Symposium Section

 

The Plasma Bank

MICHAEL DEBAKEY, M.D-*
New Ortgans, LOvIsIANA

NTIL relatively recently the terms

“blood bank” and “plasma bank”
would have baffled the most learned lexi-
cographer. Their current wide adoption
even by laymen not only implies their
ready acceptance and thorough compre-
hension but also indicates the intensive de-
velopment of this subject within a few
years. The terms are not merely meta-
phoric, but essentially descriptive. The
basic principles of the operation of a blood
or plasma bank are similar to those of a
business bank. One cannot withdraw
money from a bank without having pre-
viously made a sufficient deposit or bor-
row money without having made provi-
sions for repayment. Similarly in a blood
bank the deposition of blood must precede
withdrawal and a loan must be repaid, for
obviously depletion without replenishment
would soon cause bankruptcy or cessation
of the blood bank’s function.

Whereas the idea of a blood or plasma
bank is not new, its practical realization is
relatively recent. Over 70 years ago var-
ious investigators were studying the value
of plasma and serum in perfusion experi-
ments. Indeed the procedure of transfu-
sion of stored blood was suggested as early
as 1875 by Freer. This investigator, on
the basis of experimental investigations in
which dogs were transfused with blood that
had been preserved in the refrigerator for
72 hours, stated that: “The practical value
of a knowledge of these facts we believe to
be of great importance, in relation to the
operation of blood transfusion, for this
knowledge removed apprehension concern-
ing the integrity of the blood, when trans-
fusing, leisurely, which is essential to suc-
cessful avoidance of distressing, if not
dangerous, symptoms; also it renders it
possible to save up blood for future use,
the convenience of which must be appar-

ent—.” In 1907, Gutherie and Pike
showed experimentally that plasma and
serum were effective in the treatment of
hemorrhage and subsequently a number of
investigators confirmed these observations.
In 1914, Abel and his co-workers envision-
ed the possibilities of the storage of blood
for emergency use. During the last Great
War, Ward, recognizing the difficulties of
whole blood transfusion in emergencies,
Suggested the use of plasma. Similarly
Rous and Wilson directed attention to the
advantages of plasma in such cases. In
1916, Rous and Turner demonstrated the
practicability of transfusing conserved
blood and two years later Robertson pub-
lished an account of its application in the
United States Army Medical Service. How-
ever, for some curious reason, these prom-
ising developments lagged for over a dec-
ade and then, with the presentation by
the Russian workers of their investigations
on stored blood and cadaver blood trans-
fusion, fresh impetus was given to the
study. In this country probably the first
“blood bank” was developed at Cook
County Hospital. Since then extensive
experimental and clinical investigations
have been reported, clearly establishing the
practical value of stored blood and plasma
in the treatment of hemorrhage, shock,
burns and hypoproteinemia.

As previously emphasized, there are a
number of practical advantages to the use
of blood plasma over whole blood. In
transfusing whole blood it is necessary to
obtain a suitable donor, which requires
compatibility and serologic tests. These
are time-consuming procedures which in
emergencies may be significant. Moreover,
the availability of donors is an important
factor to consider, especially in military
practice in which therapeutic measures
must be instituted under adverse circum-

*From the Department of Surgery, School of Medicine, Tulane University, and the Section on Surgery,

Ochsner Clinic, New Orleans, Louisiana.

311
312

stances and in which expediency is an ab-
solute necessity. These difficulties can be
readily obviated by the use of plasma.
By adequate preparation, large quantities
of plasma may be provided in advance and
safely stored for long periods without de-
terioration and be ready for instant use.
Preliminary typing and compatibility tests
are unnecessary because iso-agglutinins are
partially suppressed by pooling and fur-
ther inhibited by the patient’s blood.
Plasma can also be readily transported by
various means of conveyance without the
inconvenience of refrigeration and admin-
istered with the simplicity and facility of
ordinary saline solution.

Aside from these technical advantages,
extensive clinical and experimental inves-
tigations have clearly demonstrated that
plasma is not only a satisfactory substi-
tute for whole blood in the treatment of
most conditions, but in some cases is dis-
tinctly superior. It is now well establish-
ed that diminished circulating blood vol-
ume is one of the most significant features
in peripheral circulatory failure or shock
due to hemorrhage, trauma, or burns. In
hematogenic shock the decrease in circu-
lating blood volume is due to the loss of
whole blood but in other types of shock,
such as “wound shock” or that consequent
to trauma and burns, it is due primarily
to loss of blood plasma. Accordingly, the
rational treatment of such conditions is
based upon an attempt to produce a
prompt return to normal of the circulating
blood volume and to maintain it at this
level. The most effective means of accom-
plishing this is by the intravenous admin-
istration of a fluid similar in constituency
to blood. This is due to the fact that in
such states as described above there is a
depletion of plasma proteins which are es-
sential in maintaining osmotic pressure
and therefore in holding fluids in the vas-
cular tree and attracting them from the
tissues. Accordingly, the addition of non-
colloidal solutions, such as isotonic salt
solution or glucose solution, merely di-
lutes the plasma proteins, with consequent
diminution of the osmotic pressure, result-
ing in a greater and more rapid escape of
fluid from the vessels which is further en-
hanced by the increased permeability due
to capillary damage by anoxia. Thus, it
becomes obvious that no other substance

INTERNATIONAL MEDICAL DIGEST

can act as efficaciously as blood in sub-
stantially increasing and maintaining cir-
culating blood volume in the presence of
a previously depleted vascular system.
Because of certain inherent disadvantages
in the use of whole blood, various attempts
have been made to use a substitute fluid
more readily available. With the excep-
tion of plasma or serum which, strictly
speaking, cannot be considered substitute
fluids because they contain practically all
the fluid elements of whole blood, none of
the substitutes has proved wholly satis-
factory.

As previously stated, in many conditions
plasma is not only just as effective thera-
peutically as whole blood but in some is
even more rational. Thus, in peripheral
circulatory failure due to local trauma or
visceral exposure and in burns, there is
“plasma loss” and usually hemoconcentra-
tion. In such states the diminution in
blood volume is more effectively corrected
by the transfusion of plasma rather than
whole blood, because the addition of red
blood cells is not only unnecessary, but
theoretically might be harmful. On the
other hand, because in severe hemorrhage
the cellular as well as the fluid element is
lost, the transfusion of whole blood would
appear more rational. Under such cir-
cumstances, the loss of red blood cells may
embarrass the oxygen-carrying capacity
of the circulating blood. Accordingly, the
transfusion of whole blood not only sup-
plements the circulating blood volume but
replenishes its oxygen-carrying capacity.
While this is undoubtedly true, it should
be realized that even in hematogenic shock
the transfusion of plasma is also beneficial
and effective because in such a condition
the most pressing need is the restoration of
circulating blood volume.

Increase in circulating blood is not the
only rationale for plasma transfusion. As
previously emphasized, blood transfusion
may be considered essentially as replace-
ment therapy and in this respect plasma is
just as efficacious as whole blood in most
conditions. Perhaps the most prominent
exceptions to this are those states requir-
ing increase in oxygen-carrying capacity.
Thus, whole blood is preferable in severe
hemorrhage or in pronounced acute and
chronic anemias, in certain forms of in-
toxications and poisonings such as carbon
SYMPOSIUM SECTION

monoxide and nitrobenzol poisoning, in
which the hemoglobin combines with the
poison to form a stable compound and thus
loses its oxygen-carrying capacity, and in
certain forms of leukopenia or agranulocy-
tosis. On the other hand, plasma is pref-
erable in shock not due to hemorrhage, in
burns, in nutritional edema associated with
hypoproteinemia but not anemia, in ne-
phritis with edema, in nephrosis, and con-
centrated plasma in cerebral edema. In
most infections fresh whole blood is prob-
ably preferable, although in certain forms
of infections not associated with anemia
properly prepared plasma may be just as
satisfactory. It is considered inexpedient
to attempt here a detailed account of the
various advantages and indications of
plasma and whole blood, respectively, as
such considerations may be found else-
where. According to Strumia and Mc-
Graw, they may be summarized as fol-
lows:
1, Shock: ©

(a) Associated with little or no hemorrhage

—Plasma.

(6) With severe hemorrhage—Plasma for

immediate relief, followed by whole
blood if warranted.

2. Burns:
Plasma. (It should be added that in late
burns accompanied by anemia whole
blood is indicated.)

3. Infections:
(a) For the purpose of supplying specific
and nonspecific immune bodies—Plasma.
(b) Supplement with whole blood in pres-
ence of severe anemia.

4. Hypoproteinemias:
Due to nutritional, hepatic, nephrotic, and
other causes—Plasma.

5. Cerebral edema:
Due to injuries, toxemias, etc.—Plasma.

6. Blood dyscrasias:

(a) Those with hemolytic tendencies, low
prothrombin content, hemophilia, etc.—
Plasma.

(b) Those with hemorrhagic tendencies as
in certain forms of purpura—Whole
blood,

7, Anemias:

As palliative procedure in various hypoplas-
tic forms—Whole blood; plasma in
chronic forms of hypoproteinemic ane-
mias.

8. Acute poisonings:

Affecting the oxygen-carrying capacity of
hemoglobin, such as carbon monoxide
poisoning—Whole blood.

313

Various methods have been proposed in
the preparation and preservation of
plasma. In general they may be classified
into two types: (1) those directed toward
preparing and preserving fresh liquid
plasma; and (2) those directed toward
preparing dried plasma. It is inopportune
to attempt here a detailed discussion of
the advantages and disadvantages of these
various methods. This phase of the sub-
ject has been adequately reviewed in a pre-
vious publication. Strumia and McGraw
have recently considered the best methods
of preparing and preserving plasma and
have directed attention to certain signifi-
cant observations. One of the most com-
mon methods of preserving plasma in the
liquid state consists essentially in keeping
it in the refrigerator at a temperature of
+4° to +6° C. It was soon found that
there were certain objections and even
dangers associated with this method. Be-
cause it is accompanied by progressive
flocculation of the most unstable proteins,
it requires filtration previous to adminis-
tration. The use of such plasma without
previous filtration has caused at least one
reported death. Bacterial contamination
and the development of pyrogenic sub-
stances is another danger associated with
this method of preserving liquid plasma.
Strumia and McGraw empnasize the im-
portance of not relying too much upon the
addition of bacteriostatic substances such
as merthiolate. They recently reported
five severe reactions following the admin-
istration of such plasma. Still another im-
portant objection to this method of plas-
ma preservation is the continuous and pro-
gressive loss of such essential elements as
prothrombin and complement. For these
reasons this method of preparing and pre-
serving plasma is considered undesirable.

On the basis of their extensive investi-
gations Strumia and McGraw have come
to the conclusion that the preservation and
storage of plasma in the frozen state is the
method of choice. The advantages of this
method consist essentially in ease of prep-
aration, economy, ease of storage and of
transportation, retention of the most labile
elements such as prothrombin and comple-
ment, maintenance of sterility, elimination
of flocculation and consequent filtration
before administration, and in not requir-
ing water for restoration in contradistinc-
314

tion to dried plasma. Another advantage
of this method is that dried plasma, which
has certain advantages especially in mili-
tary practice, is best prepared from the
frozen state.

In order to assure these advantages in
the application of this method of plasma
preservation, Strumia and McGraw have
emphasized certain essential technical con-
siderations to which strict adherence is
necessary. These consist briefly in freez-
ing the plasma fairly rapidly, i¢., within
three to six hours; maintaining the frozen
plasma in storage at a definitely safe level
below freezing, -10° C. or below; and
thawing rapidly and warming to room tem-
perature in a water bath at +37° C. with
occasional gentle agitation, the procedure
not requiring more than 25 minutes.

For the reasons stated above only the
method described by Strumia and Mc-
Graw will be considered here. This meth-
od of plasma preparation may be divided
into several parts: (1) collection of blood;
(2) separation, pooling, and distribution
of plasma; (3) freezing and preservation
of plasma. It should be realized that this
is essentially a closed system, permitting
minimal transfers and manipulations.
Strict adherence to an aseptic technique is
further necessary to maintain sterility.

In the collection of blood certain appa-
ratus is necessary. This has been de-
scribed in detail and illustrated in pre-
vious publications, and consists essential-
ly of an 850-cc. pyrex bottle having a
short neck fitted with a hooded rubber
stopper provided with two holes into each
of which is inserted a glass tube (Figs. la
and 15). One of these glass tubes is con-
nected by a small length of rubber tubing
to a mouthpiece with a saliva trap (Fig.
1c) and the other by longer tubing to a
glass needle adapter which is protected by
inserting it in a small test tube (Fig. 1d).
The donor needle is prepared by placing
it in an hourglass container stoppered with
cotton (Fig. le). After assembling these
various parts and placing 50 cc. of 4 per
cent sodium citrate in normal saline solu-
tion in the bottle, the entire apparatus is
sterilized in the autoclave. The appa-
ratus is now ready for the collection of
blood from the donor.

In the selection of a prospective donor,
certain considerations such as age, gen-

INTERNATIONAL MEDICAL DIGEST

eral health, and freedom from communi-
cable disease are important. While the
drinking of several glasses of a nonfatty
fluid is encouraged, the donor should
avoid a meal during the four hours pre-
ceding the bleeding. After selecting a
suitable vein, the area is adequately pre-
pared and draped as in the preparation of
an operative field. Since strict asepsis is
necessary, the operator should also pre-
pare himself as for a surgical operation.
The site and technical considerations of
venipuncture have been previously de-
scribed and illustrated in detail. After
applying the donor needle to the needle
adapter, the venipuncture is performed
and by applying suction to the mouthpiece
a continuous flow into the bottle is assur-
ed. The bottle should be gently rotated
to insure adequate mixture with the anti-
coagulant. After collecting the full
amount (3 cc. per pound of body weight
for females and 3.5 cc. per pound for
males) the tourniquet is released, the do-
nor tube is pinched, and the needle re-
moved from the vein. The glass adapter
from which the donor needle has been re-
moved is then placed in the glass test tube.
By milking the rubber tube, the blood re-
maining in it may be discharged into the
glass tube for subsequent serologic tests.
The two rubber tubes are then slightly
pulled and folded down alongside the neck
of the bottle and fixed tightly with stout
rubber bands, thus effectively sealing the
bottle. Two identification tags, one for
the collecting bottle and the other for the
glass tube containing the blood for typing
and serologic tests, are filled out. The bot-
tle containing blood withdrawn from the
donor should be placed in the refrigerator
at 4° C. as soon as possible after collec-
tion and kept there until used or the plas-
ma is separated.

Obviously this method is readily appli-
cable to the purpose of a blood bank. If
a whole blood transfusion is desired the
procedure consists essentially of removing
the hooded rubber stopper and applying
another provided with a setup for dispens-
ing the blood and consisting essentially of
a rubber stopper having two holes, into
one of which is fitted a long glass tube to
act as an air vent and another shorter
tube which is connected to a length of
tubing having a recipient’s needle at the
end. If the blood is to be used for the
SYMPOSIUM SECTION

preparation of plasma, it is extremely de-
sirable to diminish as much as possible
the time interval between the collection
of blood and the separation and “fixation,”
i.e., the freezing, of plasma. The impor-
tance of this lies in the fact that possible
bacterial growth from even minor contam-
ination is minimized and greater reten-
tion of the most labile elements such as
prothrombin and complement is assured.
In any case it is desirable to store whole
citrated blood not longer than 3 to 5 days
before separation of plasma.

Separation of plasma is effected by cen-
trifugation or sedimentation. The former

is the procedure of choice because it per-
mits a higher yield and the procurement
of fresh plasma which is distinctly supe-
The special centrifuge preferred by

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315

Strumia and McGraw is the No. 3 Inter-
national Centrifuge Model F. S. capable
of maximal speed of 2500 r.p.m. and pro-
vided with a speed regulator and tachom-
eter. Careful attention to the details of
centrifugation is important; these have
been described in previous publications.
After centrifugation it becomes neces-
sary to draw off, pool and distribute the
plasma. The value of pooling lies in the
fact that a more uniform product may be
obtained, dilution of occasional high ag-
glutinin titer is permitted, and bacterio-
logic control study is simplified. In order
to minimize bacterial contamination dur-
ing this process, it is essential that an ab-
solutely closed system be employed. For
practical purposes the size of the pool

 

 

 

 

Figure 1—Component parts of blood-taking bottle as advocated by Strumia and McGraw.
(a) Pyrex bottle containing citrate saline solution and provided with (b) hooded rubber stopper
having two holes fitted with glass tubes, one of which is connected by length of rubber tubing
to (c) mouthpiece with saliva trap, and the other to (d) a glass needle adapter fitted with a
protecting glass test tube to which may be attached (e) the donor needle.
316

must be limited and in the experience of

trumia and McGraw it is satisfactory to
pool 10 individual bleedings averaging
300 cc. each.

The apparatus required for this proce-
dure consists of a 4-liter pooling bottle
provided with a two-holed rubber stop-
per into each of which is fitted a glass
tube (Figs. 2¢ and 25). One of these
glass tubes, which is partially closed at
each end and filled with cotton to form
an air filter (Fig. 2c), is connected to a

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INTERNATIONAL MEDICAL DIGEST

vacuum pump when plasma is drawn into
the bottle and to a pressure pump when
plasma is being distributed in individual
containers. The other tube (Fig. 2d) is
connected on the inside of the bottle to a
longer tube which reaches to the bottom
of the bottle and on the outside of the
bottle to a T tube (Fig. 2e¢), one arm of
which leads to an aspirating cannula for
drawing the plasma (Figs. 2f and 2g),
and the other to the distributing burette
(Figs. 2h and 2i) for distributing the

  
   

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Figure 2,Closed system apparatus for drawing, pooling, and distribution of plasma as advocat-
ed by Strumia and McGraw. (a) The 4-liter pooling bottle is fitted with (b) a rubber stopper
having two holes one of which contains (c) an air filter glass tube and the other (d) another
glass tube which is connected on the inside of the bottle to a longer tube reaching to the bottom
of the bottle, and on the outside to (¢) a T tube, one arm of which leads to (f) an aspirating
cannula for drawing the plasma from (g) the collecting bottle, and the other to (4) a distributing
burette which is connected at the bottom to (i) a specially constructed rubber and glass hooded
cannula for distributing the plasma to (j) the final containers,
SYMPOSIUM SECTION

plasma to the individual containers (Fig.
2j). The cannula used for aspirating the
plasma from the collecting bottles and that
used for distributing the plasma to the
individual containers are protected by
specially constructed rubber sleeves and
glass hoods, the details of which are illus-
trated in Figures 2f and 27. After this ap-
paratus is properly assembled, the screw-
clamps on the tube leading to the distribut-
ing burette and on that leading to the
aspirating cannula are closed and vacuum
created in the pooling bottle by applying
suction. The aspirating cannula (Fig. 2)
is then inserted through the rubber tube
and pulled taut to form a diaphragm over
the opening of the glass tube in the col-
lecting bottle (Fig. 2g) until it reaches
the plasma. An air vent is pushed through
the diaphragm of the other tube to per-
mit replacement by air of the plasma
drawn off. The screw-clamp on the tube
leading from the aspirating cannula is
then released, allowing plasma to be drawn
into the pooling bottle. Aspiration is con-
tinued until only a thin layer remains.
The aspirating cannula is then removed
and the procedure repeated with the next
bottle until the desired number of plas-
mas, approximately 10, have been pooled.
The screw-clamp on the tube leading from
the aspirating cannula is then closed and
the plasma in the pooling bottle is mixed
by gentle rotation. A specimen of the
pooled plasma may be obtained for bacte-
riologic study or other examinations by
applying air pressure to the pooling bot-
tle, inserting the specially constructed dis-
tributing cannula through a perforable
rubber stopper of a culture medium bottle
and releasing the screw-clamp on the tube
leading to the distributing burette. Be-
fore distributing the plasma, 0.1 cc. of 10
per cent merthiolate solution for every
100 cc. of plasma is added by aspirating
the prepared amount into the pooling bot-
tle in a manner similar to that used for
aspirating the plasma from the collecting
bottle. The plasma may then be distrib-
uted to the individual containers by clos-
ing the screw-clamp on the tube leading
to the aspirating cannula and that on the
tube leading from the distributing burette
to the distributing cannula, opening the
screw-clamp leading to the distributing
burette, and applying air pressure to the

317

pooling bottle. As the plasma enters the
burette, the air is displaced through the
filter tube in the stopper and when the de-
sired amount of plasma is obtained the
clamp on the tube leading to the burette
is tightened. The. specially constructed
cannula leading from the burette (Fig. 22)
is inserted through the rubber stopper of
the final container (Fig. 27) and the plas-
ma in the burette allowed to enter it by
opening the clamp on the rubber tube
leading from the burette. It should be
observed that a sterile hypodermic needle
is inserted through the rubber stopper of
the final container to act as an air vent
while the plasma is being introduced. Both
the distributing cannula and hypodermic
needles are removed from the stopper of
the final container after all the plasma in
the burette has entered the final container
and the clamp on the tube leading from
the burette is tightened. This procedure
is repeated for each distribution of plasma.

The plasma which is now in the final
container is ready for storage. As pre-
viously emphasized, it is best preserved in
the frozen state and it is important that
the “fixation” or freezing be done as soon
as possible after the plasma is placed in
the final container. The essential tech-
nical features of this method of preserva-
tion consist of fairly rapid freezing and
maintenance at a fairly low temperature,
-10° C. or below. Various forms of freez-
ing cabinets, most commonly employed for
the storage of ice cream and capable of
maintaining temperatures of -15° C. to
-20° C., may be obtained for this purpose.
The final container of plasma is placed in
such a cabinet in a slanting position so as
to obtain the largest possible surface of
the plasma fluid.

In preparing this frozen plasma for ad-
ministration certain technical steps must
be closely followed. These consist briefly
of rapid thawing in a water bath at 37° C.
After the container of frozen plasma is re-
moved from the freezing cabinet, it is im-
mediately immersed in a water bath at
37° C. and kept there with occasional
gentle rotation and shaking until the plas-
ma has thawed completely, a process usu-
ally requiring about 30 minutes. It is then
allowed to remain in the water bath for
5 or 10 minutes longer to allow it to reach
room temperature. Obviously it is desir-
318

able to administer the plasma as soon as
possible after it has completely thawed.
In this clear state it may be safely admin-
istered without filtration. If the admin-
istration must be delayed for a number of
hours, it should be kept at room tempera-
ture.

In the administration of this plasma it
is desirable to use the same container.
This may be accomplished by employing a
container having a rubber stopper provid-
ed with a long glass tube to act as an air
vent and extending from the stopper to
within a short distance of the bottom of
the bottle. By perforating, with a needle,
the thin rubber membrane covering the
tube an air vent is created. The bottle is
provided with a cloth sling for suspension
in the inverted position. The plasma may

INTERNATIONAL MEDICAL DIGEST

then be administered by inserting through
the rubber stopper a large bore needle
which is connected to a length of rubber
tubing having a glass adapter at the other
end to be fitted to the venipuncture needle.

As previously stated, another advantage
of storing plasma in the frozen state is
that this is the best method of preparing
dried plasma. There are certain distinct
advantages and indications for dried plas-
ma, especially in military practice, as dem-
onstrated by the fact that it is the method
currently employed by the United States
Army and Navy. No attempt will be
made here to describe the technique of
preparing dried plasma as this has been
adequately presented in recent publica-
tions.

BIBLIOGRAPHY

DeBakey, M. E.: A New Blood Transfusion Needle,
Am. J. Surg., 26:592-593 (December) 1934.

DeBakey, M.: Anticipating Some Difficultie {During
Transfusion of Unmodified Blood, Am. J. Surg.,
27: 85-92 (January) 1935.

DeBakey, M. and Honold, E.: Blood Transfusion,
Internat. M. Digest, 33:301-313 (November),
eoag (December) 1938; 34:49-60 (January)

Kilduffe, R. A. and DeBakey, M The Blood Bank
and the Technique and Therapeutics of Trans-
fusion, St. Louis, C. V. Mosby Co., 1942.

Strumia, M. M. and McGraw, J. J.: Frozen and

Dried Plasma for Civil and Military Use, J. A.
M, A., 116: 2378-2382 (May 24) 1941.

Strumia, M. M. and McGraw, J. J.: The Preparation
and Preservation of Human Plasma, Am. lin,
Path,, 11:175-194 (March), 288-306 (Koh, Cee:
401 (May), 480-496 (June) 1941.

Strumia, M. M. and McGraw, J. J.: The Develop-
ment of Plasma Preparations for Transfusions,
Ann, Int. Med., 18:80-88 (July) 1941.

Strumia, M. M., Newhouser, L. R., Kendrick ”
Jr. and McGraw, J. Su: Development of Equi:
ment for Administration of Dried Plasma in the
re Forces, War Med., 2:102-113 QJanuary)