U.S. patent application number 11/064267 was filed with the patent office on 2005-06-30 for systems and methods for on line finishing of cellular blood products like platelets harvested for therapeutic purposes.
Invention is credited to Bischof, Daniel F..
Application Number | 20050139556 11/064267 |
Document ID | / |
Family ID | 24426942 |
Filed Date | 2005-06-30 |
United States Patent
Application |
20050139556 |
Kind Code |
A1 |
Bischof, Daniel F. |
June 30, 2005 |
Systems and methods for on line finishing of cellular blood
products like platelets harvested for therapeutic purposes
Abstract
Blood processing systems and methods establish on line
communication between a container and a source of blood containing
leukocytes and platelets, such as a human donor. The systems and
methods create a centrifugal field between the source of blood and
the container that separates from the blood an unfinished
suspension of platelets having a first physiologic characteristic
different than the desired physiologic characteristic. The systems
and methods pump the unfinished platelet suspension outside the
centrifugal field through a finishing device. The finishing device
changes the first physiologic characteristic to the desired
physiological characteristic, thereby creating the finished
platelet suspension. The systems and methods convey the finished
platelet suspension from the finishing device directly into the
container. The systems and methods function without interrupting
the on line communication between the container and the source of
blood.
Inventors: |
Bischof, Daniel F.;
(McHenry, IL) |
Correspondence
Address: |
BAXTER HEALTHCARE CORPORATION
ONE BAXTER PARKWAY
DF2-2E
DEERFIELD
IL
60015
US
|
Family ID: |
24426942 |
Appl. No.: |
11/064267 |
Filed: |
February 23, 2005 |
Related U.S. Patent Documents
|
|
|
|
|
|
Application
Number |
Filing Date |
Patent Number |
|
|
11064267 |
Feb 23, 2005 |
|
|
|
10430785 |
May 6, 2003 |
|
|
|
6872307 |
|
|
|
|
10430785 |
May 6, 2003 |
|
|
|
10024733 |
Dec 19, 2001 |
|
|
|
10024733 |
Dec 19, 2001 |
|
|
|
09548190 |
Apr 13, 2000 |
|
|
|
6361692 |
|
|
|
|
09548190 |
Apr 13, 2000 |
|
|
|
09223212 |
Dec 30, 1998 |
|
|
|
6051147 |
|
|
|
|
09223212 |
Dec 30, 1998 |
|
|
|
08606189 |
Feb 23, 1996 |
|
|
|
5865785 |
|
|
|
|
Current U.S.
Class: |
210/787 |
Current CPC
Class: |
A61M 2202/0071 20130101;
A61M 2202/0057 20130101; A61M 1/3693 20130101; A61M 2202/0439
20130101; A61M 2202/0427 20130101; A61M 2202/0427 20130101; A61M
1/3696 20140204; A61M 2202/0439 20130101 |
Class at
Publication: |
210/787 |
International
Class: |
B04B 001/00 |
Claims
1. (canceled)
2. An on line blood processing method for obtaining a finished
blood suspension having a desired physiologic characteristic
comprising the steps of (1) establishing on line communication
between a container and a source of blood, (2) creating, without
interrupting the on line communication between the container and
the source, a centrifugal field between the source and the
container that separates from the blood a first blood suspension
having a physiologic characteristic different than the desired
physiologic characteristic, (3) pumping, without interrupting the
on line communication between the container and the source, the
first blood suspension having a physiologic characteristic
different than the desired physiologic characteristic outside the
centrifugal field through a finishing device outside the
centrifugal field under pressure from the centrifugal field,
thereby creating a second blood suspension having a desired
physiologic characteristic thereby creating the finished blood
suspension, and (4) conveying, without interrupting the on line
communication between the container and the source, the second
blood suspension from the finishing device directly into the
container without exposure to the separation forces of the
centrifugal field, (5) the preceding steps (2) to (4) being
conducted without interrupting the on line communication between
the container and the source.
3. A method according to claim 2 wherein the finishing device
comprises a filter media.
Description
RELATED APPLICATIONS
[0001] This application is a continuation of co-pending U.S. patent
application Ser. No. 10/024,733 filed 19 Dec. 2001, which is a
division of U.S. patent application Ser. No. 09/548,190 filed 13
Apr. 2000, which is a division of U.S. patent application Ser. No.
09/223,212 filed 30 Dec. 1998, which is a division of U.S. patent
application Ser. No. 08/606,189 filed 23 Feb. 1996.
FIELD OF THE INVENTION
[0002] The invention generally relates to blood processing systems
and methods. In a more specific sense, the invention relates to
systems and methods for removing leukocytes from blood components
collected for therapeutic purposes.
BACKGROUND OF THE INVENTION
[0003] Today blood collection facilities routinely separate whole
blood into its various therapeutic components, such as red blood
cells, platelets, and plasma.
[0004] One separation technique that is in widespread use today
uses a multiple blood bag system. The bag system includes a primary
blood bag and one or more transfer bags, which are integrally
connected to the primary bag by tubing. The technique collects from
a donor a single unit (about 450 ml) of whole blood in the primary
blood bag. The donor is then free to leave.
[0005] The donor's whole blood later undergoes centrifugal
separation within the primary bag into red blood cells and plasma
rich in platelets. The plasma rich in platelets is expressed out of
the primary bag into a transfer bag, leaving the red blood cells
behind. The plasma rich in platelets then undergoes further
centrifugal separation within the transfer bag into a concentration
of platelets and plasma poor in platelets. The plasma poor in
platelets is expressed from the transfer bag into another transfer
bag, leaving the concentration of platelets behind.
[0006] Using multiple blood bag systems, all three major components
of whole blood can be collected for therapeutic use. However, the
yield for each component collected is limited to the volume of the
components that are contained in a single unit of whole blood.
Furthermore, because red blood cells are retained, United States
governmental regulations prohibit collecting another unit of whole
blood from the donor until six weeks later.
[0007] Certain therapies transfuse large volumes of a single blood
component. For example, some patients undergoing chemotherapy
require the transfusion of large numbers of platelets on a routine
basis. Multiple blood bag systems simply are not an efficient way
to collect these large numbers of platelets from individual
donors.
[0008] 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.
[0009] 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.
[0010] Regardless of the separation technique used, when collecting
blood components for transfusion, it is desirable to minimize the
presence of impurities or other materials that may cause undesired
side effects in the recipient. For example, because of possible
febrile reactions, it is generally considered desirable to
transfuse red blood cells and platelets that are substantially free
of leukocytes, particularly for recipients who undergo frequent
transfusions.
[0011] Several U.S. patents are directed to the removal of
leukocytes from red blood cells and platelet components in multiple
blood bag systems. For example, see U.S. Pat. Nos. 4,767,541;
5,089,146; 5,100,564; and 5,128,048.
[0012] U.S. Pat. No. 5,427,695 is directed to the removal of
leukocytes from platelet-rich plasma during on line blood
processing.
[0013] The platelet-rich suspension product obtained using prior on
line blood collection systems and methods may still lack the
desired physiologic characteristics imposed by the end user
(typically a blood bank or hospital) for long term storage and
transfusion. For example, the platelet-rich suspension may include
residual leukocytes that, while very small in relation to the
leukocyte population in whole blood, are still greater than the
leukocyte population standards desired by the end user.
[0014] Therefore, despite significant advances in blood processing
technology, a need still exists for further improved systems and
methods for removing undesired matter like leukocytes from blood
components in a way that lends itself to use in high volume, on
line blood collection environments.
SUMMARY OF THE INVENTION
[0015] The invention provides on line blood processing systems and
methods for obtaining a finished platelet suspension having a
desired physiologic characteristic. In a preferred embodiment, the
desired physiologic characteristic comprises a desired reduced
residual population of leukocytes.
[0016] The systems and methods that embody features of the
invention establish on line communication between a container and a
source of blood containing leukocytes and platelets, such as a
human donor. The systems and methods create a centrifugal field
between the source of blood and the container. The centrifugal
field separates from the blood an unfinished suspension of
platelets having a first physiologic characteristic different than
the desired physiologic characteristic. In a preferred embodiment,
the unfinished platelet suspension contains an initial leukocyte
population greater than the desired residual leukocyte
population.
[0017] According to the invention, the systems and methods pump the
unfinished platelet suspension outside the centrifugal field
through a finishing device. The finishing device changes the first
physiologic characteristic to the desired physiological
characteristic, thereby creating the finished platelet suspension.
In a preferred embodiment, the finishing device reduces the
leukocyte population by filtration. The systems and methods convey
the finished platelet suspension from the finishing device directly
into the container for storage or transfusion.
[0018] The systems and methods that embody the features of the
invention function without interrupting the on line communication
between the container and the source of blood.
[0019] Other features and advantages of the invention can be found
in the drawings, accompanying description, and claims of this
Specification.
BRIEF DESCRIPTION OF THE DRAWINGS
[0020] FIG. 1 is a diagrammatic view of a blood processing system,
which includes a finishing device that embodies the features of the
invention; and
[0021] FIG. 2 is a diagrammatic view of a centrifugal blood
processing system that can be use in association with the finishing
device shown in FIG. 1.
[0022] 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
[0023] FIG. 1 shows in diagrammatic form an on line blood
processing system 10 that embodies features of the invention.
According to the invention, the on line system 10 provides a
finished, high quality platelet-rich blood product (PLT.sub.FIN),
with a significantly reduced residual population of leukocytes
and/or other enhanced physiological properties, suited for long
term storage and transfusion.
[0024] As used in this Specification, the term "on line blood
separation process" refers to a blood separation system or method
that (i) establishes communication between a blood source
(typically, a human blood donor) and an extracorporeal flow path;
(ii) draws a blood volume from the donor into the flow path; and
(iii) maintains communication with the circulatory system of the
donor for at least a portion of the time that the blood volume
undergoes separation within the extracorporeal flow path.
[0025] As used in this Specification, an "on line blood separation
process" can separate the blood volume either in a continuous
manner or in an interrupted manner. However, an "on line blood
separation process" maintains communication between the flow path
and the donor for at least a portion of the time the separation
process occurs within the flow path, regardless of specific timing
or sequencing of the separation process itself.
[0026] As used in this Specification, an "on line blood separation
process" can include external or internal valves or clamps to
interrupt flow within the path to or from the donor. However, in
the context of this Specification, such valves or claims do not
break the communication between the blood donor and the flow path.
Instead, the valves or clamps control fluid flow within the path
while maintaining communication between it and the blood donor.
[0027] The on line system 10 draws whole blood (WB) from a donor
through a phlebotomized tubing flow path 12. WB contains, as its
principal components, red blood cells, platelets, leukocytes, and
plasma. The system 10 adds anticoagulant to the drawn WB and
conveys anticoagulated WB into a centrifugal field 14 for
processing.
[0028] In the centrifugal field 14, the system 10 ultimately
separates anticoagulated WB into two components. The first
component is a red blood cell concentration. It is desirable that
the red blood cell concentration also carry with it a majority of
the leukocyte population (LK) present in the WB. For this reason,
the first component is referred to as RBC.sub.LK+.
[0029] RBC.sub.LK+ is returned to the donor during processing. This
avoids depletion of the donor's red blood cell and leukocyte
populations while high volume yields of platelets are obtained.
[0030] The second component comprises an unfinished platelet-rich
plasma suspension PLT.sub.UN. PLT.sub.UN is considered "unfinished"
because the platelet-rich plasma suspension still lacks the desired
physiologic characteristics imposed by the end user (typically a
blood bank or hospital) for long term storage and transfusion.
Centrifugal processing within the field 14 often cannot provide
these desired characteristics.
[0031] The specific physical makeup of the platelet-rich suspension
comprising PLT.sub.UN can vary. The makeup will largely depend upon
the efficiency of the centrifugal separation process in terms of
the how many platelets are separated (i.e., the platelet yields)
and how much platelet-poor plasma product is withdrawn and not
returned to the donor.
[0032] As used in this Specification, PLT.sub.UN is intended to
encompass any suspension in which platelets are present in
concentrations greater than in whole blood. PLT.sub.UN can comprise
what is commonly referred to as platelet-rich plasma (PRP) or
platelet concentrate (PC), or suspensions of platelets and plasma
lying in between.
[0033] PLT.sub.UN can include, in addition to platelets, other
components or ingredients, depending upon the choice of the end
user. For example, PLT.sub.UN can include essentially only plasma
as the platelet suspension media. Alternatively or in addition to
plasma, PLT.sub.UN can include a specially formulated platelet
storage media to suspend the platelets.
[0034] The structural details of the centrifugation field 14 can
vary and are not essential to the invention. For example, the field
14 can comprise a centrifuge and multiple stage centrifugal
processing chambers of the type shown in Brown U.S. Pat. No.
5,427,695 or Brown U.S. Pat. No. 5,370,802, both of which are
incorporated herein by reference.
[0035] As FIG. 2 shows in diagrammatic form, the multiple stage
processing chambers that Brown '695 and '802 embody separate WB
into RBC and PRP in a first stage separation chamber 16. The
special fluid flow dynamics that occur in the first stage chamber
16 shown in Brown '802 or '695 keep a large majority of leukocytes
out of PRP and with the RBC in the first stage chamber 16 for
return to the donor as RBC.sub.LK+. The special fluid flow dynamics
occurring in the first stage chamber 16 in Brown '802 or Brown '695
also provide a high yield of platelets in the PRP.
[0036] In Brown '802 or '695, PRP is transported from the first
stage chamber 16. A portion is recirculated back to the WB entering
the first stage chamber 16, and the rest is conveyed into a second
stage chamber 18. The PRP is separated in the second stage chamber
18 into PC and platelet-poor plasma (PPP).
[0037] PC retained in the second stage chamber 18 is later
resuspended in a volume of PPP or (optionally) a suitable platelet
storage medium for transfer from the second stage chamber as
PLT.sub.UN. A portion of the PPP is returned to the donor, while
another portion of PPP is retained for use as a recirculation or
keep-open or rinse-back or resuspension media, or for storage for
fractionation or transfusion.
[0038] One reason why PLT.sub.UN can be considered "unfinished" in
the context of the above described system is the presence of
residual leukocytes in the platelet suspension. This residual
population of leukocytes with the platelets, while small, still can
be greater than the leukocyte population standards demanded by the
end user.
[0039] Often, centrifugal processing alone often is not effective
at isolating enough leukocytes from PRP to meet these demands.
Unintended perturbations and secondary flows along the interface
between RBC and plasma, where leukocytes reside, can sweep lighter
leukocyte species away from RBC into the plasma. Other desirable
flow patterns that sweep heavier leukocytes species in the
interface back into the RBC mass can also fail to develop to their
fullest potential. The dynamic processes under which leukocytes are
separated from platelets during centrifugation are complex and
subject to variation from donor to donor.
[0040] Additional steps can be provided to augment the primary
centrifugal separation process to thereby reduce the number of
residual leukocytes present in PLT.sub.UN. For example, as
disclosed in Brown '695, a leukocyte filter 20 can be provided
after the first stage chamber 16 to filter leukocytes from PRP
before entering the second stage chamber 18 for separation into PC
and PPP. The filter 20 is preferably located outside the
centrifugal field 14, being connected by a rotating umbilicus
arrangement 22 of conventional construction. Alternatively, though,
the filter 20 can be located within the centrifugal field 14.
[0041] Alternatively, or in combination with such other ancillary
leukocyte-reduction devices, PLT.sub.UN can be subject to particle
bed separation effects within the centrifugal field 14 to separate
leukocytes from the platelets. Still, the degree of leukocyte
reduction demanded by the user can exceed the capabilities of even
these ancillary steps during the centrifugal separation
process.
[0042] For this reason (see FIG. 1), the system 10 includes an in
line finishing device 24 located outside the centrifugal field 14.
A pump 26 conveys PLT.sub.UN under pressure from the centrifugal
field 14 through the finishing device 24. In FIG. 1, the pump 26 is
shown downstream of the centrifugal field 14. Alternatively, the
pump 26 could be located upstream of the centrifugal field 14,
thereby supplying the requisite machine pressure to convey
PLT.sub.UN from the centrifugal field 14.
[0043] The finishing device 24 serves to affect a desired
alteration in the makeup or physiological of PLT.sub.UN that could
not be effectively achieved in the centrifugal field 14, such as,
for example, a further incremental reduction in the leukocyte
population. The in line finishing device 24 performs its function
on line, while the donor remains connected in communication with
the system 10.
[0044] The output of the finishing device 24 is a finished
platelet-rich suspension(PLT.sub.FIN). PLT.sub.FIN is considered
"finished" because the platelet-rich plasma suspension possesses
the desired physiologic characteristics imposed by the end user for
long term storage and transfusion. In the context of the
illustrated embodiment, the platelet-rich suspension comprising
PLT.sub.FIN, possesses a more-reduced leukocyte population and/or
additional physiological attributes not present in PLT.sub.INI.
[0045] As used in this Specification, the term "reduced" or
"more-reduced" does not denote that all the residual leukocytes
have been removed. The term is intended to more broadly indicate
only that the number of residual leukocytes have been incrementally
reduced by the finishing device 24, compared with the number before
processing by the finishing device.
[0046] Other physiological attributes that the finishing device can
provide include (INSERT . . . )
[0047] The finishing device 24 can accomplish its function by
centrifugation, absorption, columns, chemical, electrical, and
electromagnetic means. In the illustrated and preferred embodiment,
the finishing device 24 comprises a filter that employs a
non-woven, fibrous filter media 28.
[0048] The composition of the filter media 28 can vary. The media
28 comprises fibers that contain nonionic hydrophillic groups and
nitrogen-containing basic functional groups. Fibers of this type
are 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. Filter media
containing these fibers have demonstrated the capacity to remove
leukocytes while holding down the loss of platelets. Alternatively,
the filter media 28 can comprise fibers that have been surface
treated as disclosed in Gsell et al U.S. Pat. No. 5,258,127 to
increase their ability to pass platelets while removing leukocytes.
Gsell et al. U.S. Pat. No. 5,258,127 is also incorporated herein by
reference.
[0049] Furthermore, because the pump 26 is used to convey
PLT.sub.INI through the finishing device 24, the external machine
pressure it creates can be used to overcome passive resistance of
the finishing media 28. Therefore, the finishing media 28 can be
densely packed within the finishing device 24 to achieve maximum
efficiencies.
[0050] The system 10 conveys PLT.sub.FIN to one or more containers
30 suitable for transfusion or long term storage. The container(s)
30 intended to store PLT.sub.FIN can be made of 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). These materials, when compared to
DEHP-plasticized polyvinyl chloride materials, have greater gas
permeability that is beneficial for platelet storage.
[0051] The system 10 shown in FIG. 1 can be readily incorporated
into a continuous single or double needle on line blood processing
systems.
[0052] As used in this Specification, the "on line blood separation
process" differs from a multiple blood bag process. In a multiple
blood bag process, the donor's circulatory system does not remain
in communication with the flow path where separation of the
collected blood volume occurs. In a multiple blood bag system,
after a given blood volume is collected in the primary bag, the
donor's circulatory system is disconnected from the primary bag
before separation occurs within the bag. Also, in a multiple blood
bag system, the separation processes do not occur continuously. The
first stage separation of red blood cells and plasma rich in
platelets and the second stage separation of platelets from plasma
occur at different points in time as separate, discontiguous
steps.
[0053] Various features of the inventions are set forth in the
following claims.
* * * * *