CA2195071A1

CA2195071A1 - System for deriving collected blood storage parameters

Info

Publication number: CA2195071A1
Application number: CA002195071A
Authority: CA
Inventors: Richard I. Brown
Original assignee: Individual
Current assignee: Baxter International Inc
Priority date: 1995-06-07
Filing date: 1996-05-22
Publication date: 1996-12-19
Also published as: EP0775009A1; JP3955999B2; AU5935996A; DE69633768D1; WO1996040405A1; ES2231810T3; JPH10503696A; US5639382A; AU692711B2; NO970542D0; EP0775009A4; EP0775009B1; DE69633768T2; NO970542L

Abstract

Systems and methods recommend storage parameters for a prescribed number of platelets in a prescribed number of gas permeable containers (C3) and in association with a specified storage medium. The systems and methods receiving as input selected storage criteria information. The systems and methods generate as output, based upon the selected storage criteria information received, recommended storage parameters comprising a recommended number of selected storage containers (C3) to be used and a recommended volume of storage medium to be used.

Description

21 9~7 1 W O 96/40405 1 PC~rAUS96/07809 "System For Deriving Collected Blood Storage Parameters"

Field of th- rnvention S The invention generally relates to blood processing systems and methods.
Baqk~L~u~d of the Invention Today people routinely separate whole blood by centrifugation into its various theL~peu~ic , such as red blqod cells, platelets, and plasma.
Certain therapies transfuse large volumes of blood ~ -ntS. 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 n~ A y to separate ~..c~ tion of platelets from whole blood in a sequential process with the donor present. on line sy~tems establish a flow of whole blood from the donor, e , -~te out the desired platelets from the flow, and return the 1~ ;ning red blood cells and plasma to the donor, all in a sequential flow loop.
Large volumes of whole blood (for example, 2.0 liters) can be pLocL3sed using an on line 2 l 9 ~

system. Due to the large processing volumes, large yields of uoncO..LL~ted p:Latelets (for example, 4 x 101~ platelets sncpAn~pd in 200 ml of fluid) can be collected. NULeJ~OL~ since the donor's red blood cells are lcLuLI.ed, the donor can donate uhole blood for on line processing much more fLo~u6l~-1y than donors for procpcc;nAi in multiple blood bag systems.
Nevertheless, a need still exists for further ; oved systems and methods for collecting cellular-rich cuncellLL_tes from blood _ L~ in a way that lends itself to use in high volume, on line blood collection environments, where higher yields of critically needed cellular blood ~ ~ Ls like platelets can be realized.
As the operational and performancO demands upon such fiuid procAcf:;ng sy_tems become more complex and sophisticated, the need exists for automated process contro:Llers that can gather and generate more detailed information and control signals to aid the Up-oL~tUl in r-Y;mi~;ng processing and separation efficiPn~AiPc Eg~ rv of th~ Tnvent~on The invention provides systems and methods that, based upon storage criteria inputs, generate ~c- -~dP~ storage parameters for a given blood _At. The Lo_ -'Ad storage parameters comprise the ~ ' number of storage containers (Plt~C) to be used, a_ well as the ~~- -n~P~ volume of stc,rage medium (Plt~D) to be used.
In a preferred : '~';- t, the l~ '-' storage parameters pertain to platelets. In this ~-~o~; L, the storage criteria inputs include a value c~pLeaen-ing the number OA~ platelets to be stored (Yld)(in k/~l); 21 value 1~PL~ ~ d ing the ~ W O 96/40405 ~ P~rAU596/07809 measured mean platelet volume of the platelets to be stored (MPV)(in fl); a ta,~Led platelet volume for the sPlP~tPd container (PltT~) (in ml), which takes into account the gas peL - hil ity of the selected container; and a desired th~ _y~ocrit (Tct), e~Le~ned as a pe~e.,t~ge, for the platelets during storage.
In a preferred pmho~ t, the systems and methods derive the volume of platelets to be stored (Plt~) (in ml) in the following way:
PltVoL=Yld X MPV

In this ~ , the systemS and methods also derive a number value BAG as follows:
Plt Pl t~,,o, In this ~'i ~, PltU~ ~ 1 when BAG S 1.
Otherwise PltUG = tBAG + 1], where tBAG + 1] i8 the integer part of the ~uantity tBAG + 1].
In this ~ ho~ ,, PtlMED (in ml) i8 calculated as follows:
Pl~
Pl th~d- vo In a preferred '~';- ~, the storage medium is plasma. In r~ -~'ing the storage parameters for platelets, the systems and methods taXe into account the buffering effect Or h;~,..1.~.. ~te in the plasma to keep the pH at a level to sustain platelet viability during storage. The systems and methods also take into efrect the 2 l 9507 1 W O 96/40405 PC~r/U596/07809 partial ~.~s~e of oxygen of platelets to keep the platelets outside an anaerobic state during storage.
In this way, the systems and methods derive optimal storage conditions to su!;tain platelets during the PYpected storage period.
The various asplscts of the invention are P~pP~i~lly well suited for on line blood separation processes.
Other features and advantages of the invention will become apparent from the following description, the drawings, and the claims.
~ri~f D~crintion o~ the DrawinqJ
Fig. 1 is a diagrammatic view of a dual needle platelet collection system that includes a controller that ~ the features of the invention;
Fig. 2 is a dia~ tic flow chart view of the controller and associated system optimization application that ~~';PS the features of the invention;
Fig. 3 is a dlia~- tic view of the function utilities contained within the system optimization application shown in Pig. 2;
Fig. 4 is a diagrammatic flow chart view of the utility function contained within the system optimization application that derives the yield of platelets during a given procP~ing session;
Fig. 5 is a diagrammatic flow chart view of the utility f~nrti~n~ contained within the system optimization application that provide procpc~ing status and parameter information, generate control variables for achieving optimal separation efficiencies, and generat:e control variables that control the rate of citrat:e infu~ion during a given 35 procP~l ng gession;

~ WO 96140405 PCT/US96/07809 Fig. 6 is a diagrammatic flow chart view of the utility function contained within the system optimization application that rPc ~- optimal storage p~L PrS based upon the yield of platelets during a given processing session;
Fig. 7 is a diagrammatic flow chart view of the utility function contained within the system optimization application that estimates the proc~Ccing time before . -ing a given processing session;
Fig. 8 is a graphical depiction of an algorithm used by the utility function shown in Fig.
4 expressing the relationship between the efficiency of platelet separation in the second stage chamber and a dimensionless parameter, which takes into account the size of the platelets, the plasma flow rate, the area of the chamber, and the speed of rotation;
Fig. 9 is a graph showing the relationchip between the partial pL~s~e of oxygen and the permeation of a particular storage container, which the utility function shown in Fig. 6 takes into account in r~ -i ng optimal storage parameters in terms of the number of storage containers;
Fig. 10 is a graph showing the relationship between the c~ ion of bicarbonate and storage U~ ~ ocrit for a particular storage container, which the utility function shown in Fig. 6 takes into account in ~- ~ing optimal storage p-~L Prs I n terms of the volume of plasma storage medium; and Fig. 11 is a graph showing the efficiency of platelet separation, e~y.~~-e1 in terms of mean platelet volume, in terms of inlet hematocrit, which a utility function shown in Fig. 5 takes into W O 96/40405 PC~r~US96/07809 account in generating a control variable governing plasma recirculation during pro~Pas;ng.
The various aspects of the invention may be : ';P~ in several forms without departing from its spirit or essential characteristics. The scope of the invention is defined in the AppPn~Pd claims, rather than in the speciLfic description preceding them. All : ' 'i- ~~ that fall within the me4ning and range of et~uivalency of the claims are therefore intended to be embraced by the claims.
De wrlption of t4e Prererrtld E ~ Ls Fig. 1 shows in diagrammatic form an on line blood processing system 10 for carrying out an automated platelet collection PI ucedu,e. The system 10 in many respects typifies a conventional two needle blood collection network, although a convention single needle network could also be used.
The system 10 in~lu~o~ a proceasing controller 18 embodying the features of the invention.
I. T4c ~ ration 8v~t~
The system 10 includes an aLL~, L of durable hardware e~ L~j, whose operation is ~uv~L..ed by the procP~ing controller 18. The ha~, ~ el~ LS include a centrifuge 12, in which whole blood tWB) is s~uat~ted into its various UI~L~ ULiC ~ - ts, like platelets, plasma, and red blood cells (F~BC). 'rhe hardware P1A LY will also include various pumps, which are typically peristaltic tdesignated ~Pl to P4); and various in line clamps and valves l~designated Vl to V3). Of course, other types of hardware ~l ~s may typically be present, which Fig. 1 does not show, like solenoids, ~D~ur~ monitors, and the like.
The system 10 ty~pically also includes some form of a d~aroc~hle fluid procPasing assembly 14 -21 95~71 ~\ WO 96/40405 PCT/lJS96/07809 . ~ .
used in association with the hardware elements.
In the illustrated blood processing system 10, the assembly 14 includes a two stage processing chamber 16. In use, the centri~uge 12 rotates the S processing chamber 16 to centrifugally separate blood ~ Ls. A Ie~ enLative centrifuge that can be used is shown in willii et al U.S. Patent 5,360,542, which is ir.~o~uL~ted herein by reference.
The construction of the two stage process-ing chamber 16 can vary. For example, it can take the form of double bags, like the processing chambers shown in Cullis et al. U.S. Patent 4,146,172. Alternatively, the procPacing chamber 16 can take the form of an elongated two 5tage integral bag, like that shown in ~rown U.S. Patent No.
5,370,802.
In the illustrated blood proc~~c1ng system 10, the procaqclng assembly 14 also in~lu~ an array of ~lexible tubing that forms a fluid circuit.
The fluid circuit conveys liquids to and from the proce~sing chamber 16. The pumps Pl-P4 and the valves Vl-V3 engage the tubing to govern the ~luid rlow in prescribed ways. The fluid circuit further incln~ a number of containers (designated Cl to C3) to d;~p~n~e and receive liquids during ~ocess-ing.
The controller 18 governs the operation of the various hardware ~1 L5 to carry out one or more processing tasks using the assembly 14. The controller 18 also performs real time evaluation of proc~ing conditions and outputs information to aid the operator in r-~imi 7ing the separation and collection of blood ~ ~ Ls. The invention specifically ~ ..s important attributes o~ the 21 9507~

controller 18.
The system 10 c~m be configured to accom-plish diverse types of blood separation pL oce~ses.
Fig. 1 shows the system :L0 configured to carry out an automated two needle platelet collection proce-dure.
In a collection mode, a first tubing branch 20 and the whole blood inlet pump P2 direct WB from a draw needle 22 into the first stage 24 of the processing chamber 16. M-An~hile~ an al~YiliA~y tubing branch 26 meter~ anticoagulant from the container C1 to the WB flow through the antico-agulant pump Pl. While the type of anticoagulant can vary, the illustrated : -'i uses ACDA, which is a commonly used anticoagulant for pheresis.
The container C2 holds saline solution.
Another AllYi 1 i Ary tubinc3 branch 28 conveys the saline into the first tubing branch 20, via the in line valve Vl, for use in priming and purging air from the system 10 before prc)~csing begins. Saline solution is also inLL~du~ed again after proc~sing ends to flush residual e _ ~~ts from the assembly 14 for return to the donor.
Anticoagulated ~ enters and fills the first stage 24 of the proceQQin7 chamber 24. There, centrifugal forces generat:ed during rotation of the centrifuge 12 separate WB into red blood cells (RBC) and platelet-rich plasma tPRP).
The PRP pump P4 operates to draw PRP from the first stage 24 of thelprocessing cha~ber 16 into a second tubing branch 30 for L~n ~r L to the second stage 32 of the proceqcing chamber 16.
There, the PRP is separated into platelet c~nc~....... ......Lr~te (PC) and platelet-poor plasma (PPP).
Optionally, the PRP can be c~ y.d through ~ 1 9507 1 ~ W096/40405 PCT~596/07809 _ g _ .e . .
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 ~iccl OSDd in Nishimura et al U.S. Patent 4,936,998, which is 5 incoL~o~ted herein by reference. Filter media containing these fibers are commercially sold by Asahi Medical Company in filters under the trade name SEPACELL.
The system 10 includes a recirculation tubing branch 34 and an associated recirculation pump P3. The processing controller 18 operates the pump P3 to divert a portion of the PRP exiting the first stage 24 of the procDCcing chamber 16 for remixing with the WB entering the first stage 24 of the pro~DCcing chamber 16. The recirculation of PRP
estAhlichDc desired conditions in the entry region of the first stage 24 to provide maximal separation of RBC and PRP.
As WB is drawn into the first chamber stage 24 for separation, the illustrated two needle system simultaneously returns RBC from the first chamber stage 24, along with a portion of the PPP from the second chamber stage 32, to the donor through a return needle 36 through tubing bL~ I.es 38 and 40 and in line valve V2.
The system 10 also collects PC (~ d in a volume of PPP) in some of the containers C3 through tubing branches 38 and 42 and in line valve V3 for storage and beneficial use. Preferable, the c~ntAin~r(s) C3 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 tas ~icrlo~ed in Gajewski et al U.S. Patent 4,140,162), 2~ ~507i W O 96/40405 PC~rnUS96/07809 or a polyvinyl chloride material plasticized with tri-2-ethylhexyl trimellitate (TE~TM) can be used.
The system 10 can also collect PPP in some of the containers C3 through the same fluid path.
The continuous retention of PPP serves multiple ~yo6es, both during and after the _n~.-L
separation process.
The retention of PPP serves a therapeutic purpose during processing. PPP c~n~A i n~ most of the anticoagulant that is metered into WB during the ; L 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 ~L ocessed. The retention of PPP during processing also keeps the donor's circulating platelet count higher and more uniform during prOCP':E i nq .
The system lo can also derive processing benefits from the retained PPP.
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 an~i~oa~lated "ke~ en" fluid to keep fluid lines patent. In addition, at the end of the separation process, the system lO draws upon the retained volume of PPP as a "rinse-back" fluid, to rDs~pPn~ and purge RBC from the first stage compartment 24 for return to the donor through the return branch 40. After thle separation process, the system lO also operates i.n a r~7-~l, Rion mode to I

=

~ WO 96/40405 -- 11 PCT/US96/07809 .~ .
draw upon a portion of the retained PPP to r~Ucp~n~
PC in the second compartment 24 for transfer and storage in the collection container(s) C3.
II. The 8v~tam Controller The controller 18 carries out the overall process control and monitoring functions for the system 10 as just described.
In the illuDL~ted and preferred ~mho~l- L
(see Fig. 2), the controller comprises a main procaCcing unit (MPU) 44. In the preferred embodi-ment, the MPU 44 comprises a type 68030 mi~Lu~rocessvr made by Motorola Corporation, although other types of conventional mi~L~rocesD~,D
can be used.
In the preferred : ~ 'ir L~ the MPU 44 employs conventional real time multi-tasking to allocate NPU cycles to proc~RR~ i ng tasks. A periodic timer interrupt (for example, every 5 mi 11 iR~cAn~Q) preempts the executing task and ~r~ R another that is in a ready state for execution. If a r~cch~ le i8 requested, the highest priority task in the ready state is srh~ ed. Otherwise, the next task on the list in the ready state is schedule.
A. Fun~tional ~arduar- Control The MPU 44 incl~ Q an application control manager 46. The application control manager 46 administers the activation of a library 48 of control applications (designated Al to A3). Eaoh control application Al-A3 prescribes pLoced~L.8 for carrying out given fllnr~j~n~l tasks using the system hardware (e.g., the centrifuge 12, the pumps P1-P4, and the valves V1-V3) in a prr~t~rmin~d way. In the illustrated and preferred . ~ L, the applica-tions Al-A3 reside as process sofL~Le in EPROM's in W096/40405 - 12 - PCT~S96/07809 the MPU 44.
The number of applications A1-A3 can vary.
In the illustrated and preferred : ' -;r-nt, the library 48 includes at least one clinical ~Lucedure application Al. The procedure application A1 contains the steps to carry out one prescribed clinical procesBing ~ro~edu~. For the sake of example in the illustrated '-'; L, the library 48 inr~ a p~OCedULe application Al for carrying out the dual needle platelet collection process, as already generally described in connection with Fig.
1. Of course, additional ~Lou~du~è applications can be, and typically will be, incln~d. For example, the library 48 can include a pIoceduL~ application for carrying out a conventional single needle platelet collection process.
In the illustrated and preferred o~;- L, the library 48 also includes a system optimization application A2. The system optimization application A2 contains interrelated, 5per;Ali7sd utility 1unctions that process information based upon real time processing conditions and empirical estimations to derive information and control variables that optimize system performance. Further details of the opt;~; 7~tion application A.2 will be described later.
The library 48 illso inr~ es a main menu application A3, which coordinates the selection of the various applications Al-A3 by the OpeL~tUL~ as will also be described in greater detail later.
Of course, additional non-rlin;rAl pLoceduLè applications czm be, and typically will be, included. For example, the library 48 can include a configuration application, which contains the ~LucéduL~l for allowing th~ U~_L~UL to 21 9507l ~ W096/40405 - 13 - PCT~S96107809 . .
configure the default operating parameters of the system 10. As a further example, the library 48 can include a diagnostic application, which contains the pL~ce~uLes aiding service personnel in diagnosing and troubleshooting the functional integrity of the system, and a system restart application, which performs a full restart of the system, should the system become unable to manage or recover from an error condition.
An ir.~L~, t manager 50 also resides as process software in EPROM's in the MPU 44. The ir,~L-, L manager 50 - ic~tes with the application control manager 46. The in~-L, manager 50 also c icAtes with low level peripheral controllers 52 for the pumps, solenoids, valves, and other fllnr~lo~Al hardware of the system.
As Fig. 2 shows, the application control manager 46 sends specified function n~ to the innLL, L manager 50, as called up by the activated application Al-A3. The inDLLI L manager 50 identifies the peripheral controller or controllers 52 for performing the function and compiles hard-ware-specific ~ '~. The peripheral controllers 52 1rAte directly with the hardware to implement the haL, -e ~ecific '-, causing the hardware to operate in a specified way. A
ication manager 54 manages low-level protocol and ~ lrations between the ir.n-L, L manager 50 and the peripheral controllers 52.
As Fig. 2 also shows, the ir~LL, manager 50 also conveys back to the application control manager 46 status data about the operational and functional conditions of the processing pI ocedu~. The status data is e~ 3sed in terms of, for example, fluid flow rates, sensed ~L~nu~s~

wog6/4040s - 14 - pcT~s96lo78os -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 p,o~eduLe application A1 and the performance monitoring application A2.
B. U~-r ~:nterfac- Control In the illustralted ~ t, the MPU 44 also inrlll~P~ an interactiive 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 ~nrln~P~ an interface screen 60 and, preferably, an audio device 62. The interface screen 60 dispLays information for viewing by the operator in alpha-numeric format and as graphical images. The audio device 62 provides audible prompts either to gain the operator's attention or to acknowledlge operator actions.
In the illustrated and preferred 'c~i- -t, the interface screen 60 also serves as an input device. It receives input from the U~ UL by conventional touch activation. Alterna-tively or in combination with touch activation, a mouse or keyboard could be used ag input devices.
An interface controller 64 _ i~ates with the interface screen 60 and audio device 62.
The interface controller 64, in turn, ~_ icates with an interface manager 66, which in turn COD unicates with the ap~plication control manager ~l 95071 ~ PCT/U596/07809 _ WO 96/40405 ~ 15 ~

, 46. The interface controller 64 and the interface manager 66 reside as process software in EPROM's in the MPU 44.
Further details of the interface 58 are 5 ~i~closed in cop~n~ing application Serial No. xxx.
C. Th~ 8y3tem optimization Appllc-tion In the illustrated embodiment (as Fig- 3 shows), the system optimization application A2 contains six specialized yet interrelated utility functions, designated Fl to F6. Of course, the number and type of utility functions can vary.
In the illustrated : -~ir L~ a utility function Fl derives the yield of the system 10 for the particular c~lnlAr ~ ~IL targeted for collection. For the platelet collection pLucel~Le application A1, the utility function F1 ascertains both the instantaneous physical condition of the system 10 in terms of its separatlon effini~nci~q and the ins~AntAn~ol~q physiological condition of the donor in terms of the number of circulating platelets available for coll~r~iAn. From these, the utility function F1 derive the instantaneous yield of platelets con~inu~llqly over the processing period.
Yet another utility function F2 relies upon the calculated platelet yield and other processing conditions to 9elleL~e sP7~rted informational status values and paL Le~ S . These values and parameters are displayed on the interface 58 to aid the operator in es~Ahli~hing and maintaining optimal performance conditions. The status values and parameters derived by the utility function F2 can vary. For example, in the illustrated '~
the utility function F2 reports ~- ~n~ng volumes to 21 ~5071 WO 96/40405 PCT/US96/07809 ~1 be ~ocessed, l~ -ininq processing times, and the _ ant collection volumes and rates.
Another utility function F3 calculates and l~ ' , based upon the platelet yield derived by the utility function !F1, the optimal storage p L ' ~8 for the platelets in terms of the number of storage containers and the volume amount of PPP
storage media to use.
Other utility fllnr~i~n~ generate control variables based upon ong~Ding proc~inq conditions for use by the applications control manager 46 to establish and maintalin optimal processing conditions. For example, one utility function F4 generates control variables to optimize platelet separation conditions in lhe first stage 24. Another utility function F5 generates control variables to control the rate at which citrate anticoagulant is returned with the PPP to the donor to avoid potential citrate toxicit:y r~rtion~.
Yet another utility function F6 derives an estimated y-oceduLe time, which predicts the collection time before the donor is c~nn~cted.
Further details of these utility functions F1 to F6 will now be desaribed in greater detail.
III. D~rivlnq P:L~t-lot Yi-ld The utility func:tion Fl (see Fig. 4) makes continuous calculations of the platelet separation efficiency (np~t) of the system 10. The utility function Fl treats the platelet separation efficiency ~Ptl as being the same as the ratio of plasma volume separated from the donor's whole blood relative to the total pla~sma volume available in the whole blood. The utility function Fl thereby assumes that every platelet in the pla~ma volume separated ~rom the donor's whole blood will be harvested.

~ Wos6/4040~ 12 1 9 5 G 7 1 PCT~S96/07809 The donor's hematocrit changes due to t~coA~ll~nt dilution and plasma depletion effects during procP~ng, so the separation efficiency np~t does not remain at a constant value, but changes throughout the ~ocedu~. The utility function Fl contends with these pL 0~55 ~p~nd~nt changes by monitoring yields in~L~ Lally. These yields, called in~L~ Lal cleared volumes (~ClrVol), are calculated by multiplying the current separation efficiency ~PIt by the current in~L -rLal volume of donor whole blood, diluted with an~1cnAq~lAnt, being pL~cessed, as follows:
Eg (1) ~ClrVol =ACDilxnp,tK~VOLproc where:
~ Volp~ i8 the in~L- L~l whole blood volume being ploce3sed, and ACDil is an anticoagulant dilution factor for the in~L~ L~l whole blood volume, computed as follows:
~q ~2 ACDil=
AC+ 1 where:
AC is the selected ratio of whole blood volume to anticoagulant volume (for example lO:l or ~lO"). 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 proc~lnq period.
For example, AC can be set at the outset of proc~s;nq at a lesser ratio for a set initial period of time, and then increased in steps after ~ u .~ time periods; ior 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 ~L e3~UL e of PRP
entering the second processing stage 32. For example, AC can be set ,at 6:1 until the initial ~La~DuLG (e.g. at 500 mmHg~ falls to a set threshold level (e.g., 200 mmHg to 300 mmMg). AC can then be raised in steps up to the processing level of 10:1, while monitoring the pI~~uL~ to assure it remains at the desired level.
The utility rlmction F1 also makes continuous estimates oE the donor's current circulating platelet count (PltC~rc), e~ ed in terms oiE 1000 platelets per microliter (~l) of plasma volume (or k/~l). Like np~t, Pltclrc will change during proc~sing due to the effects Or dilution and depletion. The utility Eunction Fl ir~L~ ally monitors the platelet yield in in~ 5, too, by multiplying each in~L. Ldl cleared plasma volume ~ClrVol (based upon an in~,tantaneous calculation of np~t) by an instantaneous estimation of the circulating platelet count Pltcl,. The product is an ih~L~ --tal platelet yield (ayld), typically ~L,ssed as e" platelets, where "e ~ .5 x 10 platelets (e11 = .5 x 1011 platelets).
At any given time, the sum of the in~L. L~l platelet yie:Lds ~Yld constitutes the current platelet yield YldCurr,nt~ which can also be ~yL~ .' as follows:

~ WO 96140405 19 PCT/US96/07809 Eq ~3) ~ClrVol x Pl t Yldcurr~nt= YldOldl 100~ 000 where:
Yldold is the last calculated YldCu,,~nt, and Eq ~4) ~ClrVol x Pl tCurr n Yl d= t 100,000 where:
Pltcu,,,nt is the current (instantaneous) estimate of the circulating platelet count Or the donor.
~Yld is divided by 100,000 in Eq (4) to balance units.
The following provides further details in the derivation of the above-described procP~ing variables by the utility function F1.
. D-riving Ov-rall 8-paration ll!ffi~ J llVlt The overall system efficiency nplt is the product of the individual efficiencies of the parts Or the system, as ~ ~ssed as follows:
Eq ~5) nplt=nl,tS~pXn2ndS~PXI~ ln~
where:
n"t~p is the efficiency of the separation of PRP from WB in the first separation stage.
n2n~ is the efficiency Or separation PC
from PRP in the second separation staqe.
nAn, is the product of the efflr~ iP~ of other An~illA~y procesClng steps in the system.
1. First 8tag- 8~"~ _ti~r W096i40405 PCT~S96/07809 Ef~ci~noy n1.tseP
The utility function F1 (see Fig. 4~
derives n~,t5ep continuously over the course of a pI~ced~ e based upon measured and empirical processing values, using the following expression:
Eig (6) rl = QP
( l--Hb) Qb where:
Qb is the -~~ e~d whole blood flow rate (in ml/min).
Qp is the ---- ed PRP flow rate tin ml/min).
Hb i5 the apparent hematocrit of the Anti~o~ulated whole blood entering the first stage separation ~ ~ ; L. Hb is a value derived by the utility based upon sensed flow conditions and theoretical consideratiom3. The utility function Fl there~ore requires no on--line hematocrit sensor to measure actual WB hematocrit.
The utility function Fl derives Hb based upon the rollowing relatj on~h i r ~g ~7) ,~ = Hrbc( Qb Qp) Qb where:
H,b, il3 the apparent hematocrit o~ 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 Hb, the utility function F1 requires no physical sensor to determine H,b" which i8 derived by the utility function according to the following 2 1 9507 ~

~ W O 96/40405 ~ 2 1 ~ PCT~US96/07809 expression ~g ~8) rbc ( gAKS ( qb ~p) ) where qb is inlet blood flow rate (cm3/sec), which is a known quantity which, when converted to ml/min, CVLL~ ~,o~ds with Qb in Eq (6) .
$ is measured PRP flow rate (in cm3/sec), which is a known quantity which, when ~On~eL ted to ml/min CC L L ~,,~unds with Qp in Eq (6) .
~is a shear rate ~ ,t term, and sy is the red blood cell ~e~i tation coefficient (sec) Based upon empirical data, Eq (8) assumes that ~/Sy=15 8x106 sec1 A is the area of the separation chamber (cmZ), which is a known ~ n.
g is the centr$fugal acceleration (cm/sec2), which is the radius of the first separation chamber (a known dimension) multiplied by the rate o~
rotation squared n2 (rad/s~c) (another known quantity) k is a viscosity vvlD~In~ -- 0.625~ and }c is a viscosity cvn~t~llt based upon k and another viscosity cvl.tarlt ~ ~ 4 5~ where Eq ~9) lc+2 k+2 ~1 ~ ~ [ k+l] 1 272 Eq (8) is derived rrom the rela~ ah lp8 e~ _ssed in the following Eq (10) W096/40405 - 22 - PCT~S96/0~809 ~g ~10) Hrbc(1~Hrbc)~ l~= A-set forth in Brown, The PhVsics of Con~;n1~us Flow Centr.ifuqal Cell Se~aration, "Artieicial Organs" 198'3; 13(1):4-20)). Eq (8) solves Eq (10) for Hr~.
2. I'ho 8-cond 8tag- 8eparation E~ffiaienaY n~p The utility func:tion F1 (see Fig. 4) also derives nzr~ continuously over the course of a p~oceduLe based upon an algorithm, derived from computer --'~li ng, that calculates what fraction of lo~ n~L~,ally 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 (Qp), area (A) of thle separation stage 32, and centrifugal acceleration (g, which is the spin radius of the second stage multiplied by the rate of rotation squared nZ).
The algorithm can be e~ 33ed in terms of a function shown gr~ph;c~lly in Fig.8. The graph plots n~ p in terms O:e a single dimensionless parameter gASp/Qp, where:
Sp = 1.8 X 109 MPY2n (sec), and MPV is the mean platelet volume~5 (femtoliters, fl, or cubic microns), which can be ed by conv~nt;~n~l techniques from a sample of the donor's blood collec1cd before procC~e;ng. There can be variations in MPV due to use of different counters. The utility function U._-ef~-~ may include a look up table to standardize MPV for use by the function according to tlhe type of counter used.

21 9~07~
~ PCT~Sg6/07809 _ w096/4040s - 23 -Alternatively, MPV can be estimated based upon a function derived from statistical evaluation Or clinical platelet pL~u~nt Pltp~E data, which the utility function can use. The inventor believes, based upon his evaluation of such clin;cAl data, that the MPV function can be e~Lessed as:
MPV (fl) # 11.5 - o.oO9PltppE (kt~l) 3. Ancillary 8-paration ll!ff~ nAnc nAnc takes into account the efficiency (in terms of platelet loss) of other portions of the processing system. ~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 L', ~ nQi~ . and transferral of platelets (in PC) from the second stage chamber after procP~~inq; and the Pffic~en~y of ~e~u~e3~ing previously pIucessed blood in either a single needle or a double needle configuration.
The eff1~;Pn~;pQ of these ancillary process steps can be AQsP~-ed based upon clinical data or estimated based upon computer - '-l;nq. Based upon these c-n-id-rations, a predicted value for ~Anc can be -QsiqnD~ which Eq (5) treats as constant over the course of a given p~ocL_uLe.
B. D-riving Donor Plat-let Count ~PltC~") The utility function Fl (see Fig. 4)relies upon a kinetic model to predict the donor's current circulating platelet count PltCi,c during proc-,Qinq.
The model estimates the donor's blood volume, and then estimates the efrects of ~ n and depletion during prO-PsQ;nq, to derive Pltci,c, according to the 2 ~ '~507 1 w096/40405 - 24 - PCT~596/0780s -~ollowing relationships:
Bg ~11) Plt Clrc~[ ~ Diluti on)x Pltpr.] -~Depleti on) where:
Pltp,e i8 the donor's circulatinq platelet count before proce~lng begins (k/~l), which can be - ed by conventional terhni-~u~ from a sample of whole blood taken from th,e donor before proc~c~ing.
There can be variations in Pltp,r due to use of different counters (see, e.g., Peoples et al., ~A
Nulti-Site Study of Variables Affecting Platelet Counting for Blood r ~1t 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, Pltp,e ancl Pltpost, described later) ~or use by the function according to the type of counter used.
Dil ution is a factor that reduces the donor's ~ roc~inq circulating platelet count Pltp,. due to increases in the donor's apparent circulating blood volume caused by the priming volume of the system and the delivery of ~n~icoAr~ nt. Dilution al80 takes into account the ~nt;n--r~llR removal of fluid from the vascular space by the kidneys during the ~LoceduL~.
Depletion i8 a factor that takes into account the depletion of the donor's available circulating platelet pool by processing. Depletinn also takes into account the counter ~ iz~tion of the spleen in restoring platelets into the circulating blood volume during proC~ ing.
1. El~ t~n'J Dllution 2~ ~5071 -- I'CT/US96/07809 The utility function Fl estimates the dilution factor based upon the following expression:
Eg 112) Prime+ 2ACD ppp Dil ution=1- 3 DonVol where:
Prime is the priming volume of the system (ml)-~ CD is the volume of anticoagulant used(current or end-point, ~pen~ing upon the time the derivation is made~tml).
PPPis the volume of PPP ~ollect~ (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 15 against donor weight linearized through regression to the following, more str~mlin~ expre5sion:
~ Xg (13~
DonVol=1024 l51Wgt(r2=0.87) where:
Wgt is the donor's weight (kg).
2. Estimating r~rret~
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), e~ ad as rollows:

W O 96/40405 - 26 - P~rAD596/07809 I~q ~

Depl 10 0, OOo Yld DonVol where:
Yld is the current instantaneous or goal platelet yield (k/~l). In Eq ~14), Yld is multiplied by lOO,oO0 to balance units.
Eq (14) does not take into account splenic mobilization of repl~c L platelets, which is called the splenic ~ ation factor ( or Spleen).
Spleen indicates that donors with low platelets counts nevertheless have a large platelet reserve held in the spleen. During procD~sing, as circulating platelets are withdrawn from the donor's blood, the spleen releal~es platelets it holds in reserve into the blood, thereby partially offsetting the drop in circulating p:Latelets. The inventor has dis~uv~led that, even though platelet ~.ecuu.,Ls vary over a wide range among donors, the total available platelet volume remains remarkably con~tant 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 norma]L donors.
The inventor has derived the 'il;7Dtion factor Spleen from comparing actual measured depletion to Depl (Eq (]4)), which is plotted and linearized as a function of Pltpr,. Spleen (which is restricted to a lower limit of 1) is set forth as follows:
Eg ~15) Spleen=[2.25-0.004Pltpr~] ~1 2 ~ 9~07 1 W096i4040s - 27 - PCT~sg6/0780s Based upon Egs (14) and tl5), the utility function derives Depletion as follows:
~q ~16) . 100,000 Yld Depletlon=
Spl een xDonVol C. ~eal Time P,.
~oaification~
The v~_~atu~ will not always have a current platelet pL~ cuu~ Pltp" for every donor at the heg;nning of the pLvcedure. The utility function Fl allows the system to launch under de~ault parameters, or values from a previous ~Lucedu~e.
The utility function Fl allows the actual platelet pLC UUIlL Pltp", to be entered by the vp_L~oI later during the ~Locedu.e. The utility function Fl recalculates platelet yields detPrminPd 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 ~r. cvu..~ d~,e~ n~
nature of splenic ';1;7~tion.
The utility function Fl uses the current yield to calculate an effective cleared volume as ~ollows:
(17) lOO,OOOxDonVolx Yld ClrVo~ C~r:~nt ACD ppp 50,000XYld [DonVol-Prime- + ] xPre - SpleenOId where:
ClrVol is the cleared plasma volume.
DonVol is the donor's circulating blood volume, calculated according to Eq (13).

21 ~5071 .

Yldcu",nt is the current platelet yield calculated according to Eq (3) based upon current proceC,C, inq conditions.
Prime i6 the blood-side priming volume (ml).
ACD is the volume of anticoagulant used (ml).
PPP is the volume of platelet-poor plasma collected (ml).
PreOId is the donor's platelet count before processing entered before processing begun (kt~l).
SpleenOId is the !iplenic ~ ;7~tion factor calculated using Eq (16) based upon PreOld.
The utility function Fl uses ClrVol calculated using Eq (17) to calculate the new current yield as follows:
Eq (18~
DonVol-Prime- 3 ~ 2ClrVolxPreb~w ]
N~w Donvol+ Clrvol 100, 000 2x Spl ,eenN~W

where:
PreN,~ is the revised donor platelet pre-count entered during proc~s; nq (k/~l) .
Yldu,f is the new platelet yield that takes into account the revised donor platelet ~ uu PreN~.
ClrVol is the cleared plasma volume, calculated according to ]3q (17).
DonVol is the donor's circulating blood volume, calculated accorcling 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 Eg (17).
PPP is the volume of platelet-poor plasma collected (ml), same as in Eg (17).
cple~ is the splenic ';l;7~tion factor calculated using Eq (15) based upon Pre~.
lV. Der~vinq otb-r Proc~ Tnformation The utility function F2 (see Fig. 5) relies upon the calculation of Yld by the first utility function Fl to derive other informational values and parameters to aid the operator in determining the optimum operating conditions for the pL0~6dULe. ~he follow proces5ing values exemplify derivations that the utility function F2 can provide.
A. r inl~~ VolU~Q to b- P ~5~d The utility function F2 calculates the additional pLoces~ed volume needed to achieve a desired platelet yield Vbr_ (in ml) by dividing the re~~; n; ng yield to be collected by the expected average platelet count over the ~. ;n~- of the ~' Oc6du~e~ with corrections to reflect the current operating efficiency nplt. The utility function F2 derives this value using the following expression:
~q ~19) 200~000X( Yld~ ~Yldcur~t) rlpltxACDilx (PltCur~wt+Pltpo t) where:
YldG~I is the desired platelet yield (k/~l), where:
Vbr~ is the additional proc~;ng volume (ml) needed to achieve YldGo~l Yld~"~t is the current platelet yield (k/~l), calculated ur~ing Eq (3) based upon current prore~in~ values.

21 9507l PCT~S9~07809 -W09~4040~ - 30 -nplt is the present (in~AntAnPol~C) platelet collD~ti~n efficiency, caLculated using Eq (5) based upon current procp~cing values.
ACDil is the anticoagulant dilution factor (Eq (2)).
PltCu,rnt is the current (instantaneous) circulating donor platel,et count, calculated using Eq (11) based upon current procDqc;ng values.
Pltp~t i8 the ~ected donor platelet count lo after pro~Dcsing, also calculated using Eq (11) based upon total processing values.
B. r ~ P~ . Time The utility function F2 also calculates ,~ ;n;ng collect;on time (t,~) (in min) as follows:
Eq (20 _ V~r lc t ~---where:
Vb,~ is the ~. ;n;ng volume to be pI ocessed, calculated using Eq (19) based upon current processing conditions.
Qb is the whole blood flow rate, which is either set by the user or calculated as Qb~t using Eq (31), as will be described later.
C. Plasmil Collection The utility fwlction F2 adds the various plasma collection requirements to derive the plasma 25 collection volume (PPP~L) (in ml) ac follows:
Eg ~21) PPPGO-I PPPPC PPPSOUrCe P~?PR~fnfUI~I PPPanSt~t PPPCOI1Cb~r~
where:
PPPpC is the pLatelet-poor plasma volume ~elec~Dd for the PC product, which can have a 21 ~5071 ~ W09614040s 31 PCT~Sg6/07809 , . . .
typical default value of 250 ml, or be calculated as an optimal value Plt~ according to Eq (28), as will be described later.
PPPsourc~ i5 the platelet-poor plasma volume selected for co-lect~on as source plasma.
PPP~..t. is the platelet-poor plasma volume selected to be held in reserve for various processing ~uL~oses (Default - 30 ml).
PPPCol~ch~ is the volume of the plasma collection chamber (Default - 40 ml).
PPPReInfU~ is the platelet-poor plasma volume that will be reinfusion during processing.
D. ~la~ma Coll-ction Rat-The utility function F2 calculates the plasma colle~ n rate (Qhw) (in ml/min) as follows:
Eq (22) PPP -PPP
Qpp = Go~l Currene ren where:
PPP~o~l i8 the desired platelet-poor plasmA
collection volume (ml).
PPP~"~t is the current volume of platelet-poor plasma collected (ml).
tr~ is the time r~ in~nq in collection, calculated u6ing Eq (20) based upon current processing conditions.
E. Tot~l ~t~o~p~t-d AC U8ag-The utility function F2 can also calculate the total volume of anfi~oa~l~nt e~ecLed to be used during proc~s;ng (ACD~) (in ml) as follows:
~q ~23) ACD~nd~ACDcl rr ne 1 ~:AC

21 5~071 w096/40405 - 32 - PCT~S96/07809 where:
ACDCurr~ i5 the current volume of anticoagulant used (ml).
AC is the seleclted anticoagulant ratio, Qb is the whole blood flow rate, which i8 either set by the user or calculated using Eq ~31) as Qb~t based upon current processing conditions.
t,~ is the time ~- ining in collection, calculated using Eq l~20) based upon current processing conditions.
V. ~ç~Qmendirw ODtimum Pl~Ltelet ~tor~Lcre P~ ~s The utility function F3 (see Fig. 6) relies upon the calculation of Yld by the utility function Fl to aid the operator in determining the optimum storage conditions for the platelets collected during proc~ n7.
The utility function F3 derive5 the optimum ~torage conditions to sustain the platelets during the expected storage period in terms of the number of preselected storage containers requLired for the platelets Plt~ and the volume of plasma (PPP) Plt~
(in ml) to reside as a storage medium with the platelets.
The optimal storage conditions for platelets depends upon the volume being stored Pltvol, e~Lessed as follows:
~g (2~) Pl tvol= YldXMPV

where:
Yld is the number of platelets collected, and NPV is the mean platelet volume.
As PltVol increases, 50 too does the ~ WO 96/40405 _ 33 _ PCT/US96/0~809 platelets' demand for oxygen during the storage period. As Pltvol increases, the platelet5' glucose _ tion to support metabolism and the generation of carbon dioxide and _actate as a result of metabolism also increase. The physical characteristics of the storage containers in terms of surface area, 1hi~n~Rs, and material are selected to provide a desired degree of gas permeability to allow oxygen to enter and carbon dioxide to escape the container during the storage period.
The plasma storage medium contains hiC~ te HC03, which buffers the lactate ~ L~ted by platelet metabolism, keeping the pH at a level to sustain platelet viability. As PltVol increases, the demand for the buffer effect of HC0~, and thus more plasma volume during storage, also increases.
A. Deriving Plt~
The partial ~~~uL~ of oxygen P~2 (mmHg) of platelets stored within a storage contli nar having a given permeation decreases in relation to the total platelet volume PltVol the container holds.
Fig. 9 is a graph based upon test data showing the relati~n~hip between P02 measured after one day of storage for a storage c~n~i n~r of given permeation.
The storage cnn~ i n~ upon which Fig. 9 is based has a surface area of 54.458 in2 and a capacity of 1000 ml. The storage container has a p~L - -h; 1; ty to ~2 of 194 cc/100 in2/day, and a F~ -h; 7 ity to C02 1282 CC/100 in2/daY.
When the partial ~ es_~L~ P02 drops below 20 mmHg, platelets are obs_~ l to become anaerobic, and the volume of lactate L~LOd~L increases significantly. Fig. 9 shows that the selecte~
storage container can maintain pOz of ~0 mmHg (well 21 9507~ -above the aerobic region) at PltVo~ S 4 . O ml. On this conservative basi~, the 4.0 ml volume i8 selected as the target: volume PltTvol for this container. Target volumes PltTvol for other ~o~t~in~rs can be determined using this same methodology.
The utility function F3 uses the target platelet volume PltTvol to compute PltB.9 as follows:
Eq (25) Plt ~Vol and:
Plt8.9 = 1 when BAG S 1.0, otherwise PltB.9 = [BP.G + 1], where tBAG + 1] is the integer part of the quantity BAG + 1.
For example, given a donor MPV Or 9.5 fl, and a Yld of 4 x 1011 platelets (Pltvol = 3 . 8 ml), and given PltTvol = 4.0 ml, BAG ~ 0.95, and Plt8.9 = 1. If the donor MPV is 11.0 fliand the yield Yld and PltTvol remain the same (Pltvol = 4.4 ml), BAG - 1.1 and PltB.9 2.
When PltB.9 > 1, Pl~l is divided equally among the number of containers called for.
2. DerivLng Plt~
The amount of bi~LL~..ate used each day i8 a function of the storage tl.L -_y~ocrit Tct (~), which can be ~ ssed as follows:
Eg ~26 Pl t vo~
Pl t~,d The relati~n~h;r between bic~LLu..ate HCO~
c~ ion per day and Tct can be empirically d~t~rmln~ for the select:ed storage container. Fig.
10 shows a graph showing this relati~n~hlr for the 2t 95071 ~ WO 96/40405 _ 35 _ PCTIUS96/07809 same container that the graph in Fig. 9 is based upon. The y-axis in Fig. 10 shows the empirically measured ~: _tion of bicarbonate per day (in Meq/L) based upon Tct for that container. The utility function F3 includes the data eA~ d in Fig. lO in a look-up table.
The utility function F3 derives the anticipated decay of bicarbonate per day ove~ the storage period ~HC03 as rollows:
Eq ~27) ~Co = ~~~
3 Stor where:
DonH~3 is the measured bicarbonate level in the donor's blood (Meq/L)~ or alternatively, iB the bicarbonate level for a typical donor, which is believed to be 19.0 Meq/L +
1.3, and Stor i5 the desired storage interval (in days, typically between 3 to 6 days).
Given ~HC03, the utility function F3 derives Tct from the look up table ~or selected storage container. For the storage container upon which Fig.
10 i8 based, a Tct of about 1.35 to 1.5% i8 believed to be c~ r~tively a~ iate in most instances for a ~ix day storage interval.
Knowing Tct and PltVol, the utility function F3 ~_ _Les Plt~ based upon Eq (25), a8 follows:
Eg (28) Plt ~d Tct .

When PltB.~ > 1, Pl~ is divided equally .~

2l ~5Q71 W O 96/40405 - 36 - PC~r~US96/07809 among the number oi cont:ainers called for. PPPpc is set to Plt~ in Eq (21).
VI. Dcrivinc~ Con~rol V~ri~h~
The utility fun,ctionfi F4 and F5 rely upon the above-described matrix of physical and physiological relat;on~:h;rs to derive proce6s control variables, which the application control manager 46 uses to optimize system performance. T~e iFollow control variables exemplify derivations that the utility i~l~nr~;~n~ F4 and F5 can provide for this purpose.
A. Promoting ~igh Platelet 8-paration ~i~rici~ By ~-circulation A high mean platelet valueMPV for collected platelets is desirable, as it denotes a high separation ei~ficiency for the iEirst separation 6tage and the system overall. Most platelets average about 8 to 10 femtoliters, as measured by the Sysmex K-lOoo machine (the smallest of red blood cells begin at about 30 iEemtoliters). The ~. lninq minority oi~ the platelet population constitutes platelets that are physically larger. These larger platelets typically occulpy over 15 x 10l5 liter per platelet, and some are larger than 30 femtoliters.
These larger platelets settle upon the ~3C
interface in the first separation chamber quicker than most platelets. These larger platelets are most likely to become ~,-LL~ed in the ~3C interi~ace 3 0 and not enter the PRP iEor collection. EfiEicient separation of platelets in the iEirst separation chamber lifts the larger platelets from the ~ Lrace for collection in the P~P. This, in turn, results a greater populal:ion oiE larger platelets in the PRP, and therefore a higher MPV.

21 9507l ~ WO 96/4040S PCI/13S96/07809 Fig. 11, derived from clinicAl data, shows that the efficiency of platelet separation, ~ ed in terms of MPV, is highly d~r~ nt upon the inlet hematocrit of ~3 entering the first stage processing chamber. This is ~cpQclAlly true at hematocrits of 30% and below, where significant lncreases in separation efficiencies can be obtained.
Ba8ed upon this consideration, the utility function F4 sets a rate for recirculating PRP back to the inlet of the first separation stage QR~ e to achieve a desired inlet ~ -to~ lt Hl selected to achieve a high MPV. ~he utility function F4 selects H~ based upon the following red cell balance equation:
~g (29) QR circ= [ H 1 ] Qb In a preferred 1 l~ Lation, Hl is no greater that about 40~, and, most preferably, is about 32%.
B. Citrate Infusion Rate Citrate in the an~iCoAgul~nt is rapidly metabolized by the body, thus allowing its continuous infusion in ~tLuL..cd PPP during proc~ccing. However, at some level o~ citrate infusion, donors will experience citrate toxicity.
These reArti~n~ vary in both ~LL_n~Lh and nature, and different donors have di~ferent threshold levels. A nominal a-symptomatic citrate infusion rate (CIR), based upon empirical data, is believed to about 1.25 mg/kg/min. This is based upon empirical data that shows virtually all donor~ can tolerate apheresis comfortably at an antico~, lated 21 q5071 WO 96/40405 ~ 3 8 -- PCT/US96/07809 blood flow rates of 45 m~/min with an anticoagulant (ACD-A anticoagulant) ral:io of 10:1.
Taking into account that citrate does not enter the red cells, the amount given to the donor can be reduced by continuously collecting some fraction of the plasma throughout the ~LoceduL~, which the system accomp:Lishes. By doing so, the donor can be run at a higher flow rate than wou;Ld be ~Yp~ct~A otherwise. l'he maximum a ~y ~ tic equivalent blood flow rate (EqQbcl~) (in ml/min) under these conditions i!; believed to be:
~g (30) ~qQbc~R= C t~ C 1) Wgt where:
CIR is the selected nominal a LY, t LiC
citrate infusion rate, or 1.25 mg/kg/min.
AC is the selectsd antiCoagul~nt ratio, or 10:1.
Wgt is the donor's weight (kg).
CitrateConc is the citrate cu...c..LL~tion in the ~Pl~rt~ antiCoAgl~lAnt~ which is 21.4 mg/ml for ACD-A an~icoaglll~nt.
C. Opt~m~ Anticoagulat-d Blood Flow The L~ ining volume of plasma t3hat will be ICLUL~Ied to the donor is equal to the total amount availa3ble reduced by the amount ~till to be collected. This ratio is used by the utility function F5 (see Fig. 5) to ~et~rmin~ the maximum, or optimum, a-symptomatic blood flow rate (Qb~t) (in ml/min) that can be drawn from the donor, as follows:

21 95~71 ~ WO 96/40405 3 9 PCT/US96/07809 E~I~31) ( 1- FIb ) X Vb where:
Hb is the anticoagulated hematocrit, calculated using Eq (7) based upon current processing conditions.
Vb~ is the ~ in;nq volume to be pLo~essed, calculated using Eq (19) based upon current processing conditions.
EqQsclR is the citrate equivalent blood flow rate, calculated using Eq (30~ based upon current 10 processing conditions.
PPPco,l is the total plasma volume to be collected tml).
PPPCU"~t is the current plasma volume collected (ml).
~II. ~-t~r-t~ ~L-~r~ -. T~--The utility function F6 (see Fig. 7) derives an estimated pro~6JuL~ time (t)(in min)~
which predicts the collection time before the donor is connected. To derive the estimated ~rOcedu-~
time t, the utility function F6 requires theoperator to input the desired yield YldCo.~ and desired plasma co~ on volume PPPGO~I~ and further requires the donor weight Wgt, platelet ~r_ ~OUIIL
Plt~,., and hematocrit Hb or a default estimate of it.
If the operator wants I. '~I platelet storage par ~, the utility function requires MPV as an input.
The utility function F6 derives the estimated pLOCedULe time t as follows:

21 95071 ~ ~
W O 96/40405 PC~r~US96/07809 Eq (32) ~ -b~

where:
Eg (33) H -.N
a= (; Jl ) EqQb crR

Eg ~34) b= (Neq Hb AHb qQ Cl~ ~X~qPV

Eg (35) (1 Hb) (1 ~) and where:
H~q iB a lineari.zed expression o~ the RBC
hematocrit H~8C, as follow8:
Eq ~36) H q=O. 9489-AHbE~QbcrR

where:
Hb is the donor's anticoagulated hematocrit, actual or del'ault estimation.
EqQbc~ is the mnximum a ~ ,t tic eguivalent blood flow rate calculated according to Ec~ t30).
and Eg (37) =61~463 _ W096/4040s - 41 -- where:
Q i8 the rotation speed of the ~ processing chamber (rpm).
and where:
PPP i5 the desired volume o~ plasma to be collected (ml~.
PV is the partial proces~ed volume, which is that volume that would need to be processed if the overall separation efficiency nplt was 100$, derived as follows:
~q ~38 PV ClrVol n.,~,c x~ 2 ~,dS,,pX ACDi 1 where:
ACDil is the anticoagulant dilution factor (Eq (2)).
ClrVol is the cleared volume, derived aE~:
Eq ~39) 100, OOOxDonVol Xyld ~lrVol=
tDonVol-Prime~ t+ PPP] xplt 50, oOOxYlc where:
Yld is the desired platelet yield.
DonVol is the donor's blood volume - 1024 + 51Wgt (ml).
Prime is the blood side priming volume of the system (ml).
ACDE,t is the estimated A~t;~oagulant volume to be used (ml).
Pltpr. ls the donor's platelet count before processing, or a default estimation of it.
Spleen is the i~ the splenic r~ tion ~actor calculated using Eq (16) based upon Pltp,..

The function F6 also derives the volume of whole blood needed to be y~ces1Ld to obtain the desired Yldco.l. This procP~sing volume, WBVol, i8 e~yL~ssed as follows:

Wpvol = t X EqQbc~n X (1 _ N ) ~ WBn~s where:
t is the estimated y cedu.e time derived according to Eq(:32).
Hb is the donor's anticoagulated hematocrit, actual or default estimation.
EqQbc~R is the maximum a-symptomatic equivalent blood flow rate calculated according to Eq (30).
PPPc~L is the desired plasma c~llPc~n volume.
WBREs is the residual volume of whole blood left in the system after procP~sing, which is a known system variable and depends upon the priming volume of the system.
Various feature~i of the inventions are set forth in the following claims.

Claims

I claim:

1. A system for recommending storage parameters for a blood component comprising an input to receive selected storage criteria information, and a processor coupled to the input to generate as output, based upon the selected storage criteria information, recommended storage parameters comprising a recommended number of selected storage containers to be used and a recommended volume of storage medium to be used.

2. A system for recommending storage parameters for a prescribed number of platelets in a prescribed gas permeable container and in association with a specified storage medium including an input to receive selected storage criteria information, and a processor coupled to the input to generate as output, based upon the selected storage criteria information, recommended storage parameters comprising a recommended number of selected storage containers (PltBAG) to be used and a recommended volume of storage medium (PltMED) to be used.

3. A system according to claim 2 wherein the selected storage criteria information that the input receives includes a value representing number of platelets to be stored (Yld) and a value representing measured mean platelet volume of the platelets to be stored (MPV)(in fl), and wherein the processor calculates a platelet volume (PltVOL) as follows:
PltVOL=Yld x MPV

4. A system according to claim 3 wherein the selected storage criteria information that the input receives includes a targeted platelet volume for the selected container (PltVOL) (in ml), taking into account the gas permeability of the selected container, and wherein the processor derives a number value BAG:

and wherein PltBAG = 1 when BAG ~ 1, otherwise PltBAG
= [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1].

5. A system according to claim 3 wherein the selected storage criteria information that the input receives includes a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and wherein the processor derives PltMED (in ml) as follows:

6. A device for recommending storage parameters for a prescribed number of platelets having a measured mean platelet volume in a prescribed gas permeable container and in association with a specified storage medium, the device comprising:
an input to receive storage criteria information comprising a value representing the number of platelets to be stored (Yld), a value representing the measured mean platelet volume of the platelets to be stored (MPV) (in fl), a targeted platelet volume for the selected container (PltTVOL) (in ml), taking into account the gas permeability of the selected container, and a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and a processor coupled to the input that generates, based upon the inputted values, a recommended storage parameter output comprising a value representing the number of selected storage containers to be used (PltBAG) and a value representing the recommended volume of storage medium PltMED for the platelets, where the volume of platelet to be stored (PltVOL) (in ml) is:
PltVOL=Yld X MPV
where a number value BAG is:

where PltBAG = 1 when BAG ~ 1, otherwise PltBAG = [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1], and where PtlMED (in ml) is:

7. A device according to claim 6 wherein the selected storage medium contains bicarbonate, and wherein the input receives the targeted platelet volume based, at least in part, upon maintaining a partial pressure of oxygen of platelets above a set aerobic region when stored in the storage medium in the selected storage container.

8. A device according to claim 7 wherein the selected storage medium comprises plasma.

9. A system for collecting platelets for storage comprising a separation device that separates blood into plasma and platelets an inlet to the separation device for conveying anticoagulated blood containing plasma and platelets from a donor into the separation device for separating into a plasma yield and a platelet yield, a first outlet to the separation device to returning at least a portion of the yield of plasma to the donor while collecting at least a portion of the yield of platelets for storage in a selected gas permeable storage container in association with a selected storage medium, a processing element coupled to the separation device including an input to receive storage criteria information comprising a value representing the portion of the yield of platelets to be stored (Yld), a value representing a measured mean platelet volume of the platelets to be stored (MPV)(in fl), a targeted platelet volume for the selected container (PltTVOL) (in ml), taking into account the gas permeability of the selected container, and a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and the processor further including an element coupled to the input that generates, based upon the inputted values, a recommended storage parameter output comprising a value representing the number of selected storage containers to be used (PltBAG) and a value representing the recommended volume of storage medium PltMED for the platelets, where the volume of platelet to be stored (PltVOL) (in ml) is:
PltVOL = Yld x MPV

where a number value BAG is:

where PltBAG = 1 when BAG ~ 1, otherwise PltBAG = [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1], and where PtlMED (in ml) is:

10. A system for collecting platelets for storage comprising a separation device that separates blood into plasma and platelets an inlet to the separation device for conveying anticoagulated blood containing plasma and platelets from a donor into the separation device for separating into a plasma yield and a platelet yield, a first outlet to the separation device to returning at least a portion of the yield of plasma to the donor while collecting the yield of platelets for storage in a selected gas permeable storage container in association with a selected storage medium, a processing element coupled to the separation device including an element that derives, at least part while separation occurs in the separation device, the yield of platelets to be stored, an input to receive storage criteria information comprising the yield of platelets to be stored (Yld), a value representing a measured mean platelet volume of the platelets to be stored (MPV)(in fl), a targeted platelet volume for the selected container (PltTVOL) (in ml), taking into account the gas permeability of the selected container, and a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and an output coupled to the input to generate, based upon the inputted values, a recommended storage parameter output comprising a value representing the number of selected storage containers to be used (PltBAG) and a value representing the recommended volume of storage medium PltMED for the platelets, where the volume of platelet to be stored (PltVOL) (in ml) is:
PltVOL = Yld x MPV

where a number value BAG is:

where PltBAG = 1 when BAG ~ 1, otherwise PltBAG = [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1], and where PtlMED (in ml) is:

11. A system according to claim 10 wherein the element that determines the yield of platelets to be stored includes means for determining the incremental plasma yield during a succession of incremental time periods during the separation step, means for estimating a current count of circulating platelets available from the donor during each incremental time period, means for multiplying the determined incremental plasma volume for each incremental time period by the estimated current count of circulating platelets for each incremental time period, to derive an incremental platelet yield for each incremental time period, and means for summing the incremental platelet yields over the succession of incremental time periods to obtain the derived yield of platelets.

12. A method for recommending storage parameters for a blood component comprising inputting selected storage criteria information, and generating as output, based upon the selected storage criteria information, recommended storage parameters comprising a recommended number of selected storage containers to be used and a recommended volume of storage medium to be used

13. A method for recommending storage parameters for a prescribed number of platelets in a prescribed gas permeable container and in association with a specified storage medium including the steps of receiving as input selected storage criteria information, and generating as output, based upon the selected storage criteria information, recommended storage parameters comprising a recommended number of selected storage containers (PltBAG) to be used and a recommended volume of storage medium (PltMED) to be used

14. A method according to claim 13 wherein the step of receiving selected storage criteria information includes receiving a value representing number of platelets to be stored (Yld) and a value representing measured mean platelet volume of the platelets to be stored (MPV) (in fl), and wherein the step of generating the recommended storage parameters includes calculating a platelet volume (PltVOL) as follows:
PltVOL = Yld X MPV

15. A method according to claim 13 wherein the step of receiving selected storage criteria information includes receiving a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and wherein the step of generating the recommended storage parameters includes deriving PtlMED (in ml) as follows:

16. A method according to claim 13 wherein the step of receiving selected storage criteria information includes receiving a targeted platelet volume for the selected container (PltTVOL) (in ml), taking into account the gas permeability of the selected container, and wherein the step of generating the recommended storage parameters includes deriving a number value BAG:

and wherein P1tBAG = 1 when BAG ~ 1, otherwise P1tBAG
- [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1].

17. A method according to claim 16 wherein the step of receiving the selected storage criteria information includes receiving a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and wherein the step of generating the recommended storage parameters includes deriving Pt1MED (in m1) as follows:

18. A method for recommending storage parameters for a prescribed number of platelets having a measured mean platelet volume in a prescribed gas permeable container and in association with a specified storage medium, the method comprising the steps of:
receiving storage criteria information including a value representing the number of platelets to be stored (Y1d); a value representing the measured mean platelet volume of the platelets to be stored (MPV) (in f1); a targeted platelet volume for the selected container (P1tTVOL) (in m1), taking into account the gas permeability of the selected container; and a desired thrombocytocrit (Tct) (expressed as a percentage) for the platelets during storage, and generating, based upon the inputted values, a recommended storage parameter output comprising a value representing the number of selected storage containers to be used (PltBAG) and a value representing the recommended volume of storage medium (P1tMED) for the platelets, wherein the volume of platelet to be stored (P1tVOL) (in m1) is calculated as follows:
P1tVOL = Y1d X MPV

wherein a number value BAG is calculated as follows:

wherein P1tBAG = 1 when BAG ~ 1, otherwise P1tBAG = [BAG + 1], where [BAG + 1] is the integer part of the quantity [BAG + 1], and wherein Pt1MED (in m1) is calculated as follows:

19. A method according to claim 18 wherein the selected storage medium contains bicarbonate, and wherein the targeted platelet volume is based, at least in part, upon maintaining a partial pressure of oxygen of platelets above a set aerobic region when stored in the storage medium in the selected storage container.

20. A device according to claim 19 wherein the selected storage medium comprises plasma.