Abstrict A multiple blood bag system comprising a donor bag for receiving
blood from a donor, and one or more transfer bags, communicating
by flexible tubing with the donor bag, for receiving a blood component
from the donor bag. In accordance with this invention, the various
bags may be made of differing materials to provide differing characteristics
to the bags as desired. For example, the transfer bag or bags may
be made of a translucent, flexible, sterilizable material which
is free of blood extractable ester-type plasticizers, and may have
a relatively high carbon dioxide diffusion capacity. The donor bag
may be made of a translucent, flexible, sterilizable material which
contains preferably at least five percent by weight of a specified
ester plasticizer, sufficient to cause a substantial reduction in
plasma hemoglobin produced by blood stored under normal conditions
for 21 days in the donor bag, when compared with blood in a corresponding,
plasticizer-free donor bag stored under equivalent conditions.
Claims That which is claimed is:
1. In a 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 bag in which said first bag 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 polymer entity of the the first
bag exhibiting the characteristic of suppressing hemolysis of blood
cells on long term storage, whereby the first bag and second bag
exhibit differing physical characteristics which are selectively
beneficial to their functions.
2. The multiple bag blood system of claim 1 in which a second transfer
bag is present, 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.
3. The multiple bag system of claim 1 in which said first bag is
a donor bag for receiving whole blood from a donor, said blood collection
tube being connected to the first bag, said second bag comprising
a transfer bag for receiving a blood component from the donor bag.
4. The multiple bag system of claim 1 in which said first bag contains
an amount of liquid plasticizer sufficient to suppress the amount
of plasma hemoglobin produced by blood stored therein, when compared
with a corresponding bag free of said plasticizer.
5. The multiple bag system of claim 1 in which said first bag contains
an amount of an ester-type material which is sufficient to suppress
the amount of plasma hemoglobin produced by blood stored therein,
when compared with a corresponding bag free of said ester-type material.
6. The multiple bag system of claim 1 in which said first bag contains
an ester-type plasticizer in a concentration sufficient to cause
a reduction in the plasma hemoglobin content of blood stored in
said bag for 21 days, when compared with a corresponding bag which
is free of said material.
7. 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 second bag being made of a translucent, flexible, sterilizable
material which is free of blood-extractable plasticizers, said first
bag being made of a translucent, flexible, sterilizable material
which contains an amount of liquid plasticizer selected from the
group consisting of dioctylphthalates and dioctyladipates sufficient
to suppress the amount of plasma hemoglobin produced by blood stored
therein.
8. In a multiple blood bag system which comprises a donor bag for
receiving blood from a donor, at least one transfer bag for receiving
a blood component from said donor bag, and conduit means providing
sealed, flow communication between said donor bag and transfer bag,
the improvement comprising:
said transfer bag being made of a translucent, flexible, sterilizable
material which is free of blood-extractable plasticizers, said donor
bag being made of a translucent, flexible, sterilizable material
which contains from 5 to 50 percent by weight of a di-ester selected
from the group consisting of dioctylphthalates and dioctyladipates.
9. The blood bag system of claim 8 in which said liquid plasticizer
is a diethylhexylphthalate.
10. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising:
said transfer bag being made of a translucent, flexible, sterilizable
material, which is free of blood-extractable plasticizers, said
donor bag being made of a translucent, flexible, sterilizable material
which contains from 5 to 50 percent by weight of a diester selected
from the group consisting of di-2-ethylhexylphthalate and di-2-ethylhexyladipate.
11. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising:
said transfer bag being made of a transparent, flexible, autoclavable
material which is free of blood-extractable plasticizers, said donor
bag being made of a transparent, flexible, autoclavable material
which contains from 15 to 50 percent by weight of di-2-ethylhexylphthalate.
12. The multiple blood bag system of claim 11 in which said transfer
bag is made of a polyolefin material.
13. The multiple blood bag system of claim 12 in which said donor
bag is made of a polyester material.
14. The multiple blood bag system of claim 12 in which said donor
bag is made of a formulation of polyvinyl chloride plasticized with
said di-2-ethylhexyl phthalate.
15. The multiple blood bag system of claim 12 in which said donor
bag contains from 15 to 40 percent by weight of di-2-ethylhexyl
phthalate.
16. The multiple blood bag system of claim 12 in which said conduit
means comprises flexible tubing made of the same translucent, flexible
autoclavable material as the transfer bag.
17. The multiple blood bag system of claim 12 in which a plurality
of transfer bags are present, being in communication through said
conduit means with the donor bag.
18. The multiple blood bag system of claim 12 in which at least
one of said transfer bags is made of a copolymer comprising from
10 to 40 percent by weight of a polyolefin consisting essentially
of propylene units; from 40 to 85 percent by weight of a block copolymer,
having thermoplastic rubber characteristics, consisting essentially
of (1) a central block comprising 50 to 85 percent by weight of
the copolymer molecule, of a rubbery olefin polymer of generally
equal proportions of ethylene and butylene units, and (2) terminal
blocks of polystyrene; and from 0 to 40 percent by weight of a softening
agent selected from the group consisting of polyethylene and poly(ethylene-vinyl
acetate) containing no more than 35 percent by weight of vinyl acetate.
19. The multiple blood bag system of claim 18 in which a second
transfer bag is present which is made of a flexible polyester material,
and said donor bag is made of polyvinyl chloride plasticized with
said di-2-ethylhexylphthalate.
20. The multiple blood bag system of claim 11 in which said transfer
bag is made of a polyolefin material which exhibits a relatively
high low-temperature strength, whereby the bag may be frozen for
collection of cryoprecipitate.
21. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising: said transfer bag being
made of a translucent, flexible, sterilizable polyolefin material
which is free of blood-extractable plasticizers and exhibits a relatively
high carbon dioxide diffusion characteristic whereby the pH of platelets
stored therein is resistent to reduction, said donor bag being made
of a translucent, flexible, sterilizable plastic material which
contains from 15 to 50 percent by weight of a blood-extractable
plasticizer selected from the group consisting of dioctylphthalates
and dioctyladipates.
22. The multiple blood bag system of claim 21 in which said extractable
plasticizer is di-2-ethylhexylphthalate.
23. The multiple blood bag system of claim 22 in which said donor
bag is made of a polyvinyl chloride formulation plasticized with
di-2-ethylhexylphthalate.
24. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising: said transfer bag being
made of a translucent, flexible, sterilizable, polyester material,
free of ester-type blood extractable materials, said donor bag being
made of a translucent, flexible, sterilizable, polyvinyl chloride
plastic material which contains from 5 to 50 percent by weight of
di-2-ethylhexylphthalate.
25. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising: said transfer bag being
made of a translucent, flexible, sterilizable material which is
free of blood-extractable plasticizer, said donor bag being made
of a translucent, flexible, sterilizable plastic material, said
donor bag containing in its interior an insert portion of plastic
material which contains at least 5 percent by weight of a blood-extractable
plasticizer selected from the group consisting of dioctylphthalates
and dioctyladipates.
26. The multiple blood bag system of claim 25 in which 15 to 50
percent by weight of said blood extractable plasticizer is present
in said interior plastic insert.
27. The multiple blood bag system of claim 26 in which the outer
walls of said donor bag are essentially free of blood extractable
plasticizers.
28. The multiple blood bag system of claim 26 in which said interior
plastic insert comprises a polyvinyl chloride formulation containing
a blood-extractable plasticizer.
29. In a multiple blood bag system which comprises a donor bag
for receiving blood from a donor, at least one transfer bag for
receiving a blood component from said donor bag, and conduit means
providing sealed, flow communication between said donor bag and
transfer bag, the improvement comprising:
said transfer bag being made of a translucent, flexible, sterilizable
material which is free of blood-extractable plasticizers, said donor
bag being made of a translucent, flexible, sterilizable material
which contains sufficient amount of an ester material selected from
the group consisting of dioctylphthalates and dioctyladipates to
cause a reduction in the plasma hemoglobin content of blood stored
in said bag for 21 days, when compared with a corresponding bag
which is free of said material.
30. The blood bag system of claim 29 in which said ester material
contains branched octyl radicals.
31. The blood bag system of claim 30 in which said ester material
is di-2-ethylhexylphthalate.
32. The multiple blood bag system of claim 29 in which said transfer
bag is made of a polyolefin material.
33. The multiple blood bag system of claim 32 in which said donor
bag is made of a polyester material.
34. The multiple blood bag system of claim 33 in which said donor
bag is made of a formulation of polyvinyl chloride plasticized with
said di-2-ethylhexylphthalate.
35. The multiple blood bag system of claim 34 in which a plurality
of transfer bags are present, being in communication through said
conduit means with the donor bag.
36. The multiple blood bag system of claim 29 in which at least
one of said transfer bags is made of a copolymer comprising from
10 to 40 percent by weight of a polyolefin consisting essentially
of propylene units; from 40 to 85 percent by weight of a block copolymer,
having thermoplastic rubber characteristics, consisting essentially
of (1), a central block comprising 50 to 85 percent by weight of
a copolymer molecule, of a rubbery olefin polymer of generally equal
proportions of ethylene and butylene units and (2) terminal blocks
of polystyrene; and from 0 to 40 percent by weight of a softening
agent selected of the group consisting of polyethylene and poly(ethylene-vinyl
acetate) containing no more than 35 percent by weight of vinyl acetate.
37. The multiple bag system of claim 36 in which a second transfer
bag is present which is made of a flexible polyester material, and
said donor bag is made of polyvinyl chloride which contains di-2-ethylhexylphthalate.
Description BACKGROUND OF THE INVENTION
Multiple blood bags are commercially available from the Fenwal
Division of Baxter Travenol Laboratories, Inc., for collecting and
processing blood under sterile conditions to obtain various blood
components as may be desired, for example, packed red cells, plasma,
platelets, and cryoprecipitate.
The currently-available blood bags are made of a polyvinyl chloride
formulation, which includes, as an ester-type plasticizer, di-2-ethylhexylphthalate.
This blood bag system has served extremely well in the storage and
processing of blood and blood components, exhibiting a high survival
rate, with a resultingly low plasma hemoglobin content after, for
example, 21 days of storage.
However, some concern has been expressed from various sources about
the potential undesirability of the plasticizer leaching from the
plastic material, and entering the blood, from where it is infused
to the patient upon infusion of the blood or blood components. This
is so despite the lack of any apparent significant toxicity of the
particular plasticizer used, the concern being about long-term and
subtle effects not yet discovered.
Accordingly, various plastic formulations which are flexible, translucent,
sterilizable, and free of liquid plasticizers capable of leaching
have been tested as blood bag materials. Many of the plastic formulations
which have been tested have physical characteristics which are different
from each other and from the current polyvinyl chloride formulations.
For example, some plastic formulations have an improved capacity
to transfer carbon dioxide, so that it would be of advantage to
make one or more of the transfer packs of a multiple blood bag of
such a material to permit an increased diffusion rate of carbon
dioxide through the transfer pack during platelet storage so that
the pH decrease of the platelets during storage is reduced.
It has been surprisingly found that the presence of certain ester-type
plasticizers such as di-2-ethylhexylphthalate and di-2-ethylhexyladipate
in plastics causes a significant lowering of the plasma hemoglobin
content during long-term storage of blood in containers made of
such plastics.
Accordingly, in accordance with this invention, the overall contact
of blood plasma and other components to the blood-extractable plasticizer
may be minimized, while still attaining low plasma hemoglobin levels
in long-term storage, by providing a multiple blood bag system in
which the donor bag is made of a plastic which contains a blood
extractable plasticizer, preferably a branched dioctyl phthalate
ester plasticizer, but the transfer bags are free of blood extractable
plasticizers. Accordingly, the red blood cells, which normally are
retained in the donor bag, are stabilized and preserved by the surprising
benefit which has been found by the presence of the specific plasticizers
described above. At the same time, the plasma and other blood components
may be removed from the donor bag, being thus freed from further
exposure to the plasticizer, and stored in transfer bags of different
materials of different desirable characteristics, for example, transfer
bags made of a material having relatively high carbon dioxide diffusion
capability.
Accordingly, in accordance with this invention, the specific properties
of the various bags of the multiple blood bag of this invention
may be optimized by the use of different materials for each of the
bags as desired, with one bag material being chosen for the donor
bag in order to minimize the formation of plasma hemoglobin and
to maximize the life of the red cells, while the transfer packs
may be made of material having other characteristics, for example,
the relatively high carbon dioxide diffusion capability.
DESCRIPTION OF THE INVENTION
The multiple blood bag system of this invention comprises a donor
bag for receiving blood from a donor, and at least one transfer
bag for receiving a blood component from the donor bag. The donor
bag and transfer bag are connected together by conduit means providing
sealed flow communication between them.
In accordance with this invention, the donor bag and transfer bag
may be made of plastic materials which each comprise a different
polymer entity so that the respective bag materials exhibit different
characteristics which may be specifically selected for beneficial
effect in the specific function of each of the transfer and donor
bags.
For example, the transfer bag or bags may be made of a translucent,
flexible, sterilizable material which is free of blood-extractable
plasticizers. On the other hand, the donor bag may be made of a
transparent, flexible, sterilizable material which contains an amount
of blood-extractable plasticizer selected from the group consisting
of dioctylphthalates and dioctyladipates, preferably di-2-ethylhexylphthalate,
and preferably in a concentration in the flexible material of 5
to 50 weight percent, and typically about 15 to 40 weight percent.
This can result in a substantial reduction in plasma hemoglobin
produced by blood stored under normal conditions for 21 days in
the donor bag, when compared with blood in a corresponding donor
bag, free of blood extractable plasticizers and stored under equivalent
conditions.
If desired, only portions of the bag materials which are in contact
with the blood contained therein may contain the blood-extractable
plasticizers of this invention, although preferably the entire bag
material contains the plasticizer. Alternatively, a plastic insert
member such as a sheet of plastic or the like positioned within
the blood bag may contain the blood-extractable plasticizer material,
while the actual bag walls may be relatively free of plasticizer.
Both of these circumstances are generally equivalent to the preferred
use of blood-extractable plasticizer throughout essentially the
entire material of the donor bag.
It is specifically desirable for the concentration and configuration
of plasticizer in the bag to be such that when the bag is filled
with blood and stored on a long term basis, the concentration of
the blood-extractable plasticizer in the blood rises to typically
about 30 to 100 micrograms per ml., and preferably from about 50
to 80 micrograms of the plasticizer per ml., in the blood in 21
days. This takes place due to the extraction of the plasticizer
from the plastic material in dissolved form into the blood.
It has been found to be difficult to dissolve the blood-extractable
plasticizers used herein in bulk in the blood, and it has been found
that a greater beneficial effect is provided by placing the extractable
plasticizer in the plastic material of the blood bag for extraction
by the blood during the storage period.
The transfer bag or bags and optionally the tubing in the blood
bag of this invention may be made of a polyester material in accordance
with the teachings of U.S. Pat. No. 4045431.
It may also be desirable to make the donor bag of the multiple
bag system of this invention out of a similar polyester material
to the transfer bag, but containing blood-extractable plasticizer.
Alternatively, bags of this invention may be made out of a blood-compatible
polyurethane formulation.
Another type of material which is suitable for the transfer bag
of this invention comprises a mixture of from 10 to 40 percent by
weight of a polyolefin consisting essentially of propylene units;
from 40 to 85 percent by weight of a block copolymer, having thermoplastic
rubber characteristics, consisting essentially of (1) a central
block comprising 50 to 85 percent by weight of the copolymer molecule
of a rubbery olefin polymer (and preferably consisting of generally
equal proportions of ethylene and butylene units); and (2) terminal
blocks of polystyrene; and as a third, optional ingredient, from
0 to 40 percent by weight of a softening agent such as polyethylene
or poly(ethylene-vinyl acetate) containing no more than 35 percent
by weight of vinyl acetate units. This polyolefin formulation exhibits
relatively good low temperature strength and good carbon dioxide
transfer characteristics, and thus is suitable for use as transfer
bags for collecting cryoprecipitate or storing platelets.
The above material is further described in U.S. patent application
Ser. No. 819924 filed July 28 1977 now U.S. Pat. No. 4140162.
The above block copolymer is commercially available from the Shell
Chemical Company under the trademark KRATON or KRATON-G, the latter
class of materials being preferred.
Other materials from which the transfer bags of this invention,
and optionally the tubing, may be made include poly(ethylene-vinyl
acetate) copolymers, and polyethylene formulations, all of the above
material being preferably essentially free of the blood-extractable
plasticizers.
The donor bag, as described above, contains a blood extractable
liquid plasticizer as described above, the plasticizer being generally
present in a concentration of 5 to 50 percent by weight of the overall
plasticized plastic material making up the donor bag.
Preferably, a conventional formulation of polyvinylchloride, plasticized
with a dioctyl phthalate such as di-2-ethylhexylphthalate, similar
to present commercial formulations, may be used. Alternatively,
other plastics such as a polyester bag formulation may be used,
for example utilizing the above-described polyester, in which preferably
from 15 to 40 percent by weight of the di-2-ethylhexylphthalate
plasticizer is present, either by formulation along with the original
plastic material, or by allowing the plastic to soak in the diethylhexylphthalate
until the desired amount of plasticizer has been taken up by the
material. Typically, the polyester formulation may contain about
20 percent by weight of the ester plasticizer.
Alternatively, di-2-ethylhexyladipate or an equivalent material
may be used as the blood-extractable plasticizer.
Referring to the drawings, FIG. 1 is a plan view of a multiple
blood bag system in accordance with this invention.
Blood bag system 10 includes a donor bag 12 which may be of conventional
construction, being made of a pair of plastic sheets, being sealed
at periphery 14 and containing a blood collection tube 16 having
the usual donor needle, and a pair of access ports 18.
Transfer tubing 20 is connected to donor bag 12 for fluid flow
through the transfer tubing, being controlled by conventional valving
means 22 such as a cannula and diaphragm valve. Transfer tubing
20 communicates through Y site 23 to transfer bags 24 26 which
may also be of conventional construction, with the exception of
the materials of which they are made, having the conventional access
ports 28 and other known design features.
In accordance with this invention, transfer bags 24 26 are made
of a material which may be translucent (e.g., transparent), flexible,
and preferably autoclavable to permit sterilization, being made
of a material which is free of blood-extractable plasticizers, for
example, a material as described above. Accordingly, plasma and
other blood components which are expressed into transfer bags 24
26 enter an environment free of additional exposure to plasticizers.
In fact, the plasticizer-free formulations of bags 24 26 can reduce
the plasticizer level in the blood components by absorption thereof
if the blood bag material of the transfer bags is of an appropriately
plasticizer-compatible material.
It is specifically preferable for at least one of the transfer
bags 24 26 to be made of a material which has a relatively high
capability to permit the diffusion of carbon dioxide, so that the
bag may be desirably used as a platelet storage bag. Specifically,
such a bag may be made from the polyolefin-thermoplastic rubber
formulation described above and in the cited U.S. patent application
Ser. No. 819924 filed July 28 1977 or other formulations described
therein. Alternatively, the same transfer bag may be used to collect
and store cryoprecipitate in view of its good low temperature strength.
The other of the two transfer bags may be made of the polyester
formulation described above. Accordingly, one preferred embodiment
the multiple bag shown in the drawings may comprise a pair of transfer
bags 24 26 each of which is made of a different material from
the other. Alternatively, they may be the same.
Tubing 20 may be made of a flexible material, free of blood-extractable
plasticizers, similar to that of one of the transfer bags 24 26
if desired, or it may be made of the material of donor bag 12 or
any other desired material.
Donor bag 12 is made of a transparent, flexible, preferably autoclavable
material which contains the desired amount of blood-extractable
plasticizer as described above, to cause a substantial reduction
in the plasma hemoglobin of blood stored under normal conditions
for 21 days in the donor bag 12 when compared with a corresponding
extractable plasticizer-free donor bag stored under equivalent conditions.
As stated above, a commercial polyvinyl chloride blood bag formulation
may be used, which contains di-2-ethylhexyl phthalate. Alternatively,
another plastic such as a polyester material as described above,
containing the desired amount of compatible liquid plasticizer,
may be used.
If desired, an optional plastic insert 32 may be inserted within
the donor bag 12. Insert 32 may be made of a similar material to
donor bag 12 or a material which is particularly compatible to
the desired blood-extractable plasticizer used herein. Accordingly,
the material of bag 12 may be relatively free of the desired blood-extractable
plasticizer, but insert 32 within the bag may carry any desired
amount of the plasticizer, preferably from 15 to 70 percent by weight,
to provide the extractable plasticizer to the blood which is placed
in bag 12. It has been found that the desirable results of this
invention can be achieved by this alternate technique. Insert 32
may be a single sheet, or a plurality of plastic beads, or any other
convenient structure.
For example, the blood bag may be made out of a polyolefin such
as polyethylene, polypropylene, the polyolefin block copolymer formulation
described previously, polyester, polyurethane, or any other blood-compatible,
inert, flexible plastic material. Insert 32 on the other hand,
may be made of a blood-compatible polyvinyl chloride formulation
and may contain most preferably up to about 50 percent of di-2-ethylhexylphthalate
or di-2-ethylhexyladipate, to be extracted into the blood over the
storage period. If desired, higher concentrations than 50 percent
of the extractable plasticizer may be used in insert 32 since there
is no need for insert 32 to exhibit a high tensile strength, as
would be necessary if it were part of the bag wall itself. Correspondingly,
the specific bag material chosen for use may be free of the extractable
plasticizer, while the advantages of this invention are still achieved.
Accordingly, as blood is collected through the donor tube 16 into
the blood bag 12 mixing with blood preservative 30 such as ACD
or CPD solution in bag 12 the blood may then be processed or stored
as desired. During storage, the presence of the plasticizer effectively
suppresses the amount of plasma hemoglobin which is generated over
a period of time, compared with blood stored in a bag made of a
formulation which is free of blood-extractable plasticizers.
The blood may be centrifuged, with the red cells settling to the
bottom of donor bag 12 and the plasma and other components being
expressed through tubing 20 into transfer bags 24 26. Thereafter,
the expressed blood components are free from exposure to plasticizer,
while the red cells in bag 12 may be stored with appropriate treatment
to continue to receive the benefit of the presence of plasticizer
in the material of transfer bag 12.
The materials from which transfer bags 24 26 are made may also
exhibit other benefits; for example, polyolefins and other materials
may have improved gas transmission characteristics for improved
platelet survival, since the carbon dioxide diffuses through the
bag wall more readily than with polyvinyl chloride, with the result
that the pH remains more stable.
Also, if desired, donor bag 12 and transfer bags 24 26 may be
separate bags that have been connected together during use by means
of a sterile connector system, for example, that shown in U.S. Pat.
No. 4004586 or any other sterile connector system.
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