A flexible, collapsible blood bag which defines an access port
at one end thereof. The blood bag contains cellophane film of sufficient
area to process blood or plasma placed in the bag, so that reinfusion
of the blood to a normal donor, after an appropriate residence time
in the bag, causes a transient increase in the neutrophil count
of the donor's blood. The cellophane film in the bag is folded in
an ordered manner, to define generally parallel flow channels having
ends positioned adjacent the access port. A screen member may be
positioned between the cellophane film and the access port to prevent
blocking thereof by the cellophane film. Also, the cellophane film
may define a large plurality of raised surface portions, relative
to the normal plane of the film, to facilitate the spacing of adjacent,
folded layers of the film from each other. This facilitates the
definition of the flow channels for blood distribution throughout
the cellophane film.
That which is claimed is:
1. The method of manufacturing a blood bag which has an access
port and contains folded cellophane film, which comprises impressing
into said cellophane film large numbers of raised surface creases
relative to the normal plane of said film by transversely constricting
said film relative to the longitudinal axis of said film to form
longitudinal creases, and thereafter allowing said film to re-expand
to its normal transverse width; folding said cellophane film strip
to define a plurality of overlying panels connected together by
fold areas, to define a plurality of parallel flow channels between
said channels; and sealing said folded cellophane film into a blood
bag whereby the cellophane film is retained in folded condition.
2. The method of claim 1 which includes the step of placing a screen
member adjacent one end of said folded cellophane film between said
one end of the cellophane film and said access port.
3. The method of manufacturing a blood bag which contains folded
cellophane film, which comprises, impressing into said cellophane
film a large number of raised surface creases relative to the normal
plane of said film by exposing said film to sufficient heat to cause
it to shrivel; folding said cellophane film strip to define a plurality
of overlying panels connected together by fold areas, to define
a plurality of parllel flow channels between said channels; and
sealing said folded cellophane film into a blood bag whereby the
cellophane film is retained in folded condition.
BACKGROUND OF THE INVENTION
As reported by Brubaker, et al. in the Journal of Laboratory and
Clinical Medicine Vol, 87 No. 6 pages 1075 to 1086 (June 9 1976),
it may be desired to monitor the capability of a patient, particularly
patients undergoing cancer chemotherapy, to release neutrophil blood
cells to the bloodstream from bone marrow.
While various tests for this capability presently exist, the cited
article discloses a recently-developed test, in which a unit of
blood is exposed to the cellophane found in a hemodialysis coil
for about fifteen minutes, in conjunction with heparin, and is then
reinfused to the patient. The result of this is an abrupt drop in
the neutrophil count of the blood, followed within about an hour
by a rapid, transient increase in the blood neutrophil count to
greater than normal.
This rapid and transient increase in the neutrophil count in the
blood is a normal response. Accordingly, patients which fail to
show such an increase in the neutrophil count upon such treatment
indicate that their neutrophil marrow reserve is inadequate.
In Clinical Research, Volume 21 page 56 (1973) an abstract by
Woodward and Brubaker is found reporting the use of a specially-made
Fenwal brand blood bag containing 0.3 square meter of dialysis coil
cellophane in 2250 U.S.P. units of heparin. Stagnation of a unit
of animal blood in this bag for fifteen minutes, and the return
thereof to the animal, resulted in a transient reduction in the
neutrophil count in the blood, followed by an overshoot neutrophilia.
The cellophane-containing blood bag reported in this article was
made simply by stuffing, in a generally random manner, the required
amount of dialysis coil cellophane (typically Cuprophane, sold by
Enka Glanzstoff in Wuppertal, West Germany).
Upon evaluation of these bags, they were found to be unsuitable
for human use, because the blood tended to foam excessively as the
bags were gently kneaded to obtain good contact between the cellophane
and the blood. Also, ai bubbles were trapped in the cellophane,
resulting in an undesirable contact between the blood and air.
DESCRIPITON OF THE INVENTION
In accordance with this invention, an improved blood or plasma
bag containing cellophane for use in the test of neutrophil marrow
reserves is provided.
A flexible, collapsible blood bag which defines at least one access
port at one end thereof contains cellophane film of sufficient area
to process blood filling the bag, so that reinfusion of the blood
to a normal donor after an appropriate length of time, such as fifteen
minutes, causes a transient increase in the neutrophil count of
It has also been found that blood plasma may, if desired, be used
in place of blood in accordance with this invention, to achieve
similar results. As used herein, the term "blood" is intended
to also include cell-free plasma as an equivalent substitute.
The cellophane film in the bag is folded in an ordered manner to
define a plurality of generally parallel flow channels, one end
of the flow channels being positioned adjacent the access port,
to permit the dispersion of blood throughout the cellophane film
without foaming and entrapment of bubbles, and permitting the easy
removal of essentially all of the blood therefrom for reinfusion.
In accordance with this invention, a screen member is positioned
between the cellophane film and the access port, to prevent blocking
of the access port by the cellophane film.
Also, the cellophane film may define a large plurality of raised
surface portions relative to the normal plane of the film, to facilitate
the spacing of adjacent, folded layers of the film from each other,
for the improved definition of the flow channels for blood distribution
throughout the cellophane film.
While generally at least 0.3 square meter of cellophane film is
present in the bag, it is usually preferred for from 0.5 to 3 square
meters of cellophane film to be present in the blood bag, when the
bag is of a size for processing at least one unit of blood.
The screen member described above may be made of a blood-compatible
plastic material and, being a screen member, is of course highly
permeable to the flow of fluid therethrough. The screen member preferably
defines a U-shaped cross section, and encloses the end of the folded,
cellophane film which is adjacent the access port.
The large number of raised portions may be impressed into the cellophane
film in any desired manner, for example by constricting and drawing
the film as a strip through an orifice, for example, a circular
orifice having a radius of about 0.093 inch when using a strip of
cellophane four inches wide. This results in the impression of a
number of longitudinal creases in the cellophane which, when the
cellophane is reopened, serves to provide the slightly-raised surface
portions relative to the normal plane of the cellophane film, which
prevent adjacent panels of the folded, cellophane film in the blood
bag from sticking together so that blood cannot penetrate between
the two panels.
In the alternative, cellophane may be heated at a temperature which
is slightly below the decomposition temperature of the cellophane,
which causes it to shrivel, resulting in another type of slightly
raised surface portions, for the purpose of facilitating the spacing
of adjacent, folded layers of the cellophane film from each other
so that flow channels for blood are made more available.
Referring to the drawings,
FIG. 1 is a plan view of a blood bag of this invention, with portions
broken away for clarity of disclosure.
FIG. 2 is a transverse sectional view taken along line 2--2 of
FIG. 3 is an enlarged, perspective view of the screen member and
the folded cellophane film which is carried inside a blood bag in
accordance with this invention, with a portion broken away for clarity
FIG. 4 is a plan view of a disposable neutrophil test system, including
the bag of FIGS. 1 and 3.
Referring to the drawings, blood or plasma bag 10 is made from
a pair of sheets of blood-compatible plastic such as medical grade
polyvinylchloride, polypropylene, or the like, heat sealed at its
periphery 12 to define a closed container. Flow tubing 14 communicates
with bag 10 and is terminated with spike 16 which may be sealed
with an elongated, removable cap 18. Auxiliary access ports 20
may also be provided to the blood bag, being sealed with a sterile
tab seal in a conventional manner.
A folded cellophane strip 22 is sealed in the blood bag. The cellophane
strip may be, for example, about four inches wide and about 24 to
48 feet long, pleated or otherwise folded in one half to one inch
panels 24 to define an accordion or fan-type fold as shown in FIGS.
2 and 3 in which the separate panels 24 are connected together
along fold lines 26 which extend longitudinally along the bag so
that their respective ends are positioned adjacent the access ports
Accordingly, flow channels 30 32 are defined by the pleated structure
of cellophane in a longitudinal direction along the bag having ends
34 which are correspondingly adjacent to the access ports 14 20.
Hence, blood may be distributed between the access ports and essentially
the entire area of the cellophane 22 via flow channels 30 32. Air
may be expelled from the bag by the same route while it is filling
with blood. The air bubbles are easily removed from the bag, and
blood may also be completely expelled for reinfusion back to the
patient when that is desired.
In this manner, essentially all of the surface area of the cellophane
24 is exposed to the blood.
Alternatively, other folding patterns for the cellophane may be
used, such as a sprial fold pattern. Cuprophane brand cellophane
is the generally preferred type for use.
Normally, when bag 10 is empty, the cellophane 22 will tend to
be flattened from the idealized configuration shown in FIGS. 2 and
3 the various pleated panels overlying each other in a collapsed
form. However, when the bag is filled with blood the cellophane
tends to assume the pleated configuration which is illustrated herein.
The number of pleats in the drawings have been reduced from that
which may be actually used, for simplicity of disclosure. In fact,
it is contemplated that about 192 pleats (i.e. pairs of panels 24)
may be utilizied per bag in the case, for example, of a 4 inch strip
of cellophane which is about 24 feet long (i.e. an area of about
8 sqaure feet or 3/4 square meter), each panel 24 being 3/4 inch
In accordance with this invention, a screen member 36 is provided
which may be made of Saran (poly(vinylchloridevinylidene chloride))
or an equivalent material, being about 43/4 inches wide and 4 inches
long. This screening material may be folded along a line parallel
to its wider dimension to provide a pair of sections 38 40 which
may be about 2 inches wide, or slightly less, connected together
at an area of folding 42 to provde a receptacle of U-shaped cross
section for the pleated cellophane, as specifically shown in FIG.
3. This prevents the cellophane from clogging the access ports 14
20 and restricting flow communication in and out of the bag 10.
Cellophane strip 22 may also define a large plurality of slightly
raised surface portions, specifically shown to be wrinkles 48 extending
transversely to fold lines 26. Wrinkles 48 may be formed, as stated
before, by drawing the strips through a constricted orifice or the
like. In the alternative, the cellophane may have been heated at
a temperature below its decomposition temperature to cause the material
Wrinkles 48 or other surface discontinuities provide sufficient
irregularity between adjacent panels 24 of the cellophane so that
panels 24 tend not to stick together tightly, blocking the entry
of blood between them.
Accordingly, essentially all of both sides of the area of the cellophane
22 can be made available to the access of blood, flowing through
channels 30 32 to and from the cellophane, for treatment of the
After collection in bag 10 and a desired induction period, the
blood can be reinfused to the patient, and the neutrophil content
of the blood monitored as a test of neutrophil marrow reserves.
FIG. 4 shows a typical multiple bag system, utilizing bag 10 for
use in the neutrophil marrow test. Bag 10 is shown as a separate
unit, but, alternatively, it may be integrally joined with the remaining
components of the set. The following is a description of the multiple
bag set of FIG. 4 along with a discussion of how it may be used.
A triple-lead blood-solution recipient set 50 (manufactured for
example by the Fenwal Division of Baxter Travenol Laboratories,
Inc.) is shown. Set 50 has leads 52 54 57 each of which carries
a penetrating spike which is sealed in a removable closure. The
spike of lead 52 is opened, and passed through one of the access
ports 20 of bag 10.
Lead 54 may be connected to a source of sterile saline injection
solution. (Not shown). Clamps 56 and 58 on leads 52 and 54 are
Flow tubing 14 is shown to be connected to an access port 60 of
a blood bag 62 which is preferably part of a double bag system,
including blood bag 64 and connecting tubing as shown and described
below. Bag 62 contains an anticoagulent solution such as heparin
to prevent blood clotting. If desired, the multiple bag system may
be a Fenwal Heparin Double Plasmapheresis BLOOD PACK.RTM. unit,
which is commercially available at the present time, or any other
appropriate multiple-bag system.
Clamp 66 of set 50 is also closed to prevent fluid flow therethrough
at the initial stage of operation.
Clamps 56 and 58 are then opened to allow saline solution to pass
through lead 54 into filter chamber 68 and from there through lead
52 into bag 10 until approximately one third of a liter of saline
solution has entered bag 10. Then, clamps 56 58 are again closed.
Bag 10 is kneaded in order to wet the full surface of the cellophane
film with the saline solution, until the film has been completely
softened and rendered pliable. Then, bag 10 is suspended from an
IV pole, by hanger 68 in inverted position.
The spike 69 of set 50 is connected into Y-site 70 of the double-bag
system of bags 62 64. Then, clamps 56 and 66 are opened to allow
the saline solution to drain through lead 52 and set 50 into flow
tubing 72 and into bag 64. Clamp 74 which may be a slide clamp,
seals the flow tubing 76 which communicates with Y-site 70.
Then, the clamps are all closed, and tubing 72 is sealed or clipped
in two spaced places and severed between them, so that bag 64 containing
the saline wash solution, may be removed and discarded without opening
the sterile system.
Lead 52 is also sealed with spaced seals and severed as well, with
the coupling end of lead 52 remaining in position in bag 10 to retain
a sterile seal.
Blood bag 62 is suspended as far as possible below the donor's
arm. The cover of needle 78 is removed, and phlebotomy is accomplished
in a vein of the donor's arm with needle 78. A blood pressure cuff
may be used if desired.
Donor tubing 80 is opened by removal of the conventional bead from
its end 82 and blood is allowed to flow through tube 80 into bag
62 which contains the anticoagulant, with frequent gentle mixing
of the blood and anticoagulant.
After collection, blood may be flushed out of the tube 80 with
saline solution from lead 54 of set 50 by opening clamps 66 and
58 regulating the flow of saline to a slow drip. Also, through
the remaining part of the process, a slow drip of saline may be
administered through needle 78 to maintain its patency.
At this time in the process, the coupler or spike of transfer tubing
14 of bag 10 may then be inserted into an access site 60 of bag
62 as shown in FIG. 4. It may also be inserted at an earlier stage
of the process if desired. Tubing 14 is clamped with a hemostat
or a slide clamp 86 which may now be opened. Bag 62 is inverted
over bag 10 and hung vertically from hanger 90 to allow the heparinized
blood to pass through tubing 14 into bag 10. Tubing 14 may then
be sealed in two places and severed. Bag 10 may then be gently inverted
several times to mix the blood thoroughly into intimate contact
with the cellophane film.
Bag 10 is placed in a protective overwrap, and may be incubated
at an appropriate temperature and time, for example in a 37.degree.
C. water bath for fifteen minutes. During this time, the blood in
the remaining segment of tubing 14 attached to bag 10 is "stripped"
into bag 10 by use of a Fenwal tube stripping device or the like.
Blood from bag 10 is allowed to flow back into the remaining segment
of tube 14 attached to bag 10 after which a portion of the tubing
may be sealed with another spaced seal and severed from bag 10
to obtain a blood sample. The blood sample may then be conventionally
tested for hemolysis, prior to infusion of the blood back to the
After the fifteen minute induction period, bag 10 is removed from
the water bath, and lead 57 of set 50 is connected to the remaining
access port 20 of bag 10. Clamp 58 is closed to stop the saline
flow, and clamps 92 66 and 74 are opened, after suspending bag
10 from an IV pole in inverted position, to reinfuse the blood through
set 50 tubing 84 and needle 78 back to the patient. Infusion should
take approximately 10 minutes.
When the blood has been reinfused, clamp 58 is once again opened
to flush the set with saline, to return the remaining traces of
blood to the patient. Then all clamps are closed, the phlebotomy
needle 78 removed from the patient, and the apparatus disclosed.
Additional blood samples may be drawn from the patient fourteen
minutes after the start of reinfusion, and then gain at 30 45
and 60 minutes after reinfusion. A neutrophil count is made on each
blood sample, to determine the presence or absence of the normal
While the arrangement of FIG. 4 is shown as one method of utilizing
the invention of this application, other arrangements are equally
possible. In particular, it has been determined that it is not necessary
to place whole blood into the cellophane-containing bag of this
invention in order to obtain the overshoot neutrophilia upon reinfusion
to a patient. Blood plasma, after an exposure to cellophane in the
bag of this invention, similar to the exposure conditions described
above, provides a similar effect in a normal, healthy patient.
Accordingly, if desired, the bag of this invention may be utilized
in conjunction with a plasmapherisis set of a type which is conventionally
sold by the Fenwal division of Baxter Travenol Laboratories, Inc.
Also, plasmapherisis apparatus may be appropriately modified as
desired by the addition of an integrally attached bag of this invention.
Specifically, the bag of this invention may be integrally connected
with a companion blood bag which, in turn, is connected to a phlebotomy
needle by donor tubing which carries a Y-site. Blood is then collected
into the companion bag of the bag of this invention, which companion
bag contains an anticoagulant such as heparin, and both the companion
bag and the bag of this invention may be centrifuged to settle the
cells. Thereafter, the plasma may be administered through the connecting
tubing from the companion bag to the bag of this invention, and
the cells reinfused from the companion bag after being suspended
in saline, which can be administered by a conventional blood set
through the Y-site. Then, after separation of the bag of this invention
and an appropriate period of induction, the plasma may be reinfused
to the patient by connection of the bag of this invention with another
lead of the same blood set.
The above has been offered for illustrative purposes only, and
is not intended to limit the invention of this application, which
is as defined in the claims below.