MULTIPLE BLOOD BAG SYSTEM

SYSTEME DE SACS DE SANG

English Abstract

ABSTRACT OF THE INVENTION
A multiple blood bag system for storage of blood and
processing of blood into its components is disclosed comprising a
donor bag and one or more satellite bags connected by flexible
tubing. The donor bag is made of conventional PVC plasticized with
di-2-ethylhexyl phthalate and is suitable for long term storage of
whole blood or red cells. The satellite bag or bags is made of a
material which is free of di-2-ethylhexyl phthalate so that this
plasticizer, which is extracted by blood or plasma, will not contaminate
blood components processed or stored in the satellite bags. A
preferred material for a satellite bag and particularly desirable for
storage of platelets is a PVC formulation which contains a trioctyl
trimellitate as plasticizer.

Claims

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. The multiple blood bag system which
comprises a first bag, a second bag, and conduit means
providing sealed flow communication between said first bag
and second bay in which said first bay is made of a plastic
material which comprises a different polymer entity from
that of said second bag, one of said bags being equipped
with a blood collection tube, and the first bay and second
bag exhibit differing physical characteristics which are
selectively beneficial to their functions, and the polymer
entity of the first bag exhibiting the characteristic of
suppressing hemolysis of blood cells on long term storage,
said second bag comprising a transfer bag being made of a
translucent, flexible, sterilizable material which is free
of blood-extractable plasticizers and exhibits a higher
carbon dioxide diffusion characteristic than the other bags
in the system whereby the pH of the platelets stored
therein is resistant to reduction.


2. In a multiple blood bag system which
comprises a first bag, a second bag, and conduit means
providing sealed flow communication between said first and
second bags, the improvement comprising: said first bag
being made of a translucent, flexible, sterilizable
material and containing sufficient di-2-ethylhexyl
phthalate as plasticizer so as to suppress hemolysis of
blood cells on long term storage therein; said second bag
being made of a polyvinyl chloride formulation which
contains a trioctyl trimellitate as plasticizer, said
second bag being translucent, flexible, sterilizable, and
suitable for maintaining the viability of platelets stored
therein for at least three days.






3. The multiple blood bag system of claim 2,
where said trioctyl trimellitate is selected from the group
consisting of tri-isooctyl trimellitate and tri-2-ethyl-
hexyl trimellitate.


4. The multiple blood bag system of claim 3 in
which the amount of tri-isooctyl or tri-2-ethylhexyl
trimellitate present is about 30 to about 50 percent by
weight.


5. The multiple blood bag system of claim 4
wherein the amount of tri-isooctyl or tri-2-ethylhexyl
trimellitate present is about 37 percent by weight.


6. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said second container is intended to receive a
blood component from said first container, and wherein said
second physical characteristic imparted by said second
container material is beneficial to the storage of said
blood component, and said second physical characteristic
includes improved gas transmission characteristics for
improved platelet survival.







7. A multiple blood bag system of claim 6,
wherein said first physical characteristic imparted by said
first container material includes the suppression of
hemolysis of red cells during long term storage.


8. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said first container material includes a blood-
extractable plasticizer, and said second container material
includes a plasticizer other than said blood-extractable
plasticizer in said first container material.


9. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said first physical characteristic imparted by
said first container material includes the suppression of






hemolysis of red cells during long term storage, said first
container material includes a blood-extractable
plasticizer, and said second container material includes a
plasticizer other than said blood-extractable plasticizer
in said first container material.


10. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said second container is intended to receive a
blood component from said first container, and wherein said
second physical characteristic imparted by said second
container material is beneficial to the storage of said
blood component, said first container material includes a
blood-extractable plasticizer, and said second container
material includes a plasticizer other than said blood-
extractable plasticizer in said first container material.


11. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic



and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said material of said second container includes
a polyolefin or a polyester or a polyurethane or a
polyvinyl chloride plastic essentially free of a
blood-extractable plasticizer.

12. A multiple blood bag system of claim 11,
wherein said first physical characteristic imparted by said
first container material includes the suppression of
hemolysis of red cells during long term storage.

13. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said second container is intended to receive a
blood component from said first container, and wherein said
second physical characteristic imparted by said second
container material is beneficial to the storage of said
blood component, and said material of said second container
includes a polyolefin or a polyester or a polyurethane or a
polyvinyl chloride plastic essentially free of a
blood-extractable plasticizer.


11


14. A multiple blood bag system of claim 11, 12,
or 13, wherein said polyvinyl chloride material of said
second container is plasticized with tri-2-ethylhexyl
trimellitate.


15. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, said second container is intended to receive a
blood component from said first container, and wherein said
second physical characteristic imparted by said second
container material is beneficial to the storage of said
blood component, and said second physical characteristic
imparted by said material of said second container includes
a relatively high carbon dioxide diffusion characteristic,
whereby the pH of platelets stored in said second container
is resistant to reduction.


16. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic

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and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, wherein said first physical characteristic
imparted by said first container material includes the
suppression of hemolysis of red cells during long term
storage, said second container is intended to receive a
blood component from said first container, and wherein said
second physical characteristic imparted by said second
container material is beneficial to the storage of said
blood component, and said second physical characteristic
imparted by said material of said second container includes
a relatively high carbon dioxide diffusion characteristic,
whereby the pH of platelets stored in said second container
is resistant to reduction.


17. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication between said first container and said second
container, wherein a plurality of second containers are in
communication through said conduit means with said first
container, and at least one of said second containers
includes a material which exhibits a higher carbon dioxide
diffusion characteristic than the material of any other one
of said containers.
13




18. A multiple blood bag system comprising: a
first container intended to receive blood from a donor, at
least a portion of which container includes a material
which imparts a predetermined first physical characteristic
which is beneficial to the storage of blood in said first
container, a second container including a material which
imparts a predetermined second physical characteristic
which is different than said first physical characteristic
and which is beneficial to the intended function of said
second container, and conduit means providing sealed flow
communication bteween said first container and said second
container, wherein said first physical characteristic
imparted by said first container material includes the
suppression of hemolysis of red cells during long term
storage, wherein a plurality of second containers are in
communication through said conduit means with said first
container, and at least one of said second containers
includes a material which exhibits a higher carbon dioxide
diffusion characteristic than the material of any other one
of said containers.


19. A multiple blood bay system of claim 11 or
13 wherein said material of said second container includes
a polyolefin.


20. A multiple blood bag system of claim 11 or
13 wherein said material of said second container includes
a polyester.


21. A multiple blood bag system of claim 11 or
13 wherein said material of said second container includes
a polyurethane.

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22. A mutliple blood bag system of claim 11 or
13 wherein said material of said second container includes
a polyvinyl chloride plastic essentially free of a blood
extractable plasticizer.

Description

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This invention relates to multiple blood bag systems for
collecting and processing blood under sterile conditions.
For a number of years, blood has been collected and processed
into various components such as packed red cells, plasma platelets and
cryoprecipitate, using a system comprising two or more plastic bags
interconnected by tubing. The blood is first collected from a donor
into a primary or donor bag to which is connected one or more secondary
or satellite bags. Both the donor and satellite bags have been
routinely made of polyvinyl chloride (PVC) film containing as
plasticizer di-2-ethylhexyl phthalate (DEHP). Such a film composi-
tion is currently the only government approved material for blood
bags in a multiple bag system.
For some time, however, it has been known that considerable
amounts of DEHP are leached from the walls of the blood bags by the
plasma in the blood when blood or packed red cells are stored for
long periods of time. There has been concern over the potentially
harmful effects of DEHP on patients repeatedly infused with blood or
blood components even though there appears to be no significant
toxicity based on animal studies.
Consequently, numerous plastic formulations have been tested
in an attempt to find acceptable material for blood bags which would
be flexible, translucent, steam sterilizable and substantially free
of leachable plasticizers. The material should also have properties
which are not detrimental to the components of blood; for example,
the material should not cause undue hemolysis of red cells or decrease
the viability of platelets upon storage to levels which would be
clinically unacceptable.
It was shown very early that the commercially available
blood bags which were made of PVC plasticized with DEHP, were
generally better than glass containers for the long term storage
of blood. Strumia et al (J. Lab. and Clin. Med. 46, 225, 1955)
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demonstrated the hemolysis was less and post transfusion survival of
red cells was improved for blood stored in these plastic bags. This
inherent property of PVC bags plasticized with DEHP has contributed
to this being the only material for blood bags which was and still is
acceptable and approved by Government regulatory agencies. It has
been theorized that this condition of decreased hemolysis of red
cells is attributable to the DEHP which is extracted from the bag
by the blood and that the DEHP inhibits hemolysis.
The present invention concerns a multiple blood bag system
which combines the known advantageous features of presently used
blood bags with respect to minimizing hemolysis of red blood cells
and yet provides a system wherein some of the other blood components
may be processed or stored with essentially no contamination with
blood-extractable plasticizers.
The multiple blood bag system of the invention comprises a
first bag, a second bag, and conduit means providing sealed flow
communication between said first bag and second bag in which said
first bag is made of a plastic material which comprises a difFerent
polymer entity from that of said second bag.
Advantageously, one of said bags is equipped with a blood
collection tube. The first bag and second bag exhibit differing
physical characteristics which are selectively beneficial to their
functions. Suitably, the polymer entity of the first bag exhibits
the characteristic of suppressing hemolysis of blood cells on long
term storage. Suitably, the second bag comprises a transfer bag
being made of a translucent, flexible, sterilizable material which
is free of blood-extractable plasticizers and exhib-its a higher
carbon dioxide diffusion characteristic than the other bags in the
system whereby the pH of the platelets stored therein is resistant
to reduction.

3L'~3~

The physical characteristics of the second bag suitably
include improved gas transmission characteristics for improved
platelet survival.
In a particular further embodiment the -First bag is made of
a translucent, flexible, sterilizable material and containing su-fficient
di-2-ethylhexyl phthalate as plasticizer so as to suppress hemolysis
of blood cells on long term storage therein; and the second bag is
made of a polyvinyl chloride formulation which contains a trioctyl
trimellitate as plasticizer, said second bag being translucent,
flexible, sterilizable, and suitable for maintaining the viability
of platelets stored therein for at least three days.
In a further particular embodiment the invention provides
a multiple blood bag system comprising a first container intended to
receive blood from a donor, at least a portion of which container
includes a material which imparts a predetermined first physical
characteristic which is beneficial to the storage of blood in said
first container, a second container including a material which
imparts a predetermined second physical characteristic which is
different than said first physical characteristic and which is
beneficial to the intended function of said second contai.ner,-and
conduit means providing sealed flow communication between said first
container and said second container; the second physical characteris-
tic particularly includes improved gas transmission characteristics
for improved platelet survival. Generally, the second physical
characteristic imparted by the second container material is beneficial
to the storage of the blood component.
The second container material particularly includes a
plasticizer other than a blood-extractable plasticizer employed in
the first container material. In a particular embodiment the
material of the second container may include a polyolefin or a
polyester, or may be a vinyl chloride plastic essentially free of

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a blood-extractable plasticizer and in particular plasticized with a
trioctyl trimellitate.
In a further particular embodiment there may be a plurality
of second containers in communication through the conduit means with
the first container, at least one of the second containers including
a material which exhibits a higher carbon dioxide diffusion charac-
teristic than the material of any other one of the containers.
The invention is illustrated in an especially preferred
embodiment by reference to the accompanying drawing in which figure
1 illustrates schematically a multiple blood bag system of the
invention.
With further reference to Figure 1, a multiple blood bag
system 10 has a donor bag 12 joined to one or more satellite bags,
in this case two satellite bags 18 and 20, by flexible tubiny 22
and a Y-connector 24. The donor and satellite bags may have one or
more access ports 16 and donor bag 12 is equipped with a blood
collection tube 14 leading to a donor needle (not shown). Fluid
flow through tubing 22 from bag 12 is controlled by any conventional
valving means 26.
The donor bag 12 was made from a conventional PVC formula-
tion which contained about 28 percent by weight of DEHP as plasticizer.
It is contemplated that other PVC formulations could be used in which
the DEHP content could vary between about 20 and about 40 percent by
weight and provide donor bags suitable for their intended use. Both
satellite bags were made from a PVC formulation which contained about
37 percent by weight of a trioctyl trimellitate as plasticizer. It is
also contemplated that satellite bags made from PVC containing from
about 30 to about 50 percent by weight of a trioctyl trimellitate
would also be suitable for their intended use. As examples of
acceptable isomers of the octyl moiety of this class of trimellitate
esters, tri-isooctyl and tri-2-ethylhexyl trimellitate in PVC


formulations have been used. These satellite bags were Flexible,
steam-sterilizable, transparent and substantially none of the
plasticizer was extracted by blood stored therein for up to 21 days
at about 5C. The PVC formulation which contains the trimellitate ester
is suitable for maintaining the viability of platelets stored therein
for at least three days. This was in sharp contrast to the donor
bags where large amounts of DEHP plasticizer was extracted into blood
stored therein under the same conditions. The amount of hemolysis
of red blood cells in blood stored in the satellite bags was somewhat
higher than that for blood stored in the donor bags.
As an example of how the multiple blood bag system of the
invention was used, blood was collected from a donor into the donor
bag of the type specifically described above which contained CPD
anticoagulant solution. Following centrifugation, the valving means
was actuated and the plasma was expressed into one of the satellite
bags (of the type described above, i.e., the PVC formulation contain-
ing about 37 percent of tri-isooctyl trimellitate) where it was further
centrifuged at an appropriate speed to cause the platelets to separate
from the plasma. The platelet poor plasma was expressed into the
second satellite bag and the platelets in about 50 ml. of plasma were
gently agitated in the first satellite bag for three days. It was
demonstrated that the arnount of viable platelets remaining at the end
of this period was as good as that For platelets stored for the same
period of time in PVC-DEHP plasticized bags of the type described for
the donor bags.
In addition to PVC plasticized with a trioctyl trimellitate,
bags were also made from certain polyesters, polyurethanes and poly-
olefins such as polybutylene which would be suitable as satellite
bags.

o

The above has been presented for a further understanding
of the invention and is not intended to limit the invention which is
fully defined by the claims which follow.




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