma volume separated from the donor's whole blood relative to the total plasma volume available in the whole blood. The utility function FI thereby assumes that every platelet in the plasma volume separated from the donor's whole blood will be harvested. The donor's hematocrit changes due to anticoagulant dilution and plasma depletion effects during processing, so the separation efficiency η plc does not remain at a constant value, but changes throughout the procedure. The utility function FI contends with these process- dependent changes by monitoring yields incrementally. These yields, called incremental cleared volumes (ΔClrVol) , are calculated by multiplying the current separation efficiency η plc by the current incremental volume of donor whole blood, diluted with anticoagulant, being processed, as follows: Eq ( 1 ) ΔClrVoI -ACDil χ η pl t χ Δ VOL proc where : ΔVol Proc is the incremental whole blood volume being processed, and ACDil is an anticoagulant dilution factor for the incremental whole blood volume, computed as follows: Eq (2) AC ACDil = - AC+ 1 where : AC is the selected ratio of whole blood volume to anticoagulant volume (for example 10:1 or "10") . AC may comprise a fixed value during the processing period. Alternatively, AC may be varied in a staged fashion according to prescribed criteria during the processing period. For example, AC can be set at the outset of processing at a lesser ratio for a set initial period of time, and then increased in steps after subsequent time periods; for example, AC can be set at 6:1 for the first minute of processing, then raised to 8:1 for the next 2.5 to 3 minutes; and finally raised to the processing level of 10:1. The introduction of anticoagulant can also staged by monitoring the inlet pressure of PRP entering the second processing stage 32. For example, AC can be set at 6:1 until the initial pressure (e.g. at 500 mmHg) falls to a set threshold level (e.g. , 200 mmHg to 300 mmHg) . AC can then be raised in steps up to the processing level of 10:1, while monitoring the pressure to assure it remains at the desired level . The utility function FI also makes continuous estimates of the donor's current circulating platelet count (Plt circ ) , expressed in terms of 1000 platelets per microliter (μl) of plasma volume (or k/μl) . Like η P , Plt c . rc will change during processing due to the effects of dilution and depletion. The utility function FI incrementally monitors the platelet yield in increments, too, by multiplying each incremental cleared plasma volume ΔClrVol (based upon an instantaneous calculation of η Plt ) by an instantaneous estimation of the circulating platelet count Plt Cιr . The product is an incremental platelet yield (Δyld) , typically expressed as e n platelets, where e n = .5 x 10" platelets (e 11 = .5 x 10 11 platelets) . At any given time, the sum of the incremental platelet yields ΔYld constitutes the current platelet yield Yld Current , which can also be expressed as follows: Eq (3) ΔClrVolx Pl .. Yld = Yld + — Current Ol d 100 , 000 where : Yld 01d is the last calculated Yld Curren - , and Eq ( 4 ) AClrVolx Pl t , ΔYld= Current 100,000 where : Plt Current is the current (instantaneous) estimate of the circulating platelet count of the donor. ΔYld is divided by 100,000 in Eq (4) to balance units . The following provides further details in the derivation of the above-described processing variables by the utility function FI . (i) Deriving Overall Separation Efficiency η plt The overall system efficiency η plt is the product of the individual efficiencies of the parts of the system, as expressed as follows: Eq (5) r ' lt ~ I ^l3tSe r ^2ndSep ^A c where : li scse i Ξ tne efficiency of the separation of PRP from WB in the first separation stage. rh ndse i s ne efficiency of separation PC from PRP in the second separation stage. r Anc is the product of the efficiencies of other ancillary processing steps in the system. 1. First Stage Separation Efficiency η llItSβp The utility function FI derives η lscSep continuously over the course of a procedure based upon measured and empirical processing values, using the following expression: Eq (6) where : Q b is the measured whole blood flow rate (in ml/min) Q p is the measured PRP flow rate (in ml/min) . H b is the apparent hematocrit of the anticoagulated whole blood entering the first stage separation compartment. H b is a value derived by the utility based upon sensed flow conditions and theoretical considerations. The utility function FI therefore requires no on-line hematocrit sensor to measure actual WB hematocrit . The utility function FI derives H b based upon the following relationship: Eq (7) - H rb h cA Q h -Q ) β„ where : H rbc is the apparent hematocrit of the RBC bed within the first stage separation chamber, based upon sensed operating conditions and the physical dimensions of the first stage separation chamber. As with H b , the utility function FI requires no physical sensor to determine H rbc , which is derived by the utility function according to the following expression: Eq (8) 1 k + 1 H rbc gAKS < *-,- * P > > where: q b is inlet blood flow rate (cm 3 /sec) , which is a known quantity which, when converted to ml/min, corresponds with Q b in Eq (6) . q p is measured PRP flow rate (in cm 3 /sec) , which is a known quantity which, when converted to ml/min corresponds with Q p in Eq (6) . β is a shear rate dependent term, and S γ is the red blood cell sedimentation coefficient (sec) . Based upon empirical data, Eq (8) assumes that β/S γ =15.8xl0 6 sec "1 . A is the area of the separation chamber (cm 2 ) , which is a known dimension. g is the centrifugal acceleration (cm/sec 2 ) , which is the radius of the first separation chamber (a known dimension) multiplied by the rate of rotation squared Ω 2 (rad/sec 2 ) (another known quantity) . k is a viscosity constant = 0.625, and K is a viscosity constant based upon k and another viscosity constant α = 4.5, where: Eq (9) k+2 k + 2 * +1 α v+1 Eq (8) is derived from the relationships expressed in the following Eq (10) : Eq (10) set forth in Brown, The Physics of Continuous Flow Centrifugal Cell Separation, "Artificial Organs" 1989; 13 (1) :4-20) ) . Eq (8) solves Eq (10) for H rbt . 2. The Second Stage Separation Efficiency n 2ndSep The utility function FI also derives η 2ndseP continuously over the course of a procedure based upon an algorithm, derived from computer modeling, that calculates what fraction of log-normally distributed platelets will be collected in the second separation stage 32 as a function of their size (mean platelet volume, or MPV) , the flow rate (Q p ) , area (A) of the separation stage 32, and centrifugal acceleration (g, which is the spin radius of the second stage multiplied by the rate of rotation squared Ω 2 ) . The algorithm can be expressed in terms of a function, which expressed η 2ndseP i- n terms of a single dimensionless parameter gAS p /Q p , where : S p = 1.8 X 10 "9 MPV 2/3 (sec), and MPV is the mean platelet volume (femtoliters, fl, or cubic microns) , which can be measured by conventional techniques from a sample of the donor's blood collected before processing. There can be variations in MPV due to use of different counters. The utility function therefore may include a look up table to standardize MPV for use by the function according to the type of counter used. Alternatively, MPV can be estimated based upon a function derived from statistical evaluation of clinical platelet precount Plt PRE data, which the utility function can use. The inventor believes, based upon his evaluation of such clinical data, that the MPV function can be expressed as: MPV (fl) = 11.5 - 0.009Plt PRE (k/μl) 3. Ancillary Separation Efficiencies η__- c η^- takes into account the efficiency (in terms of platelet loss) of other portions of the processing system. r Anc takes into account the efficiency of transporting platelets (in PRP) from the first stage chamber to the second stage chamber; the efficiency of transporting platelets (also in PRP) through the leukocyte removal filter; the efficiency of resuspension and transferral of platelets (in PC) from the second stage chamber after processing; and the efficiency of reprocessing previously processed blood in either a single needle or a double needle configuration. The efficiencies of these ancillary process steps can be assessed based upon clinical data or estimated based upon computer modeling. Based upon these considerations, a predicted value for η^. can be assigned, which Eq (5) treats as constant over the course of a given procedure. B. Deriving Donor Platelet Count (Plt clr _) The utility function Fl relies upon a kinetic model to predict the donor's current circulating platelet count Plt Cιrc during processing. The model estimates the donor's blood volume, and then estimates the effects of dilution and depletion during processing, to derive Plt c . rc , according to the following relationships: Eq (11) Plt circ = [ {Dilution) χ Plt re ] - (Depletion) where : Plt pre is the donor's circulating platelet count before processing begins (k/μl) , which can be measured by conventional techniques from a sample of whole blood taken from the donor before processing. There can be variations in Plt pre due to use of different counters (see, e.g., Peoples et al . , "A Multi-Site Study of Variables Affecting Platelet Counting for Blood Component Quality Control," Transfusion (Special Abstract Supplement, 47th Annual Meeting), v. 34, No. 10S, October 1994 Supplement). The utility function therefore may include a look up table to standardize all platelet counts ( such as, Plt pre and Pltpost, described later) for use by the function according to the type of counter used. Dilution is a factor that reduces the donor's preprocessing circulating platelet count Plt pre due to increases in the donor's apparent circulating blood volume caused by the priming volume of the system and the delivery of anticoagulant. Dilu tion also takes into account the continuous removal of fluid from the vascular space by the kidneys during the procedure . Depletion is a factor that takes into account the depletion of the donor's available circulating platelet pool by processing. Depletion also takes into account the counter mobilization of the spleen in restoring platelets into the circulating blood volume during processing. 1. Estimating Dilution The utility function Fl estimates the dilution factor based upon the following expression: Eq (12) __ . 2ACD _-___, Pπme+ PPP Dilution=l DonVol where : Prime is the priming volume of the system (ml) . ACD is the volume of anticoagulant used (current or end-point, depending upon the time the derivation is made) (ml) . PPP is the volume of PPP collected (current or goal) (ml) . DonVol (ml) is the donor's blood volume based upon models that take into account the donor's height, weight, and sex. These models are further simplified using empirical data to plot blood volume against donor weight linearized through regression to the following, more streamlined expression: Eq (13) DonVol = 1024 +5lWgt { r 2 =0 . 81 ) where : Wgt is the donor's weight (kg) . 2. Estimating Depletion The continuous collection of platelets depletes the available circulating platelet pool. A first order model predicts that the donor's platelet count is reduced by the platelet yield (Yld) (current or goal) divided by the donor's circulating blood volume (DonVol), expressed as follows : Eq ( 14 ) D _-epl _ = ιoo, ooorid DonVol where : Yld is the current instantaneous or goal platelet yield (k/μl). In Eq (14), Yld is multiplied by 100,000 to balance units. Eq (14) does not take into account splenic mobilization of replacement platelets, which is called the splenic mobilization factor ( or Spl een) . Spleen indicates that donors with low platelets counts nevertheless have a large platelet reserve held in the spleen. During processing, as circulating platelets are withdrawn from the donor's blood, the spleen releases platelets it holds in reserve into the blood, thereby partially offsetting the drop in circulating platelets. The inventor has discovered that, even though platelet precounts vary over a wide range among donors, the total available platelet volume remains remarkably constant among donors . An average apparent donor volume is 3.10 + 0.25 ml of platelets per liter of blood. The coefficient of variation is 8.1%, only slightly higher than the coefficient of variation in hematocrit seen in normal donors. The mobilization factor Spleen is derived from comparing actual measured depletion to Depl (Eq (14) ) , which is plotted and linearized as a function of Plt Pre . Spleen (which is restricted to a lower limit of 1) is set forth as follows: Eq (15) Spleen= [2.25-0.004Plt pre ] ≥l Based upon Eqs (14) and (15) , the utility function derives Depletion as follows: Eq (16) C . Real Time Procedure Modif ications The operator will not always have a current platelet pre-count Plt Pre for every donor at the beginning of the procedure. The utility function Fl allows the system to launch under default parameters, or values from a previous procedure. The utility function Fl allows the actual platelet pre-count Plt Pre , to be entered by the operator later during the procedure. The utility function Fl recalculates platelet yields determined under one set of conditions to reflect the newly entered values. The utility function Fl uses the current yield to calculate an effective cleared volume and then uses that volume to calculate the new current yield, preserving the platelet pre-count dependent nature of splenic mobilization. The utility function Fl uses the current yield to calculate an effective cleared volume as follows: Eq (17) 100 , OOO xDonVoIx Yld,. ClrVol= - r _ -. - _. . /irl-.Ln f PfPfP 50 , ' 000* Yld current [DonVol - Prime- + ] xPre-, -■ Spleen 01d where : ClrVol is the cleared plasma volume. DonVol is the donor's circulating blood volume, calculated according to Eq (13) . Yld^,.-,.- is the current platelet yield calculated according to Eq (3) based upon current processing conditions . Prime is the blood- side priming volume (ml) . ACD is the volume of anticoagulant used (ml) . PPP is the volume of platelet-poor plasma collected (ml) . Pre 01d is the donor's platelet count before processing entered before processing begun (k/μl) . Spleen 01d is the splenic mobilization factor calculated using Eq (16) based upon Pre 01d . The utility function Fl uses ClrVol calculated using Eq (17) to calculate the new current yield as follows: Eq (18) where : Pre New is the revised donor platelet pre-count entered during processing (k/μl) . Yld New is the new platelet yield that takes into account the revised donor platelet pre-count Pre New . ClrVol is the cleared plasma volume, calculated according to Eq (17) . DonVol is the donor's circulating blood volume, calculated according to Eq (13) , same as in Eq (17) . Prime is the blood- side priming volume (ml) , same as in Eq (17) . ACD is the volume of anticoagulant used (ml) , same as in Eq (17) . PPP is the volume of platelet-poor plasma collected (ml) , same as in Eq (17) . Spleen Neu is the splenic mobilization factor calculated using Eq (15) based upon Pre New . D. Remaining Procedure Time The utility function F2 can also calculate remaining collection time (t rem ) (in min) as follows: Eq (19) , _ Vbrem rem Q b where : Vb_ m is the remaining volume to be processed, calculated using Eq (19) based upon current processing conditions . Qb is the whole blood flow rate, which is either set by the user or otherwise derived by the controller 18. E. Plasma Collection The utility function F2 adds the various plasma collection requirements to derive the plasma collection volume (PPP^.-) (in ml) as follows: Eq(20) PPP r Goal = PPP PC+ PPP S B ource +PPP R D ei .πf f use + PPP W.,as ,te + PPP r C.ol l l l Ct h iam where : PPPp c i Ξ tne platelet-poor plasma volume selected for the PC product, which can have a typical default value of 250 ml, or be otherwise calculated by the controller 18 based upon current processing conditions. PPP Sour _ e is the platelet-poor plasma volume selected for collection as source plasma. PPP Waste is the platelet-poor plasma volume selected to be held in reserve for various processing purposes (Default = 30 ml) . PPP Collcham is the volume of the plasma collection chamber (Default = 40 ml) . PPP Reιn£use is the platelet-poor plasma volume that will be reinfusion during processing. F. Plasma Collection Rate The utility function F2 calculates the plasma collection rate (Q PPP ) (in ml/min) as follows: Eq (21) _ PPP r Goal , - PPPCurrent rem where : ppp ooa i is tne desired platelet-poor plasma collection volume (ml) . PPP Curr . nt is the current volume of platelet-poor plasma collected (ml) . t rem is the time remaining in collection, calculated using Eq (19) based upon current processing conditions . G. Total Anticipated AC Usage The utility function F2 can also calculate the total volume of anticoagulant expected to be used during processing (ACD End ) (in ml) as follows: Eq (22) where : ACD Cu _ rent is the current volume of anticoagulant used (ml) . AC is the selected anticoagulant ratio, Q b is the whole blood flow rate, which is either set by the user or otherwise calculated by the controller 18 based upon current processing conditions. t rem is the time remaining in collection, calculated using Eq (19) based upon current processing conditions. Various features of the inventions are set forth in the following claims.

Claims: We claim : 1. A blood processing system comprising a separation chamber operating to separate blood drawn from a donor into red blood cells and platelets, and a controller operative in a first mode to collect platelets while returning red blood cells to the donor and in a second mode to collect platelets and red blood cells without returning platelets or red blood cells to the donor. 2. A blood processing system according to claim 1 wherein the separation chamber operates to separate plasma essentially free of platelets from the blood, and wherein, in the first mode, at least a potion of the plasma essentially free of platelets is returned to the donor and, in the second mode, all of the plasma essentially free of platelets is collected and not returned to the donor . 3. A blood processing system according to claim 1 further including a single needle to draw and return blood to the donor. 4. A blood processing system according to claim 1 further including an element to remove leukocytes from platelets. 5. A blood processing system according to claim 1 further including an element to remove leukocytes from red blood cells. 6. A blood processing system according to claim 1 further including a source of a blood additive solution for mixing with red blood cells. 7. A blood processing system according to claim 1 further including an input to set a desired yield of platelets for the first and second modes. 8. A blood processing system according to claim 1 further including an input to set a desired yield of red blood cells for the second mode. 9. A blood processing system according to claim 1 wherein the controller is operable in a third mode to return a portion of the red blood cells collected during the second mode to the donor to achieve a desired yield of red blood cells. 10. A blood processing method comprising the steps separating blood drawn from a donor into red blood cells and platelets, and operating in a first mode to collect platelets while returning red blood cells to the donor, and operating in a second mode to concurrently collect both platelets and red blood cells without returning platelet concentrate or red blood cells to the donor. 11. A blood processing method according to claim 10 further including the step of separating plasma essentially free of platelets from the blood, and wherein, in the first mode, at least a potion of the plasma essentially free of platelets is returned to the donor and, in the second mode, all of the plasma essentially free of platelets is collected and not returned to the donor . 12. A blood processing method according to claim 11 and further including the step of resuspending the platelets collected during the first and second modes with at least a portion of the plasma essentially free of platelets collected. 13. A blood processing method according to claim 10 and further including the step of using a single needle to draw and return blood to the donor. 14. A blood processing method according to claim 10 and further including the step of removing leukocytes from platelets collected during the first and second modes. 15. A blood processing method according to claim 10 and further including the step of removing leukocytes from red blood cells collected during the second mode. 16. A blood processing method according to claim 10 and further including the step of mixing a blood additive solution with the red blood cells collected during the second mode . 17. A blood processing method according to claim 10 and further including setting a desired yield of platelets for the first and second modes. 18. A blood processing method according to claim 10 and further including setting a desired yield of red blood cells for the second mode. 19. A blood processing method according to claim 10 and further including the step of operating in a third mode to return a portion of the red blood cells collected during the second mode to the donor to achieve a desired yield of red blood cells. 20. A blood processing assembly comprising a main path attached to a source of blood, a first branch path coupled to the main path including a collection container that holds a blood additive solution, a second branch path coupled to the main path downstream of the first branch path and including a second collection container, and a leukocyte removal filter in the second branch path . 21. A blood processing assembly according to claim 20 and further including a vent path coupled to the second collection container and the main path for venting air from the second collection container in a path that bypasses the leukocyte removal filter.

Inventors: BLICKHAN BRYAN J, DUNCAN TAMMY, FOLEY JOHN T, NAYAK ABINASH, PATNO TIMOTHY J, PIERCE JENNIFER A, STINAFF RUSSELL D, WEBER MARK, BLICKHAN, BRYAN, J., DUNCAN, TAMMY, FOLEY, JOHN, T., NAYAK, ABINASH, PATNO, TIMOTHY, J., PIERCE, JENNIFER, A., STINAFF, RUSSELL, D., WEBER, MARK
Applicants: BAXTER INT, BAXTER INTERNATIONAL INC.
Application year: 2000
Main classification: A61M37
IPC codes: A61M1, G01N33