U.S. patent application number 09/797176 was filed with the patent office on 2001-07-19 for blood processing systems and methods using apparent hematocrit as a process control parameter.
This patent application is currently assigned to Baxter International Inc.. Invention is credited to Brown, Richard I..
Application Number | 20010008221 09/797176 |
Document ID | / |
Family ID | 23879065 |
Filed Date | 2001-07-19 |
United States Patent
Application |
20010008221 |
Kind Code |
A1 |
Brown, Richard I. |
July 19, 2001 |
Blood processing systems and methods using apparent hematocrit as a
process control parameter
Abstract
Blood processing systems and methods separate whole blood into
red blood cells and a plasma constituent within a rotating
centrifugal separation device. The systems and methods convey whole
blood into the separation device through an inlet path including a
pump operable at a prescribed rate. The systems and methods remove
plasma constituent from the separation device through an outlet
path including a pump operable at a prescribed rate. The systems
and methods derive a value H.sub.b representing an apparent
hematocrit of whole blood entering the separation device, where: 1
H b = H rbc ( Q b - Q p ) Q b and where H.sub.rbc is a value
relating to hematocrit of red blood cells in the separation device.
The systems and methods generate outputs and control commands
based, at least in part, upon H.sub.b.
Inventors: |
Brown, Richard I.;
(Northbrook, IL) |
Correspondence
Address: |
RYAN KROMHOLZ & MANION, S.C.
Post Office Box 26618
MILWAUKEE
WI
53226
US
|
Assignee: |
Baxter International Inc.
|
Family ID: |
23879065 |
Appl. No.: |
09/797176 |
Filed: |
March 2, 2001 |
Related U.S. Patent Documents
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Application
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Filing Date |
Patent Number |
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09797176 |
Mar 2, 2001 |
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09527148 |
Mar 16, 2000 |
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6207063 |
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09527148 |
Mar 16, 2000 |
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08960674 |
Oct 30, 1997 |
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6059979 |
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08960674 |
Oct 30, 1997 |
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08473316 |
Jun 7, 1995 |
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5730883 |
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Current U.S.
Class: |
210/739 ;
210/143; 210/512.1; 210/787; 210/85 |
Current CPC
Class: |
A61M 2202/0071 20130101;
A61M 2202/0092 20130101; B04B 5/0442 20130101; A61M 1/308 20140204;
B01D 17/0217 20130101; A61M 2202/0092 20130101; A61M 1/30 20130101;
A61M 2202/0427 20130101; A61M 1/385 20130101; A61M 1/3624 20130101;
A61M 1/302 20140204; A61M 1/3603 20140204; B04B 7/08 20130101; A61M
2202/0415 20130101; A61M 1/3696 20140204; B01D 2221/10 20130101;
A61M 1/025 20130101; B01D 21/262 20130101; A61M 1/3672 20130101;
A61M 2202/0427 20130101; A61M 2202/0427 20130101; A61M 2205/331
20130101; A61M 1/0218 20140204; A61M 2205/3393 20130101; A61M
2205/3351 20130101; B01D 21/34 20130101; B04B 13/00 20130101; A61M
2202/0415 20130101; A61M 1/3693 20130101; A61M 1/303 20140204; B01D
21/2405 20130101; A61M 1/0209 20130101; B01D 21/26 20130101; A61M
2205/3355 20130101; B01D 21/245 20130101; A61M 2205/3344
20130101 |
Class at
Publication: |
210/739 ; 210/85;
210/143; 210/512.1; 210/787 |
International
Class: |
B01D 017/12 |
Claims
I claim:
1. A blood processing system comprising a centrifugal separation
device rotatable at a prescribed rate of rotation, an inlet path
including a pump operable at a prescribed rate Q.sub.b to convey
whole blood into the separation device for separation into red
blood cells and a plasma constituent, an outlet path including a
pump operable at a prescribed rate Q.sub.p to remove plasma
constituent from the separation device, an element to derive a
value H.sub.b representing an apparent hematocrit of whole blood
entering the separation device, where: 37 H b = H rbc ( Q b - Q p )
Q b and where H.sub.rbc is a value relating to hematocrit of red
blood cells in the separation device.
2. A system according to claim 1 and further including an element
that generates a control command based, at least in part, upon
H.sub.b.
3. A system according to claim 2 wherein the control command
recirculates at least a portion of plasma constituent for mixing
with whole blood conveyed into the separation device.
4. A system according to claim 2 wherein the control command
controls Q.sub.b.
5. A system according to claim 1 and further including an element
that generates an output based, at least in part, upon H.sub.b.
6. A system according to claim 5 wherein the output comprises a
value .eta. representing efficiency of separation in the separation
device, where: 38 = Q p ( 1 - H b ) Q b
7. A system according to claim 1 wherein the value H.sub.rbc
represents apparent hematocrit of red blood cells in the separation
device, where: 39 H rbc = 1 - ( gA S ( q b - q p ) ) 1 k + 1 where:
q.sub.b is inlet blood flow rate (cm.sup.3/sec), which when
converted to ml/min, corresponds with Q.sub.b, q.sub.p is measured
plasma flow rate (in cm.sup.3/sec), which, when converted to ml/min
corresponds with Q.sub.p, .beta. is a shear rate dependent term,
and S.sub.Y is a red blood cell sedimentation coefficient (sec) and
.beta./S.sub.Y=15.8.times.10.sup.6 sec.sup.-1, A is the area of the
separation device (cm.sup.2), g is the centrifugal acceleration
(cm/sec.sup.2), which is the radius of the separation device
multiplied by the rate of rotation squared .OMEGA..sup.2
(rad/sec.sup.2), and k is a viscosity constant=0.625, and .kappa.
is a viscosity constant based upon k and another viscosity constant
.alpha.=4.5, where: 40 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272
8. A system according to claim 7 wherein the separation device is
free of an sensor to measure blood hematocrit.
9. A system according to claim 1 wherein the inlet path is free of
any sensor to measure blood hematocrit.
10. A blood processing system comprising a centrifugal separation
device rotatable at a prescribed rate of rotation, an inlet path
including a pump operable at a prescribed rate Q.sub.b to convey
whole blood into the separation device for separation into red
blood cells and a plasma constituent, an outlet path including a
pump operable at a prescribed rate Q.sub.p to remove plasma
constituent from the separation device, a recirculation path
including a pump operable at a prescribed rate Q.sub.Recirc to
recirculate at least a portion of the plasma constituent for mixing
with whole blood conveyed into the separation device, a controller
coupled to the recirculation path pump to set Q.sub.Recirc to
achieve a desired hematocrit H.sub.i for whole blood conveyed into
the separation device as follows: 41 Q Recirc = [ H b H i - 1 ]
.times. Q b where H.sub.b is a value representing an apparent
hematocrit of whole blood entering the separation device, where: 42
H b = H rbc ( Q b - Q p ) Q b and where H.sub.rbc is a value
relating to hematocrit of red blood cells in the separation device.
43 = Q b ( 1 - H b ) Q b
11. A system according to claim 10 wherein the value H.sub.rbc
represents apparent hematocrit of red blood cells in the separation
device, where: 44 H rbc = 1 - ( gA S ( q b - q p ) ) 1 k + 1 where:
q.sub.b is inlet blood flow rate (cm.sup.3/sec), which when
converted to ml/min, corresponds with Q.sub.b, q.sub.p is measured
plasma flow rate (in cm.sup.3/sec), which, when converted to ml/min
corresponds with Q.sub.p, .beta. is a shear rate dependent term,
and S.sub.Y is a red blood cell sedimentation coefficient (sec) and
.beta./S.sub.Y=15.8.times.10.sup.6 sec.sup.-1, A is the area of the
separation device (cm.sup.2), g is the centrifugal acceleration
(cm/sec.sup.2), which is the radius of the separation device
multiplied by the rate of rotation squared .OMEGA..sup.2
(rad/sec.sup.2), and k is a viscosity constant=0.625, and .kappa.
is a viscosity constant based upon k and another viscosity constant
.alpha.=4.5, where: 45 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272
12. A system according to claim 11 wherein the separation device is
free of an sensor to measure blood hematocrit.
13. A system according to claim 10 wherein the inlet path is free
of any sensor to measure blood hematocrit.
14. A system according to claim 10 wherein H.sub.i is no greater
than about 40%.
15. A system according to claim 1 wherein H.sub.i is about 32%.
16. A blood processing method comprising the steps of rotating a
centrifugal separation device at a prescribed rate of rotation,
conveying whole blood into the separation device at a prescribed
rate Q.sub.b for separation into red blood cells and a plasma
constituent, removing plasma constituent from the separation device
at a prescribed rate Q.sub.p, deriving a value H.sub.b representing
an apparent hematocrit of whole blood entering the separation
device, where: 46 H b = H rbc ( Q b - Q p ) Q b and where H.sub.rbc
is a value relating to hematocrit of red blood cells in the
separation device.
17. A method according to claim 16 and further including the step
of generating a control command based, at least in part, upon
H.sub.b.
18. A method according to claim 17 wherein the control command
recirculates at least a portion of plasma constituent for mixing
with whole blood conveyed into the separation device.
19. A method according to claim 17 wherein the control command
controls Q.sub.b.
20. A method according to claim 16 and further the step of
generating an output based, at least in part, upon H.sub.b.
21. A method according to claim 20 wherein the output comprises a
value .eta. representing efficiency of separation in the separation
device, where: 47 = Q b ( 1 - H b ) Q b
22. A method according to claim 16 wherein the value H.sub.rbc
represents apparent hematocrit of red blood cells in the separation
device, where: 48 H rbc = 1 - ( gA S ( q b - q p ) ) 1 k + 1 where:
q.sub.b is inlet blood flow rate (cm.sup.3/sec), which when
converted to ml/min, corresponds with Q.sub.b, q.sub.p is measured
plasma flow rate (in cm.sup.3/sec), which, when converted to ml/min
corresponds with Q.sub.p, .beta. is a shear rate dependent term,
and S.sub.Y is a red blood-cell sedimentation coefficient (sec) and
.beta./S.sub.Y=15.8.times.10.sup.6 sec.sup.-1, A is the area of the
separation device (cm.sup.2), g is the centrifugal acceleration
(cm/sec.sup.2), which is the radius of the separation device
multiplied by the rate of rotation squared .OMEGA..sup.2
(rad/sec.sup.2), and k is a viscosity constant=0.625, and .kappa.
is a viscosity constant based upon k and another viscosity constant
.alpha.4.5, where: 49 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272
23. A method according to claim 22 wherein the method is free of a
step of using a sensor to measure blood hematocrit in the
separation device.
24. A method according to claim 16 wherein the method is free of a
step of using a sensor to measure blood hematocrit in the inlet
path.
25. A blood processing method comprising the steps of rotating a
centrifugal separation device at a prescribed rate of rotation,
conveying whole blood into the separation device at a prescribed
rate Q.sub.b for separation into red blood cells and a plasma
constituent, removing plasma constituent from the separation device
at a prescribed rate Q.sub.p, recirculating at least a portion of
plasma constituent from the separation device at a prescribed rate
Q.sub.Recirc for mixing with whole blood conveyed into the
separation device, controlling Q.sub.Recirc to achieve a desired
hematocrit H.sub.i for whole blood conveyed into the separation
device as follows: 50 Q Recirc = [ H b H i - 1 ] .times. Q b
recirculating at least a portion of plasma constituent from the
separation device at a prescribed rate Q.sub.Recirc for mixing with
whole blood conveyed into the separation device, controlling
Q.sub.Recirc to achieve a desired hematocrit H.sub.i for whole
blood conveyed into the separation device as follows: 51 Q Recirc =
[ H b H i - 1 ] .times. Q b where H.sub.b is a value representing
an apparent hematocrit of whole blood entering the separation
device, where: 52 H b = H rbc ( Q b - Q p ) Q b and where H.sub.rbc
is a value relating to hematocrit of red blood cells in the
separation device.
26. A method according to claim 25 wherein the value H.sub.rbc
represents apparent hematocrit of red blood cells in the separation
device, where: 53 H rbc = 1 - ( gA S ( q b - q b ) ) 1 k + 1 where:
q.sub.b is inlet blood flow rate (cm.sup.3/sec), which when
converted to ml/min, corresponds with Q.sub.b, q.sub.p is measured
plasma flow rate (in cm.sup.3/sec), which, when converted to ml/min
corresponds with Q.sub.p, .beta. is a shear rate dependent term,
and S.sub.Y is a red blood cell sedimentation coefficient (sec) and
.beta./S.sub.Y=15.8.times.10.sup.6 sec.sup.-1, A is the area of the
separation device (cm.sup.2), g is the centrifugal acceleration
(cm/sec.sup.2), which is the radius of the separation device
multiplied by the rate of rotation squared .OMEGA..sup.2
(rad/sec.sup.2), and k is a viscosity constant=0.625, and .kappa.
is a viscosity constant based upon k and another viscosity constant
.alpha.=4.5, where: 54 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272
27. A method according to claim 26 wherein the method is free of a
step of using a sensor to measure blood hematocrit in the
separation device.
28. A method according to claim 25 wherein the method is free of a
step of using a sensor to measure blood hematocrit in the inlet
path.
Description
FIELD OF THE INVENTION
[0001] The invention generally relates to blood processing systems
and methods.
BACKGROUND OF THE INVENTION
[0002] Today people routinely separate whole blood by
centrifugation into its various therapeutic components, such as red
blood cells, platelets, and plasma.
[0003] 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.
[0004] 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 in 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 in a
sequential flow loop.
[0005] 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.times.10.sup.11 platelets suspended in 200 ml of fluid) can be
collected. Moreover, since the donor's red blood cells are
returned, the donor can donate whole blood for on line processing
much more frequently than donors for processing in multiple blood
bag systems.
[0006] Nevertheless, a need still exists for further improved
systems and methods for collecting cellular-rich concentrates 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 can be
realized.
[0007] As the operational and performance demands upon such fluid
processing systems become more complex and sophisticated, the need
exists for automated process controllers that can gather and
generate more detailed information and control signals to aid the
operator in maximizing processing and separation efficiencies.
SUMMARY OF THE INVENTION
[0008] The invention provides blood processing systems and methods
that separate whole blood into red blood cells and a plasma
constituent within a rotating centrifugal separation device. The
systems and methods convey whole blood into the separation device
through an inlet path including a pump operable at a prescribed
rate. The systems and methods remove plasma constituent from the
separation device through an outlet path including a pump operable
at a prescribed rate.
[0009] According to the invention, the systems and methods derive a
value H.sub.b representing an apparent hematocrit of whole blood
entering the separation device, where: 2 H b = H rbc ( Q b - Q p )
Q b
[0010] and where H.sub.rbc is a value relating to hematocrit of red
blood cells in the separation device.
[0011] In a preferred embodiment, the systems and methods generate
a control command based, at least in part, upon H.sub.b. In one
implementation, the control command recirculates at least a portion
of plasma constituent for mixing with whole blood conveyed into the
separation device. In another implementation, the control command
controls
[0012] In a preferred embodiment, the systems and methods generate
an output based, at least in part, upon H.sub.b. In one
implementation, the output comprises a value .eta. representing
efficiency of separation in the separation device, where: 3 = Q p (
1 - H b ) Q b
[0013] In a preferred embodiment, the value H.sub.rbc represents
apparent hematocrit of red blood cells in the separation device,
where: 4 H rbc = 1 - ( gA S ( q b - q p ) ) 1 k + 1
[0014] where:
[0015] q.sub.b is inlet blood flow rate (cm.sup.3/sec), which when
converted to ml/min, corresponds with Q.sub.b,
[0016] q.sub.p is measured plasma flow rate (in cm.sup.3/sec),
which, when converted to ml/min corresponds with Q.sub.p,
[0017] .beta. is a shear rate dependent term, and S.sub.Y is a red
blood cell sedimentation coefficient (sec) and
.beta./S.sub.Y=15.8.times.10.sup- .6 sec.sup.-1,
[0018] A is the area of the separation device (cm.sup.2),
[0019] g is the centrifugal acceleration (cm/sec.sup.2), which is
the radius of the separation device multiplied by the rate of
rotation squared .OMEGA..sup.2 (rad/sec.sup.2), and
[0020] k is a viscosity constant=0.625, and .kappa. is a viscosity
constant based upon k and another viscosity constant .alpha.=4.5,
where: 5 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272
[0021] In a preferred embodiment, the systems and methods operate
free of any a sensor to measure blood hematocrit either in the
separation device or in the inlet path.
[0022] In a preferred embodiment, the systems and methods
recirculate at least a portion of plasma constituent from the
separation device at a prescribed rate Q.sub.Recirc for mixing with
whole blood conveyed into the separation device. In this
embodiment, the systems and methods control Q.sub.Recirc to achieve
a desired hematocrit H.sub.i for whole blood conveyed into the
separation device as follows: 6 Q Recirc = [ H b H i - 1 ] .times.
Q b
[0023] The various aspects of the invention are especially well
suited for on line blood separation processes.
[0024] Other features and advantages of the invention will become
apparent from the following description, the drawings, and the
claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] FIG. 1 is a diagrammatic view of a dual needle platelet
collection system that includes a controller that embodies the
features of the invention;
[0026] FIG. 2 is a diagrammatic flow chart view of the controller
and associated system optimization application that embodies the
features of the invention;
[0027] FIG. 3 is a diagrammatic view of the function utilities
contained within the system optimization application shown in FIG.
2;
[0028] 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 processing
session;
[0029] FIG. 5 is a diagrammatic flow chart view of the utility
functions contained within the system optimization application that
provide processing status and parameter information, generate
control variables for achieving optimal separation efficiencies,
and generate control variables that control the rate of citrate
infusion during a given processing session;
[0030] FIG. 6 is a diagrammatic flow chart view of the utility
function contained within the system optimization application that
recommends optimal storage parameters based upon the yield of
platelets during a given processing session;
[0031] FIG. 7 is a diagrammatic flow chart view of the utility
function contained within the system optimization application that
estimates the processing time before commencing a given processing
session;
[0032] 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;
[0033] FIG. 9 is a graph showing the relationship between the
partial pressure of oxygen and the permeation of a particular
storage container, which the utility function shown in FIG. 6 takes
into account in recommending optimal storage parameters in terms of
the number of storage containers;
[0034] FIG. 10 is a graph showing the relationship between the
consumption of bicarbonate and storage thrombocytocrit for a
particular storage container, which the utility function shown in
FIG. 6 takes into account in recommending optimal storage
parameters I n terms of the volume of plasma storage medium;
and
[0035] FIG. 11 is a graph showing the efficiency of platelet
separation, expressed in terms of mean platelet volume, in terms of
inlet hematocrit, which a utility function shown in FIG. 5 takes
into account in generating a control variable governing plasma
recirculation during processing.
[0036] The various aspects of 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.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0037] FIG. 1 shows in diagrammatic form an on line blood
processing system 10 for carrying out an automated platelet
collection procedure. 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
includes a processing controller 18 embodying the features of the
invention.
I. The Separation System
[0038] The system 10 includes an arrangement of durable hardware
elements, whose operation is governed by the processing controller
18. The hardware elements include a centrifuge 12, in which whole
blood (WB) is separated into its various therapeutic components,
like platelets, plasma, and red blood cells (RBC). The hardware
elements will also include various pumps, which are typically
peristaltic (designated P1 to P4); and various in line clamps and
valves (designated V1 to V3). Of course, other types of hardware
elements may typically be present, which FIG. 1 does not show, like
solenoids, pressure monitors, and the like.
[0039] The system 10 typically also includes some form of a
disposable fluid processing assembly 14 used in association with
the hardware elements.
[0040] In the illustrated blood processing system 10, the assembly
14 includes a two stage processing chamber 16. In use, the
centrifuge 12 rotates the processing chamber 16 to centrifugally
separate blood components. A representative centrifuge that can be
used is shown in Williamson et al U.S. Pat. No. 5,360,542, which is
incorporated herein by reference.
[0041] 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 in Cullis et al. U.S. Pat. No. 4,146,172.
Alternatively, the processing chamber 16 can take the form of an
elongated two stage integral bag, like that shown in Brown U.S.
Pat. No. 5,370,802.
[0042] 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-P4 and the valves
V1-V3 engage the tubing to govern the fluid flow in prescribed
ways. The fluid circuit further includes a number of containers
(designated C1 to C3) to dispense and receive liquids during
processing.
[0043] The 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 invention specifically concerns important
attributes of the controller 18.
[0044] 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 two needle platelet collection
procedure.
[0045] 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. Meanwhile, an auxiliary
tubing branch 26 meters anticoagulant from the container C1 to the
WB flow through the anticoagulant pump P1. While the type of
anticoagulant can vary, the illustrated embodiment uses ACDA, which
is a commonly used anticoagulant for pheresis.
[0046] The container C2 holds saline solution. Another auxiliary
tubing branch 28 conveys the saline into the first tubing branch
20, via the in line valve V1, for use in priming and purging air
from the system 10 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.
[0047] Anticoagulated WB enters and fills the first stage 24 of the
processing chamber 24. There, centrifugal forces generated during
rotation of the centrifuge 12 separate WB into red blood cells
(RBC) and platelet-rich plasma (PRP).
[0048] The 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).
[0049] Optionally, the PRP can 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. Pat. No. 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 SEPACELL.
[0050] 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 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.
[0051] 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 branches 38 and 40 and in line
valve V2.
[0052] The system 10 also collects PC (resuspended 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 container(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 (as disclosed in
Gajewski et al U.S. Pat. No. 4,140,162), or a polyvinyl chloride
material plasticized with tri-2-ethylhexyl trimellitate (TEHTM) can
be used.
[0053] 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 purposes, both during and after the component
separation process.
[0054] 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.
[0055] The system 10 can also derive processing benefits from the
retained PPP.
[0056] 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 draws 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 40. 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
compartment 24 for transfer and storage in the collection
container(s) C3.
II. The System Controller
[0057] The controller 18 carries out the overall process control
and monitoring functions for the system 10 as just described.
[0058] 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.
[0059] 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. Functional Hardware Control
[0060] The MPU 44 includes an application control manager 46. The
application control manager 46 administers the activation of a
library 48 of control applications (designated A1 to A3). Each
control application A1-A3 prescribes procedures for carrying out
given functional tasks using the system hardware (e.g., the
centrifuge 12, the pumps P1-P4, and the valves V1-V3) in a
predetermined way. In the illustrated and preferred embodiment, the
applications A1-A3 reside as process software in EPROM's in the MPU
44.
[0061] The number of applications A1-A3 can vary. In the
illustrated and preferred embodiment, the library 48 includes at
least one clinical procedure application A1. The procedure
application A1 contains the steps to carry out one prescribed
clinical processing procedure. For the sake of example in the
illustrated embodiment, the library 48 includes a procedure
application A1 for carrying out the dual needle platelet collection
process, as already generally described in connection with FIG. 1.
Of course, additional procedure applications can be, and typically
will be, included. For example, the library 48 can include a
procedure application for carrying out a conventional single needle
platelet collection process.
[0062] In the illustrated and preferred embodiment, the library 48
also includes a system optimization application A2. The system
optimization application A2 contains interrelated, specialized
utility functions 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 optimization application A2 will be
described later.
[0063] The library 48 also includes a main menu application A3,
which coordinates the selection of the various applications A1-A3
by the operator, as will also be described in greater detail
later.
[0064] Of course, additional non-clinical procedure applications
can be, and typically will be, included. For example, the library
48 can include a configuration application, which contains the
procedures for allowing the operator to configure the default
operating parameters of the system 10. As a further example, the
library 48 can include a diagnostic application, which contains the
procedures 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.
[0065] An 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.
[0066] 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 A1-A3. 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.
[0067] 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.
[0068] 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 A1 and the performance monitoring application A2.
B. User Interface Control
[0069] 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.
[0070] 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 alpha-numeric format and
as graphical images. The audio device 62 provides audible prompts
either to gain the operator's attention or to acknowledge operator
actions.
[0071] 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.
[0072] An interface controller 64 communicates with the interface
screen 60 and audio device 62. The interface controller 64, in
turn, communicates with an interface manager 66, which in turn
communicates with the application control manager 46. The interface
controller 64 and the interface manager 66 reside as process
software in EPROM's in the MPU 44.
[0073] Further details of the interface 58 are disclosed in
copending application Serial No. xxx.
C. The System Optimization
Application
[0074] In the illustrated embodiment (as FIG. 3 shows), the system
optimization application A2 contains six specialized yet
interrelated utility functions, designated F1 to F6. Of course, the
number and type of utility functions can vary.
[0075] In the illustrated embodiment, a utility function F1 derives
the yield of the system 10 for the particular cellular component
targeted for collection. For the platelet collection procedure
application A1, the utility function F1 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 F1 derive the instantaneous yield of platelets
continuously over the processing period.
[0076] Yet another utility function F2 relies upon the calculated
platelet yield 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.
[0077] Another utility function F3 calculates and recommends, based
upon the platelet yield derived by the utility function F1, the
optimal storage parameters for the platelets in terms of the number
of storage containers and the volume amount of PPP storage media to
use.
[0078] 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 F4 generates control
variables to optimize platelet separation conditions in the 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 toxicity
reactions.
[0079] Yet another utility function F6 derives an estimated
procedure time, which predicts the collection time before the donor
is connected.
[0080] Further details of these utility functions F1 to F6 will now
be described in greater detail.
III. Deriving Platelet Yield
[0081] The utility function F1 (see FIG. 4) makes continuous
calculations of the platelet separation efficiency (.eta..sub.PLt)
of the system 10. The utility function F1 treats the platelet
separation efficiency .eta..sub.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 F1 thereby assumes that every platelet in the plasma
volume separated from the donor's whole blood will be
harvested.
[0082] The donor's hematocrit changes due to anticoagulant dilution
and plasma depletion effects during processing, so the separation
efficiency .eta..sub.PLt does not remain at a constant value, but
changes throughout the procedure. The utility function F1 contends
with these process-dependent changes by monitoring yields
incrementally. These yields, called incremental cleared volumes
(.DELTA.ClrVol), are calculated by multiplying the current
separation efficiency .eta..sub.PLt by the current incremental
volume of donor whole blood, diluted with anticoagulant, being
processed, as follows:
.DELTA.ClrVol=ACDil.times..eta..sub.Plt.times..DELTA.VOL.sub.Proc
Eq (1)
[0083] where:
[0084] .DELTA.Vol.sub.Proc is the incremental whole blood volume
being processed, and
[0085] ACDil is an anticoagulant dilution factor for the
incremental whole blood volume, computed as follows: 7 ACDil = AC
AC + 1 Eq (2)
[0086] where:
[0087] 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.
[0088] 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.
[0089] 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.
[0090] The utility function F1 also makes continuous estimates of
the donor's current circulating platelet count (Plt.sub.Circ) ,
expressed in terms of 1000 platelets per microliter (.mu.l) of
plasma volume (or k/.mu.l). Like .eta..sub.PLt, Plt.sub.Circ will
change during processing due to the effects of dilution and
depletion. The utility function F1 incrementally monitors the
platelet yield in increments, too, by multiplying each incremental
cleared plasma volume .DELTA.ClrVol (based upon an instantaneous
calculation of .eta..sub.PLt) by an instantaneous estimation of the
circulating platelet count Plt.sub.Cir. The product is an
incremental platelet yield (.DELTA.yld), typically expressed as
e.sup.n platelets, where e.sup.n=0.5.times.1 .sup.n0 platelets
(e.sup.11=0.5.times.10.sup.11 platelets).
[0091] At any given time, the sum of the incremental platelet
yields .DELTA.Yld constitutes the current platelet yield
Yld.sub.Current, which can also be expressed as follows: 8 Yld
Current = Yld Old + ClrVol .times. Plt Cur 100 , 000 Eq (3)
[0092] where:
[0093] Yld.sub.Old is the last calculated Yld.sub.Current, and 9
Yld = ClrVol .times. Plt Current 100 , 000 Eq (4)
[0094] where:
[0095] Plt.sub.Current is the current (instantaneous) estimate of
the circulating platelet count of the donor.
[0096] .DELTA.Yld is divided by 100,000 in Eq (4) to balance
units.
[0097] The following provides further details in the derivation of
the above-described processing variables by the utility function
F1.
A. Deriving Overall Separation Efficiency .eta..sub.PLt
[0098] The overall system efficiency .eta..sub.PLt is the product
of the individual efficiencies of the parts of the system, as
expressed as follows:
.eta..sub.plt=.eta..sub.1stSep.times..eta..sub.2ndSep.times..eta..sub.Anc
Eq (5)
[0099] where:
[0100] .eta..sub.1stSep is the efficiency of the separation of PRP
from WB in the first separation stage.
[0101] .eta..sub.2ndSep is the efficiency of separation PC from PRP
in the second separation stage.
[0102] .eta..sub.Anc is the product of the efficiencies of other
ancillary processing steps in the system.
1. First Stage Separation Efficiency .eta..sub.1stSep
[0103] The utility function F1 (see FIG. 4) derives
.eta..sub.1stSep continuously over the course of a procedure based
upon measured and empirical processing values, using the following
expression: 10 Sep = Q p ( 1 - H b ) Q b Eq (6)
[0104] where:
[0105] Q.sub.b is the measured whole blood flow rate (in
ml/min).
[0106] Q.sub.p is the measured PRP flow rate (in ml/min).
[0107] H.sub.b is the apparent hematocrit of the anticoagulated
whole blood entering the first stage separation compartment.
H.sub.b is a value derived by the utility based upon sensed flow
conditions and theoretical considerations. The utility function F1
therefore requires no on-line hematocrit sensor to measure actual
WB hematocrit.
[0108] The utility function F1 derives H.sub.b based upon the
following relationship: 11 H b = H rbc ( Q b - Q p ) Q b Eq (7)
[0109] where:
[0110] H.sub.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.sub.b, the utility function F1
requires no physical sensor to determine H.sub.rbc, which is
derived by the utility function according to the following
expression: 12 H rbc = 1 - ( gA S ( q b - q p ) ) 1 k + 1 Eq
(8)
[0111] where:
[0112] q.sub.b is inlet blood flow rate (cm.sup.3/sec), which is a
known quantity which, when converted to ml/min, corresponds with
Q.sub.b in Eq (6).
[0113] q.sub.p is measured PRP flow rate (in cm.sup.3/sec), which
is a known quantity which, when converted to ml/min corresponds
with Q.sub.p in Eq (6).
[0114] .beta. is a shear rate dependent term, and S.sub.Y is the
red blood cell sedimentation coefficient (sec). Based upon
empirical data, Eq (8) assumes that
.beta./S.sub.Y=15.8.times.10.sup.6 sec.sup.-1.
[0115] A is the area of the separation chamber (cm.sup.2), which is
a known dimension.
[0116] g is the centrifugal acceleration (cm/sec.sup.2), which is
the radius of the first separation chamber (a known dimension)
multiplied by the rate of rotation squared .OMEGA..sup.2 (rad/sec)
(another known quantity).
[0117] k is a viscosity constant=0.625, and .kappa. is a viscosity
constant based upon k and another viscosity constant .alpha.=4.5,
where: 13 = k + 2 [ k + 2 k + 1 ] k + 1 = 1.272 Eq (9)
[0118] Eq (8) is derived from the relationships expressed in the
following Eq (10): 14 H rbc ( 1 - H rbc ) ( k + 1 ) = H b q b g A S
Eq (10)
[0119] 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.sub.rbc.
2. The Second Stage Separation Efficiency .eta..sub.2ndSep
[0120] The utility function F1 (see FIG. 4) also derives
.eta..sub.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.sub.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 .OMEGA..sup.2).
[0121] The algorithm can be expressed in terms of a function shown
graphically in FIG. 8. The graph plots .eta..sub.2ndSep in terms of
a single dimensionless parameter gAS.sub.p/Q.sub.p,
[0122] where:
[0123] S.sub.p=1.8.times.10.sup.-9 MPV.sup.2/3(sec), and
[0124] 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.sub.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).about.11.5-0.009Plt.sub.PRE (k/.mu.l)
3. Ancillary Separation Efficiencies .eta..sub.Anc
[0125] .eta..sub.Anc takes into account the efficiency (in terms of
platelet loss) of other portions of the processing system.
.eta..sub.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.
[0126] 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
.eta..sub.Anc can be assigned, which Eq (5) treats as constant over
the course of a given procedure.
B. Deriving Donor Platelet Count (Plt.sub.Circ)
[0127] The utility function F1 (see FIG. 4) relies upon a kinetic
model to predict the donor's current circulating platelet count
Plt.sub.Circ during processing. The model estimates the donor's
blood volume, and then estimates the effects of dilution and
depletion during processing, to derive Plt.sub.Circ, according to
the following relationships:
Plt.sub.Circ=[(Dilution).times.Plt.sub.pre]-(Depletion) Eq (11)
[0128] where:
[0129] Plt.sub.pre is the donor's circulating platelet count before
processing begins (k/.mu.l), 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.sub.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.sub.pre and Pltpost,
described later) for use by the function according to the type of
counter used.
[0130] Dilution is a factor that reduces the donor's preprocessing
circulating platelet count Plt.sub.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. Dilution
also takes into account the continuous removal of fluid from the
vascular space by the kidneys during the procedure.
[0131] 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
[0132] The utility function F1 estimates the dilution factor based
upon the following expression: 15 Dilution = 1 - Prime + 2 ACD 3 -
PPP DonVol Eq (12)
[0133] where:
[0134] Prime is the priming volume of the system (ml).
[0135] ACD is the volume of anticoagulant used (current or
end-point, depending upon the time the derivation, is made)
(ml).
[0136] PPP is the volume of PPP collected (current or goal)
(ml).
[0137] 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:
DonVol=1024+51Wgt(r.sup.2=0.87) Eq (13)
[0138] where:
[0139] Wgt is the donor's weight (kg).
2. Estimating Depletion
[0140] 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: 16 Depl = 100 , 000 Yld
DonVol Eq (14)
[0141] where:
[0142] Yld is the current instantaneous or goal platelet yield
(k/.mu.l). In Eq (14), Yld is multiplied by 100,000 to balance
units.
[0143] Eq (14) does not take into account splenic mobilization of
replacement platelets, which is called the splenic mobilization
factor (or Spleen). 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.
[0144] The inventor has derived the mobilization factor Spleen from
comparing actual measured depletion to Depl (Eq (14)), which is
plotted and linearized as a function of Plt.sub.Pre. Spleen (which
is restricted to a lower limit of 1) is set forth as follows:
Spleen=[2.25-0.004 Plt.sub.Pre].gtoreq.1 Eq (15)
[0145] Based upon Eqs (14) and (15), the utility function derives
Depletion as follows: 17 Depletion = 100 , 000 Yld Spleen .times.
DonVol Eq (16)
C. Real Time Procedure Modifications
[0146] The operator will not always have a current platelet
pre-count Plt.sub.Pre for every donor at the beginning of the
procedure. The utility function F1 allows the system to launch
under default parameters, or values from a previous procedure. The
utility function F1 allows the actual platelet pre-count
Plt.sub.Pre, to be entered by the operator later during the
procedure. The utility function F1 recalculates platelet yields
determined under one set of conditions to reflect the newly entered
values. The utility function F1 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.
[0147] The utility function F1 uses the current yield to calculate
an effective cleared volume as follows: 18 lrVol = 100 , 000
.times. DonVol .times. Yld Current [ DonVol - Prime - ACD 3 + PPP 2
] .times. Pre old - 50 , 000 .times. Yld current Spleen Old Eq
(17)
[0148] where:
[0149] ClrVol is the cleared plasma volume.
[0150] DonVol is the donor's circulating blood volume, calculated
according to Eq (13).
[0151] Yld.sub.Current is the current platelet yield calculated
according to Eq (3) based upon current processing conditions.
[0152] Prime is the blood-side priming volume (ml).
[0153] ACD is the volume of anticoagulant used (ml).
[0154] PPP is the volume of platelet-poor plasma collected
(ml).
[0155] Pre.sub.OLd is the donor's platelet count before processing
entered before processing begun (k/.mu.l).
[0156] Spleen.sub.OLd is the splenic mobilization factor calculated
using Eq (16) based upon Pre.sub.OLd.
[0157] The utility function F1 uses ClrVol calculated using Eq (17)
to calculate the new current yield as follows: 19 Yld New = [
DonVol - Prime - ACD 3 + PPP 2 DonVol + ClrVol 2 .times. Spleen New
] .times. [ ClrVol .times. Pre New 100 , 000 ] Eq (18)
[0158] where:
[0159] Pre.sub.New is the revised donor platelet pre-count entered
during processing (k/.mu.l).
[0160] Yld.sub.New is the new platelet yield that takes into
account the revised donor platelet pre-count Pre.sub.New.
[0161] ClrVol is the cleared plasma volume, calculated according to
Eq (17).
[0162] DonVol is the donor's circulating blood volume, calculated
according to Eq (13), same as in Eq (17).
[0163] Prime is the blood-side priming volume (ml), same as in Eq
(17).
[0164] ACD is the volume of anticoagulant used (ml), same as in Eq
(17).
[0165] PPP is the volume of platelet-poor plasma collected (ml),
same as in Eq (17).
[0166] Spleen.sub.New is the splenic mobilization factor calculated
using Eq (15) based upon Pre.sub.New.
IV. Deriving Other Processing Information
[0167] The utility function F2 (see FIG. 5) relies upon the
calculation of Yld by the first utility function F1 to derive other
informational values and parameters to aid the operator in
determining the optimum operating conditions for the procedure. The
follow processing values exemplify derivations that the utility
function F2 can provide.
A. Remaining Volume to be Processed
[0168] The utility function F2 calculates the additional processed
volume needed to achieve a desired platelet yield Vb.sub.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
.eta..sub.PLt. The utility function F2 derives this value using the
following expression: 20 Vb rem = 200 , 000 .times. ( Yld Goal -
Yld Current ) Plt .times. ACDil .times. ( Plt Current + Plt Post )
Eq (19)
[0169] where:
[0170] Yld.sub.GoaL is the desired platelet yield (k/.mu.l),
[0171] where:
[0172] Vb.sub.rem is the additional processing volume (ml) needed
to achieve Yld.sub.GoaL.
[0173] Yld.sub.Current is the current platelet yield (k/.mu.l),
calculated using Eq (3) based upon current processing values.
[0174] .eta..sub.PLt is the present (instantaneous) platelet
collection efficiency, calculated using Eq (5) based upon current
processing values.
[0175] ACDil is the anticoagulant dilution factor (Eq (2)).
[0176] Plt.sub.current is the current (instantaneous) circulating
donor platelet count, calculated using Eq (11) based upon current
processing values.
[0177] Plt.sub.Post is the expected donor platelet count after
processing, also calculated using Eq (11) based upon total
processing values.
B. Remaining Procedure Time
[0178] The utility function F2 also calculates remaining collection
time (t.sub.rem) (in min) as follows: 21 t rem = Vb rem Q b Eq
(20)
[0179] where:
[0180] Vb.sub.rem is the remaining volume to be processed,
calculated using Eq (19) based upon current processing
conditions.
[0181] Qb is the whole blood flow rate, which is either set by the
user or calculated as Qb.sub.Opt using Eq (31), as will be
described later.
C. Plasma Collection
[0182] The utility function F2 adds the various plasma collection
requirements to derive the plasma collection volume (PPP.sub.GoaL)
(in ml) as follows:
PPP.sub.Goal=PPP.sub.PC+PPP.sub.Source+PPP.sub.Reinfuse+PPP.sub.Waste+PPP.-
sub.CollCham Eq (21)
[0183] where:
[0184] PPP.sub.PC is the platelet-poor plasma volume selected for
the PC product, which can have a typical default value of 250 ml,
or be calculated as an optimal value Plt.sub.Med according to Eq
(28), as will be described later.
[0185] PPP.sub.Source is the platelet-poor plasma volume selected
for collection as source plasma.
[0186] PPP.sub.Waste is the platelet-poor plasma volume selected to
be held in reserve for various processing purposes (Default=30
ml).
[0187] PPP.sub.CoLLCham is the volume of the plasma collection
chamber (Default=40 ml).
[0188] PPP.sub.Reinfuse is the platelet-poor plasma volume that
will be reinfusion during processing.
D. Plasma Collection Rate
[0189] The utility function F2 calculates the plasma collection
rate (Q.sub.PPP) (in ml/min) as follows: 22 Q PPP = PPP Goal - PPP
Current t rem Eq (22)
[0190] where:
[0191] PPP.sub.GoaL is the desired platelet-poor plasma collection
volume (ml).
[0192] PPP.sub.Current is the current volume of platelet-poor
plasma collected (ml).
[0193] t.sub.rem is the time remaining in collection, calculated
using Eq (20) based upon current processing conditions.
E. Total Anticipated AC Usage
[0194] The utility function F2 can also calculate the total volume
of anticoagulant expected to be used during processing
(ACD.sub.End) (in ml) as follows: 23 ACD End = ACD Current + Q b
.times. t rem 1 + AC Eq (23)
[0195] where:
[0196] ACD.sub.Current is the current volume of anticoagulant used
(ml).
[0197] AC is the selected anticoagulant ratio,
[0198] Q.sub.b is the whole blood flow rate, which is either set by
the user or calculated using Eq (31) as Qb.sub.Opt based upon
current processing conditions.
[0199] t.sub.rem is the time remaining in collection, calculated
using Eq (20) based upon current processing conditions.
V. Recommending Optimum Platelet Storage Parameters
[0200] The utility function F3 (see FIG. 6) relies upon the
calculation of Yld by the utility function F1 to aid the operator
in determining the optimum storage conditions for the platelets
collected during processing.
[0201] The utility function F3 derives the optimum storage
conditions to sustain the platelets during the expected storage
period in terms of the number of preselected storage containers
required for the platelets Plt.sub.Bag and the volume of plasma
(PPP) Plt.sub.Med (in ml) to reside as a storage medium with the
platelets.
[0202] The optimal storage conditions for platelets depends upon
the volume being stored Plt.sub.VoL, expressed as follows:
Plt.sub.Vol=Yld.times.MPV Eq (24)
[0203] where:
[0204] Yld is the number of platelets collected, and
[0205] MPV is the mean platelet volume.
[0206] As Plt.sub.VoL increases, so too does the platelets' demand
for oxygen during the storage period. As Plt.sub.VoL increases, the
platelets' glucose consumption to support metabolism and the
generation of carbon dioxide and lactate as a result of metabolism
also increase. The physical characteristics of the storage
containers in terms of surface area, thickness, 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.
[0207] The plasma storage medium contains bicarbonate HCO.sub.3,
which buffers the lactate generated by platelet metabolism, keeping
the pH at a level to sustain platelet viability. As Plt.sub.VoL
increases, the demand for the buffer effect of HCO.sub.3, and thus
more plasma volume during storage, also increases.
A. Deriving Plt.sub.Bag
[0208] The partial pressure of oxygen pO.sub.2 (mmHg) of platelets
stored within a storage container having a given permeation
decreases in relation to the total platelet volume Plt.sub.VoL the
container holds. FIG. 9 is a graph based upon test data showing the
relationship between pO.sub.2 measured after one day of storage for
a storage container of given permeation. The storage container upon
which FIG. 9 is based has a surface area of 54.458 in.sup.2 and a
capacity of 1000 ml. The storage container has a permeability to
O.sub.2 of 194 cc/100 in.sup.2/day, and a permeability to CO.sub.2
1282 cc/100 in.sup.2/day.
[0209] When the partial pressure pO.sub.2 drops below 20 mmHg,
platelets are observed to become anaerobic, and the volume of
lactate byproduct increases significantly. FIG. 9 shows that the
selected storage container can maintain pO.sub.2 of 40 mmHg (well
above the aerobic region) at Plt.sub.VoL.ltoreq.4.0 ml. On this
conservative basis, the 4.0 ml volume is selected as the target
volume Plt.sub.TVoL for this container. Target volumes Plt.sub.TVoL
for other containers can be determined using this same
methodology.
[0210] The utility function F3 uses the target platelet volume
Plt.sub.TVoL to compute Plt.sub.Bag as follows: 24 BAG = Plt Vol
Plt TVol Eq (25)
[0211] and:
[0212] Plt.sub.Bag=1 when BAG.ltoreq.1.0, otherwise
[0213] Plt.sub.Bag=[BAG+1], where [BAG+1] is the integer part of
the quantity BAG+1.
[0214] For example, given a donor MPV of 9.5 fl, and a Yld of
4.times.10.sup.11 platelets (Plt.sub.VoL=3.8 ml), and given
Plt.sub.TVoL=4.0 ml, BAG=0.95, and Plt.sub.Bag=1. If the donor MPV
is 11.0 fl and the yield Yld and Plt.sub.TVoL remain the same
(Plt.sub.VoL=4.4 ml), BAG=1.1 and Plt.sub.Bag=2.
[0215] When Plt.sub.Bag>1, Plt.sub.VoL is divided equally among
the number of containers called for.
B. Deriving Plt.sub.Med
[0216] The amount of bicarbonate used each day is a function of the
storage thrombocytocrit Tct (%), which can be expressed as follows:
25 Tct = Plt Vol Plt Med Eq (26)
[0217] The relationship between bicarbonate HCO.sub.3 consumption
per day and Tct can be empirically determined for the selected
storage container. FIG. 10 shows a graph showing this relationship
for the same container that the graph in FIG. 9 is based upon. The
y-axis in FIG. 10 shows the empirically measured consumption of
bicarbonate per day (in Meq/L) based upon Tct for that container.
The utility function F3 includes the data expressed in FIG. 10 in a
look-up table.
[0218] The utility function F3 derives the anticipated decay of
bicarbonate per day over the storage period .DELTA.HCO.sub.3 as
follows: 26 HCO 3 = Don HCO e Stor Eq (27)
[0219] where:
[0220] Don.sub.HCO3 is the measured bicarbonate level in the
donor's blood (Meq/L), or alternatively, is the bicarbonate level
for a typical donor, which is believed to be 19.0 Meq/L.+-.1.3,
and
[0221] Stor is the desired storage interval (in days, typically
between 3 to 6 days).
[0222] Given .DELTA.HCO.sub.3, the utility function F3 derives Tct
from the look up table for selected storage container. For the
storage container upon which FIG. 10 is based, a Tct of about 1.35
to 1.5% is believed to be conservatively appropriate in most
instances for a six day storage interval.
[0223] Knowing Tct and Plt.sub.VoL, the utility function F3
computes Plt.sub.Med based upon Eq (25), as follows: 27 Plt Med =
Plt Vol Tct 100 Eq (28)
[0224] When Plt.sub.Bag>1, Plt.sub.Med is divided equally among
the number of containers called for. PPP.sub.PC is set to
Plt.sub.Med in Eq (21).
VI. Deriving Control Variables
[0225] The utility functions F4 and F5 rely upon the
above-described matrix of physical and physiological relationships
to derive process control variables, which the application control
manager 46 uses to optimize system performance. The follow control
variables exemplify derivations that the utility functions F4 and
F5 can provide for this purpose.
A. Promoting High Platelet Separation Efficiencies By
Recirculation
[0226] A high mean platelet value MPV for collected platelets is
desirable, as it denotes a high separation efficiency for the first
separation stage and the system overall. Most platelets average
about 8 to 10 femtoliters, as measured by the Sysmex K-1000 machine
(the smallest of red blood cells begin at about 30 femtoliters).
The remaining minority of the platelet population constitutes
platelets that are physically larger. These larger platelets
typically occupy over 15.times.10.sup.-15 liter per platelet, and
some are larger than 30 femtoliters.
[0227] These larger platelets settle upon the RBC interface in the
first separation chamber quicker than most platelets. These larger
platelets are most likely to become entrapped in the RBC interface
and not enter the PRP for collection. Efficient separation of
platelets in the first separation chamber lifts the larger
platelets from the interface for collection in the PRP. This, in
turn, results a greater population of larger platelets in the PRP,
and therefore a higher MPV.
[0228] FIG. 11, derived from clinical data, shows that the
efficiency of platelet separation, expressed in terms of MPV, is
highly dependent upon the inlet hematocrit of WB entering the first
stage processing chamber. This is especially true at hematocrits of
30% and below, where significant increases in separation
efficiencies can be obtained.
[0229] Based upon this consideration, the utility function F4 sets
a rate for recirculating PRP back to the inlet of the first
separation stage Q.sub.Recirc to achieve a desired inlet hematocrit
H.sub.i selected to achieve a high MPV. The utility function F4
selects H.sub.i based upon the following red cell balance equation:
28 Q Recirc = [ H b H i - 1 ] .times. Q b Eq (29)
[0230] In a preferred implementation, H.sub.i is no greater that
about 40%, and, most preferably, is about 32%.
B. Citrate Infusion Rate
[0231] Citrate in the anticoagulant is rapidly metabolized by the
body, thus allowing its continuous infusion in returned PPP during
processing. However, at some level of citrate infusion, donors will
experience citrate toxicity. These reactions vary in both strength
and nature, and different donors have different 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 donors can tolerate
apheresis comfortably at an anticoagulated blood flow rates of 45
ml/min with an anticoagulant (ACD-A anticoagulant) ratio of
10:1.
[0232] 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 procedure,
which the system accomplishes. By doing so, the donor can be run at
a higher flow rate than would be expected otherwise. The maximum
a-symptomatic equivalent blood flow rate (EqQb.sub.CIR) (in ml/min)
under these conditions is believed to be: 29 EqQb CIR = CIR .times.
( AC + 1 ) .times. Wgt CitrateConc Eq (30)
[0233] where:
[0234] CIR is the selected nominal a-symptomatic citrate infusion
rate, or 1.25 mg/kg/min.
[0235] AC is the selected anticoagulant ratio, or 10:1.
[0236] Wgt is the donor's weight (kg).
[0237] CitrateConc is the citrate concentration in the selected
anticoagulant, which is 21.4 mg/ml for ACD-A anticoagulant.
C. Optimum Anticoagulated Blood Flow
[0238] The remaining volume of plasma that will be returned to the
donor is equal to the total amount available reduced by the amount
still to be collected. This ratio is used by the utility function
F5 (see FIG. 5) to determine the maximum, or optimum, a-symptomatic
blood flow rate (Qb.sub.Opt) (in ml/min) that can be drawn from the
donor, as follows: 30 Qb Opt = ( 1 - H b ) .times. Vb rem ( 1 - H b
) .times. Vb rem - ( PPP Goal - PPP Current ) .times. EqQb CIR Eq
(31)
[0239] where:
[0240] H.sub.b is the anticoagulated hematocrit, calculated using
Eq (7) based upon current processing conditions.
[0241] Vb.sub.Rem is the remaining volume to be processed,
calculated using Eq (19) based upon current processing
conditions.
[0242] EqQB.sub.CIR is the citrate equivalent blood flow rate,
calculated using Eq (30) based upon current processing
conditions.
[0243] PPP.sub.Goal is the total plasma volume to be collected
(ml).
[0244] PPP.sub.Current is the current plasma volume collected
(ml).
VII. Estimated Procedure Time
[0245] The utility function F6 (see FIG. 7) derives an estimated
procedure time (t) (in min), which predicts the collection time
before the donor is connected. To derive the estimated procedure
time t, the utility function F6 requires the operator to input the
desired yield Yld.sub.GoaL and desired plasma collection volume
PPP.sub.GoaL, and further requires the donor weight Wgt, platelet
pre-count Plt.sub.Pre, and hematocrit H.sub.b or a default estimate
of it. If the operator wants recommended platelet storage
parameters, the utility function requires MPV as an input.
[0246] The utility function F6 derives the estimated procedure time
t as follows: 31 t = - b + b 2 - 4 ac 2 a Eq (32)
[0247] where: 32 a = H eq - H b ( 1 - H b ) EqQb CIR Eq (33) b = (
H eq - H b - H b EqQb CIR ) PPP ( 1 - H b ) 2 - H Eq PV Eq (34) c =
[ PV - PPP ( 1 - H b ) 2 ] H b PPP ( 1 - H b ) Eq (35)
[0248] and where:
[0249] H.sub.eq is a linearized expression of the RBC hematocrit
H.sub.RBC, as follows:
H.sub.eq=0.9489-.lambda.H.sub.bEqQb.sub.CIR Eq (36)
[0250] where:
[0251] H.sub.b is the donor's anticoagulated hematocrit, actual or
default estimation.
[0252] EqQb.sub.CIR is the maximum a-symptomatic equivalent blood
flow rate calculated according to Eq (30).
[0253] and 33 = 61,463 2 Eq (37)
[0254] where:
[0255] .OMEGA. is the rotation speed of the processing chamber
(rpm).
[0256] and where:
[0257] PPP is the desired volume of plasma to be collected
(ml).
[0258] PV is the partial processed volume, which is that volume
that would need to be processed if the overall separation
efficiency .eta..sub.PLt was 100%, derived as follows: 34 PV =
ClrVol Anc .times. 2 ndSep .times. ACDil Eq (38)
[0259] where:
[0260] ACDil is the anticoagulant dilution factor (Eq (2)).
[0261] ClrVol is the cleared volume, derived as: 35 ClrVol =
100,000 .times. DonVol .times. Yld [ DonVol - Prime - ACD Est 3 +
PPP 2 ] .times. Plt Pre - 50,000 .times. Yld Spleen Eq (39)
[0262] where:
[0263] Yld is the desired platelet yield.
[0264] DonVol is the donor's blood volume=1024+51 Wgt (ml).
[0265] Prime is the blood side priming volume of the system
(ml).
[0266] ACD.sub.Est is the estimated anticoagulant volume to be used
(ml).
[0267] Plt.sub.Pre is the donor's platelet count before processing,
or a default estimation of it.
[0268] Spleen is the is the splenic mobilization factor calculated
using Eq (16) based upon Plt.sub.Pre.
[0269] The function F6 also derives the volume of whole blood
needed to be processed to obtain the desired Yld.sub.GoaL. This
processing volume, WBVol, is expressed as follows: 36 WBVol = t
.times. EqQb CIR .times. PPP GOAL ( 1 - H b ) + WB RES
[0270] where:
[0271] t is the estimated procedure time derived according to
Eq(32).
[0272] H.sub.b is the donor's anticoagulated hematocrit, actual or
default estimation.
[0273] EqQb.sub.CIR is the maximum a-symptomatic equivalent blood
flow rate calculated according to Eq (30).
[0274] PPP.sub.GOAL is the desired plasma collection volume.
[0275] WB.sub.RES is the residual volume of whole blood left in the
system after processing, which is a known system variable and
depends upon the priming volume of the system.
[0276] Various features of the inventions are set forth in the
following claims.
* * * * *