Abstrict A bag for the separation of components in blood by gravitational
settlement or centrifugation, has an upper chamber and a lower chamber
connected by a slender neck, there being access conduits to each
of said chambers and said neck. The bag is so dimensioned that for
blood having a normal hematocrit the interfaces between packed red
cells and the buffy coat and between the buffy coat and the plasma
will lie within the neck. The neck can then be clamped off or otherwise
sealed to separate the phases sharply and to permit virtually 100%
recovery of the plasma and the packed red cells. In a second embodiment,
the buffy coat can be isolated and seals within the system opened
to permit intermixing of the plasma and the packed red blood cells
under completely sterile conditions. A special support makes it
possible for the blood bag to be subjected without distortion to
centrifugation.
Claims What is claimed is:
1. A blood bag in combination with a rigid support means, said
blood bag of flexible, at least translucent plastic for separation
of whole blood into fractions and for direct transfusion therefrom,
said bag comprising an upper chamber, a lower chamber, a sealable
neck of reduced cross section connecting said upper and lower chambers,
said upper and lower chambers and neck cooperating to define a gap
when said blood bag is filled with blood, said rigid support means
having a shape which generally conforms to the contour of said gap,
said support means when positioned in said gap functioning to prevent
collapse of said upper chamber toward said lower chamber during
centrifugation, means for introducing blood into said blood bag
and means for removing fractions of said blood subsequent to separating
same, whether by gravity or by centrifugation, said upper and lower
chambers and said neck being so sized that when separation of blood
of normal range hematocrit into packed red blood cells, buffy coat
and plasma is carried out in said bag, the interfaces between said
packed red blood cells and said buffy coat and between said buffy
coat and said plasma will lie in said neck, said plastic being of
a flexibility such that application of pressure to either one of
said chambers will move said interfaces toward the other chamber,
thereby providing for positioning both of said interfaces within
said sealable neck prior to sealing same.
2. The blood bag as defined in claim 1 wherein said neck is adapted
for sealing by clamping.
3. The blood bag as defined in claim 1 wherein said blood bag
is of a heat-sealable material.
4. The blood bag as defined in claim 1 wherein the volumes of
said neck, said lower chamber and said upper chamber are respectively
about 5%, 38% and at least approximately 57% of the total volume
of blood to be fractionated.
5. The blood bag as defined in claim 1 wherein said upper chamber
has a bottom and said lower chamber has a top, said bottom sloping
downwardly toward said neck and said top sloping upwardly toward
said neck.
6. The blood bag as defined in claim 1 wherein said means for
introducing blood into said bag includes a sealable tube.
7. The blood bag as defined in claim 6 wherein said sealable tube
is connected to said upper chamber.
8. The blood bag as defined in claim 1 wherein said means for
removing fractions includes at least one tube connected to each
of said chambers and to said neck, each of said tubes being pierceably
sealed, whereby plasma, buffy coat and platelets and packed red
cells may be selectively removed from said blood bag subsequent
to separation and occlusion of said neck above and below said buffy
coat.
9. The blood bag as defined in claim 1 wherein said support means
is shaped to conform to said bottom of said upper chamber and said
top of said lower chamber.
10. The blood bag as defined in claim 1 wherein said upper and
lower chambers and neck are rectangular in cross section.
11. A method of separating whole blood into recoverable fractions,
comprising the steps of filling with blood a flexible, at least
translucent bag having upper and lower chambers connected by a neck
with a gap between said chambers, positioning rigid support means
in said gap between said chambers, said upper and lower chambers
being sized so that on settling, buffy coat will lie within said
neck with blood of normal hematocrit, centrifuging said bag with
support means causing packed red cells to separate from said blood,
exerting pressure on one of said chambers where necessary to bring
the upper surface of said packed red blood cells into said neck
and near the bottom thereof, and sealing said neck immediately below
said upper surface, thereby making it possible to recover virtually
100% of said packed red blood cells from the blood in said bag.
12. The method of separating whole blood into recoverable fractions
as defined in claim 11 further comprising the step of causing the
buffy coat to separate from said blood, the volume of said neck
being more than adequate to hold said buffy coat, and sealing said
neck immediately above said buffy coat, thereby making it possible
to recover virtually 100% of said plasma free of said buffy coat
and of packed red cells.
13. The method of separating whole blood into recoverable fractions
as defined in claim 12 wherein said separation is effected by gravitational
settling.
14. The method of separating whole blood into recoverable fractions
as defined in claim 12 wherein said separation is effected by differential
centrifugation.
15. The method of separating whole blood into recoverable fractions
as defined in claim 14 further comprising the step of placing a
support means between said upper and lower chambers prior to centrifugation
to hold said chambers apart during centrifugation.
16. The method of separating whole blood into recoverable fractions
as defined in claim 12 wherein said bag has a second neck connecting
said upper and lower chambers, said second neck being openably sealed
at the top and bottom thereof prior to separation of any blood components
and further comprising the steps of opening said seals subsequent
to sealing off said neck containing said buffy coat and mixing said
packed red cells and said plasma under sterile conditions by causing
said packed red cells and plasma to flow alternately from one chamber
to the other through said second neck for subsequent transfusion
as whole blood less leucocytes and platelets.
17. The method of separating whole blood into recoverable fractions
as defined in claim 12 wherein said blood bag has a second neck
connecting said upper and lower chambers filled with a non-deleterious
liquid to prevent rupture of a seal due to unbalanced forces during
centrifugation.
18. The method of separating whole blood into recoverable fractions
as defined in claim 12 further comprising the steps of removing
said buffy coat from said bag, and separating the platelets from
said buffy coat for administration to a platelet-deficient patient.
19. The method of separating whole blood into recoverable fractions
as defined in claim 11 further comprising the step of placing a
support means between said upper and lower chambers prior to centrifugation
to hold said chambers apart during centrifugation.
20. The method of separating whole blood into recoverable fractions
as defined in claim 11 further comprising the step of washing said
packed red blood cells within said bag in preparation for transfusion
of said red blood cells.
21. A blood bag of flexible, at least translucent plastic for separation
of whole blood into fractions and for direct transfusion therefrom,
said bag comprising an upper chamber, a lower chamber, a sealable
first neck of reduced cross section connecting said upper and lower
chambers, a second neck connecting said chambers, means for introducing
blood into said blood bag and means for removing fractions of said
blood subsequent to separating same, whether by gravity or by centrifugation,
said upper and lower chambers and said first neck being so sized
that when separation of blood of normal range hematocrit into packed
red blood cells, buffy coat and plasma is carried out in said bag,
the interfaces between said buffy coat and said plasma will lie
in said first neck, said second neck initially having seals at the
top and bottom thereof, and containing therein, means to open said
seals, said second neck functioning upon the opening of said seals
to mix plasma with red blood cells within said bag after separating
same, said plastic being of a flexibility such that application
of pressure to either one of said chambers will move said interfaces
toward the other chamber, thereby providing for positioning both
of said interfaces within said sealable first neck prior to sealing
same.
Description BACKGROUND OF THE INVENTION
Conventional storage of whole blood is accompanied by the accumulation
of microaggregates in blood which are thought to be harmful when
transfused (pulmonary microembolism). This particulate matter derives
principally from dead or disintegrating white blood cells and platelets
which have a much shorter life (3 to 5 days) than oxygen-carrying
red cells. Non-viable platelets and leucocytes are unnecessary in
the context of stored-blood transfusion. Current transfusion practice
relies upon microfiltration of this debris between the container
and the patient during the process of transfusion for removal of
this solid matter. This is a moderately expensive and imprecise
procedure. Moreover, failure to remove this debris completely can
have serious consequences.
As an example of such consequences, febrile reactions and sensitivity
to transfused blood are frequently related to transfused white blood
cells or platelets which are non-functional after storage. Current
methodology for their total removal from transfused blood is time-consuming,
relatively costly and cumbersome and wasteful of up to 25% of the
red cell mass.
A further point to be considered is that not all patients require
whole blood transfusion. Many patients specifically require only
plasma, red cells, white cells or platelets. Hence, fractions from
any given unit ideally should be capable of serving more than one
patient if necessary. Although current component methodology for
this purpose is relatively well-defined, separation of components
is usually irreversible once it is performed.
A number of attempts have been made to overcome the difficulties
described above, one such attempt being described by W. C. James
in U.S. Pat. No. 3513976.
James shows two rigid flasks, each having a conical end, the conical
ends being joined by a neck. The objective of this device is similar
to that of subject invention, namely a device which can be subjected
to settling in order to establish interfaces which lie within the
neck; adjustment can be made by adding mercury to the bottom flask
through a tube or by removing mercury originally present from the
bottom flask. The separated white cells or plasma can then be removed
through a pipette. Clearly, this is an undesirable method because
of inevitable admixture during pipetting, breach of sterile technique
in blood handling and the obvious hazards of mercury contact. Although
not so stated in the patent, it is evident that James' flasks are
rigid; at column 2 line 50 it is stated that the device may be
made of glass or any other material having the required property
of transparency. This description could include a transparent plastic
film, but the entire description reads in general on a rigid structure.
G. R. Ryan in U.S. Pat. No. 3761408 shows a flexible plastic
bag in a transfusion apparatus. In his FIG. 9 the bag is shown separated
into two portions by clamps, so that plasma and cells can be withdrawn
separately. In addition, in column 3 line 5 and 6 Ryan states
that heat sealing may be used instead of the clamps. (1) However,
white blood cells and platelets cannot be immediately and aseptically
segregated or removed from blood; (2) blood components cannot be
either stored in or transfused directly from individual parent chambers
to patient; (3) the option for component or whole blood therapy
cannot be maintained throughout the period of blood storage and
(4) the capacity for in-container washing is not afforded.
As is evident, although the concept of a plastic bag for use in
the separation of whole blood has been disclosed and the concept
of a design which facilitates separation of the components has also
been disclosed, although with respect to rigid apparatus, it would
be highly desirable that there be made available a plastic bag which
is low in cost and which can be subjected to centrifugation to facilitate
separation of various components. Moreover, the design of the bag
should be such as to make it possible to recover virtually the entire
quantities of red blood cells in the original volume of blood. Further,
the design should be such that any of the components can be taken
off separately, the components referred to being plasma, buffy coat
with platelets, and packed red cells, and that, where desired, red
blood cells in combination with plasma can be obtained. Finally,
the design should be such that microfiltration for the purpose of
removal of debris from the separated products should not be necessary.
SUMMARY OF THE INVENTION
A blood bag for the separation of blood into plasma, buffy coat,
with platelets (the combination hereinafter referred to as "buffy
coat") and red blood cells, is made of flexible, transparent
plastic, the bag consisting essentially of upper and lower chambers
connected by a neck. Each of the chambers and the neck has sealed
conduits attached thereto for the purposes of filling the bag with
blood and for removing components after separation, access for performance
of these steps being had by means of hypodermic needles which pierce
the seals. The chambers are sized relative to each other and the
neck is so sized that after separation is effected, the buffy coat
will lie entirely within the neck, but with some margin. If the
interfaces between the phases do not lie entirely within the neck,
adjustments can be made by applying pressure to the appropriate
chamber. The neck can then be sealed off above and below the buffy
coat, making all three phases readily available. It is especially
significant that the plasma and the red blood cells are uncontaminated
with the buffy coat or other debris resulting from decomposition
of same.
A special support makes it possible to centrifuge the bag, the
support holding the chambers apart during centrifugation.
In a second embodiment, after sealing off the buffy coat within
the neck, a second neck can be opened to connect the upper and lower
chambers and thus permit intermixing of the plasma with the red
blood cells, where such a mixture is desired for transfusion.
The second neck is sealed off during the separation process, and
special means are provided for opening the seals subsequent to sealing
off the buffy coat within the first neck. A safety clip is provided
for preventing accidental opening of the seals in the second neck
during manipulation and centrifugation.
Separation is effected either by gravity settlement or by centrifugation.
Separation by centrifugation is preferred due to its rapidity. Further,
if differential centifugation is carried out starting at a relatively
low velocity, two interfaces result, these being the boundary between
the packed red cells and the buffy coat and between the buffy coat
and the platelet-rich plasma. Where only the packed red cells are
required, the procedure can be stopped at this point. To separate
the platelets from the plasma, the centrifugation is carried out
at high velocity and the platelets separate downwardly from the
plasma.
Formation of the interfaces is facilitated by the shape of the
chambers, the bottom of the upper chamber and the top of the lower
chamber sloping toward each other at the first neck.
Accordingly, an object of the present invention is a blood bag
for separating the components of the whole blood, namely, plasma,
buffy coat and red blood cells, the bag being shaped so that it
is convenient to isolate the buffy coat from the other components,
thereby making it possible to obtain both plasma and packed red
blood cells free of buffy coat components.
Another object of the present invention is a blood bag which can
separate whole blood into its components and afford practically
100% utilization of the plasma and red blood cells thus obtained.
A further object of the present invention is a blood bag which can
be subjected to centrifugation for the purpose of separating whole
blood into its components.
An important object of the present invention is a blood bag in
which the components of whole blood can be separated from each other
with efficiency high enough so that microfiltration for the purpose
of removing buffy coat components immediately prior to transfusion
is unnecessary.
An important object of the present invention is a method of separating
blood into its components through the use of an appropriately shaped
blood bag. f
A significant object of the present invention is a method of separating
packed red blood cells from whole blood where the packed red cells
are completely free of buffy coat components and plasma, such a
separation being desired when only the packed red blood cells are
needed.
Still other objects and advantages of the invention will in part
be obvious and will in part be apparent from the specification.
The invention accordingly comprises the several steps and the relation
of one or more of such steps with respect to each of the others,
and the apparatus embodying features of construction, combination
of elements and arrangements of parts which are adapted to effect
such steps, all as exemplified in the following detailed disclosure,
and the scope of the invention will be indicated in the claims.
BRIEF DESCRIPTION OF THE DRAWING
For a fuller understanding of the invention, reference is had to
the following description taken in connection with the accompanying
drawings, in which:
FIG. 1 is a view in perspective of a blood bag in accordance with
the present invention;
FIG. 2 is a front view of a second embodiment of the invention;
FIG. 3 is a view in enlarged scale along line 3--3 of FIG. 2; and
FIG. 4 is a view in perspective of a support for use in combination
with the blood bag of FIG. 1.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A device in accordance with the present invention is indicated
generally in FIG. 1 by the reference numeral 21 the device being
a flexible transparent bag divided into upper and lower chambers
1 and 2 connected by a narrow vertical section or neck 3. Chamber
1 has a conventional donor tube or port 1a, transfusion, access
ports 1b and 1c and hanger 1d. Chamber 2 has conventional transfusion
and access ports 2a and 2b. All donor transfusion and access ports
are sealed or sealable, such seals being effected by appropriate
caps, plastic discs, or by knotting of donor tube 1a.
Neck 3 is open, allowing free communication between chambers 1
and 2. This neck is of such a shape that it can be sealed off by
clamping (or heat or ultrasound) proximate to its upper and lower
ends. The chambers are so sized that when blood is collected in
the bag and allowed to settle or centrifuge, the interfaces between
plasma, buffy coat and red cells will lie within the open neck 3.
In the event that the levels of these interfaces do not fall within
the neck (e.g., abnormal hematocrit) the level may be adjusted by
application of pressure to the appropriate end of the bag. The pressure
may be applied manually or by a roller, etc. Following sedimentation
of the fractions or slow centrifugation within the container, followed
by any necessary adjustment of the interfaces, the red cell mass
may be isolated from the buffy coat and plasma by occlusion across
the lower end of the neck making certain that the separation is
within the red cell mass so that no buffy coat is included in the
red cell phase. Following this procedure by rapid centrifugation
results in the sedimentation of both platelets and leucocytes within
neck 3 these being the components of the buffy coat. The upper
end of the neck may then be occluded and both ends of neck 3 heat-sealed,
making certain that the upper sedimentation line is within the plasma
phase, thus effecting a permanent exclusion of platelet and leucocyte
material responsible for white body reaction and particulate matter
in bank blood.
Sharp separation of the blood into the three components is facilitated
by the fact that bottom 4 of the upper chamber 1 slopes downwardly
toward neck 3 whereas top 6 of the bottom chamber 2 slopes upwardly
toward neck 3; in other words, surfaces 4 and 2 slope toward each
other as they approach neck 3. It can readily be seen that sloping
surface 4 provides a funnel effect for guiding particulate matter
such as the buffy coat and the red cells into neck 3. Upwardly sloping
surface 6 provides a similar function, during adjustment of the
interfaces in the event of an abnormal hematocrit, in which case
one or both interfaces may lie within chamber 2 in this case, chamber
2 is compressed and sloping surface 6 guides one or both interfaces,
as the case may be, into neck 3.
Generally, the quantity of blood treated will be a "blood
unit" having a volume of about 450 cc. Conveniently, the volumes
of the neck and lower chamber will be about 5% and 38% of this value,
with the upper chamber having a volume of at least 57% of this value.
Since the hematocrit of normal blood lies between 35% and 45% and
is generally close to 40%, the two interfaces will usually fall
within neck 3. If one or both interfaces are outside neck 3 they
can be displaced into neck 3 by pressure applied to the appropriate
chamber. Neck 3 can then be sealed off proximate to its upper and
lower ends 7 and 8 respectively. Since the sealing-off process
takes place at regions which are outside the limits of the buffy
coat, no part of the undesired solid matter can remain in either
the plasma or the packed red blood cell fractions. Subsequently,
microfiltration between the blood bag and the recipient during transfusion
is unnecessary. If desired, the buffy coat can be removed through
tube 9.
To prevent collapse of chamber 1 toward chamber 2 during centrifugation,
block 11 is positioned in the gap between chambers 1 and 2 during
centrifugation. The block 11 can have an aperture 12 therein to
receive tube 9. Conveniently, block 11 can be made of a rigid plastic
such as polymethylmethacrylate, and, conveniently, may be hollow.
Where a second neck such as is shown in FIGS. 2 and 3 is present,
block 11 may be appropriately notched (not shown).
An important feature of the design is that throughout the storage
life of the blood, the option for whole blood transfusion or specific
component administration remains open. In fact, after fractionation
and sealing of the neck above and below the buffy coat, the bag
can be cut apart to separate the chambers with their individual
contents. Each chamber can then be used directly for transfusion
therefrom. The packed red cells in the lower chamber can be washed
in the conventional manner, through the ports provided.
Where it is desired to transfuse both the plasma and the red blood
cell fractions, exclusive of the white blood cells and platelets,
of course, then it would be advantageous to be able to recombine
the plasma and red blood cell fractions within the blood bag, and
thus avoid the possibility of loss of sterility. This objective
can be met by introduction of a second neck connecting chambers
1 and 2 as shown in FIGS. 2 and 3. A second neck connecting chambers
1 and 2 is shown in an enlarged sectional view in FIG. 3 wherein
the second neck has the reference numeral 13. In order to prevent
the buffy coat from entering second neck 13 during the separation
process, the upper and lower ends of neck 13 are closed respectively
with seals 14 and 16. After separation is effected, the seals must
be opened. An example of a device for opening the seals is a piercing
means 17 disposed within neck 13 said piercing means 17 having
slots or apertures therethrough, or being sized smaller than said
neck to provide a path for the flow of liquid. The piercing means
17 may be fitted with knives 18 and 19 for penetration of seals
14 and 16 during handling, and, especially during centrifugation,
a support means 22 may be provided, said support means 22 clamping
neck 13 immediately above and below the central portion of piercing
means 17. To provide against displacement of support means 22 during
centrifugation, the bottom end thereof may rest against the top
of lower chamber 2. Further, where there is concern for breakage
of seal 14 due to the centrifugal pressure generated by the fluid
in chamber 1 neck 13 may be filled with a non-deleterious fluid
23 such as normal saline, thereby providing transfer of the pressure
exerted by the fluid in chamber 1 to the fluid in chamber 2.
After the fractionating is complete the buffy coat in neck 3 is
sealed off, support 22 which can be hinged for easy removal, is
separated from neck 13 and piercing means 17 is manipulated by the
fingers until it pierces both seals 14 and 16 in succession. Following
opening of seals 14 and 16 the bag is tipped back and forth so
that fluid will flow back and forth from one chamber to the other,
the process being continued until thorough mixture is effected.
For this purpose, upper chamber 1 may be larger than 57% of the
volume of blood to be treated. Also neck 13 should be of relatively
large diameter and the openings made in seals 14 and 16 should also
be generously sized to facilitate the mixing process. When mixing
is complete, the resultant mixture, which is completely free of
unwanted components can then be transfused directly.
As is evident from the structure of the blood bag disclosed herein,
it is possible to obtain each of the fractions separately or any
pair of the fractions in admixture. Moreover, the buffy coat may
be withdrawn through conduit 9 and treated to separate off the platelets
for administration to platelet-deficient patients. Also, where only
the red blood cells are desired, the separation process can be stopped
at the state where the red blood cells are separated from the other
fractions. Further, and most important, since neck 3 holds, at most,
only five percent of the total volume of the original blood volume,
and sealing of the neck can be effected close to the interfaces,
the recovery of plasma and packed red blood cells can be virtually
100%, instead of the much lower recoveries obtainable with conventional
systems.
In using the blood bag, the bag is prepared by introducing a measured
conventional quantity of energy-rich anti-coagulant. The blood unit
is introduced through tube 1a which is then sealed as by clips,
knot or other conventional means. After carrying out the fractionation
as described above, the selected fraction or combination of fractions
may be transferred directly to a patient without an intervening
filter, the fraction or fractions being withdrawn through the appropriate
outlet provided.
A number of different types of plastics can be used. The plastic
should be at least translucent so that the position of interfaces
is observable. The plastic should also be sealable, for convenience
in fabrication, and so that neck 3 can be sealed off proximate but
beyond the interfaces. The sealing of neck 3 can be effected by
clamping, as aforenoted, by heat or by sonic means.
It will thus be seen that the objects set forth above, among those
made apparent from the preceding description, are efficiently attained
and, since certain changes may be made in carrying out the above
method and in the construction set forth without departing from
the spirit and scope of the invention, it is intended that all matter
contained in the above description and shown in the accompanying
drawings shall be interpreted as illustrative and not in a limiting
sense.
It is also to be understood that the following claims are intended
to cover all of the generic and specific features of the invention
herein described, and all statements of the scope of the invention
which, as a matter of language, might be said to fall therebetween. |