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SCIENTIFIC SECTION

REVIEW ARTICLE

Clinical use of blood, blood components and blood products


MORRIS A. BLAJCHMAN,* MD, FRCP[C]; FRANCES A. SHEPHERD,t MD, FRCP[C];
ROGER A. PERRAULT,. MD, PH D

The goal of modern transfusion therapy is to provide appropriate replacement During the past 10 years significant
therapy with blood components as opposed to whole blood for patients progress has been made in the tech-
with specific hematologic deficiencies. A prerequisite of component therapy is, nology of blood component prep-
therefore, correct identification of the deficiency. Appropriate use of components
avoids many of the hazards associated with the use of whole blood, and at aration and storage. Each unit of
the same time makes maximal use of this valuable resource. Blood components whole blood appropriately separ-
separated from whole blood soon after collection and appropriately stored ated and fractionated can now pro-
can, in combination, provide all the factors present in fresh whole blood. vide red blood cells, platelets, fresh
Red cell concentrates prepared from multiple packs have a hematocrit of frozen plasma, stored plasma (plas-
approximately 70Gb. They may be stored for up to 3 weeks at 40G and ma depleted of some of the labile
are recommended for most situations requiring red cell transfusions. Platelet clotting factors), cryoprecipitated
concentrates, which can be stored for up to 72 hours at 22C, may be used for factor VIII, albumin, gamma glo-
thrombocytopenic patients. Fresh frozen plasma, stored plasma, cryoprecipitated bulin and factor IX concentrate
factor VIII, factor VIII concentrate and factor IX complex concentrate are
available for the proper treatment of patients with hemorrhagic disorders (containing factors II, VII, IX and
due to coagulation factor deficiencies. Similarly, albumin and immune serum X). Additionally, other products,
globulin are available for their oncotic and antibody properties respectively. such as specific hyperimmune gam-
Thus, the availability and appropriate use of the various blood products allows ma globulin preparations, are avail-
not only optimal transfusion therapy for each patient, but also fuller utilization able to prevent certain infections
of national blood resources. and specific sensitization (e.g., he-
molytic disease of the newborn).
L'objectif de Ia th6rapeutique transfusionnelle moderne est de satisfaire Because these blood products are
aux besoins des patients souffrant d'une affection hematologique specifique readily available for patient care,
au moyen de fractions du sang plut6t qu'au moyen du sang total. L'essence the physician can select a blood
de Ia therapeutique des fractions consiste donc a identifier d'une fa9on component appropriate to a pa-
pr6cise Ia deficience dont souffre le patient. L'utilisation judiciouse des
fractions permet d'eviter un grand nombre des dangers associes a Ia transfusion tient's specific needs, thereby avoid-
du sang total tout en favorisant l'utilisation maximale et rationnelle de cette ing many of the hazards associated
source de vie. Lorsque le fractionnement a lieu peu apres le prelevement with the use of whole blood.
et que les fractions sont entreposees de fa.on adequate, elles conservent Despite this ready availability of
toutes les propri6tes du sang total. L'on obtient ainsi des suspensions all blood components and fractions
d'h6maties d'une concentration d'environ 700/0 dont Ia periode maximale
de conservation est de 3 semaines a 40C; on recommande le recours a ce
type de concentre pour Ia plupart des situations exigeant Ia transfusion * Medical director, Hamilton centre,
d'hematies. Ouant aux concentres de plaquettes, ils peuvent .tre conserves and chairman, blood components
pendant 72 heures a 22C et servent au traitement des thrombocytopenies. Pour committee, Canadian Red Cross Blood
ce qui est du plasma frais congele, du plasma conserve, du cryoprecipite de Transfusion Service
IMedical services director, Canadian
facteur VIII, du concentre de facteur VIII et du concentre du complexe de Red Cross Blood Transfusion Service
facteur IX, ils constituent le traitement le mieux adapte des affections .National director, Canadian Red Cross
h6morragiques engendrees par une carence en facteurs de Ia coagulation. Blood Transfusion Service
L'albumine est utilis6e pour ses proprietes oncotiques et l'immunoglobuline Reprint requests to: Dr. Morris A.
s6rique pour son activite anticorps. Ainsi, Ia disponibilite et l'utilisation judicieuse Blajchman, Hamilton Centre of the
de ces differentes fractions sanguines permet Ia traitement optimal et Canadian Red Cross Blood Transfusion
personnalise de chaque affection sanguine tout en favorisant une meilleur Service, 299 Main St. E, Hamilton,
utilisation des ressources nationales de sang. Ont. L8N 1H8
OMA JOURNAL/JULY 7, 1979/VOL. 121 33
Table I-Characteristics of whole blood and red cell concentrates
Characteristic Whole blood Red cell concentrate
Volume, ml 500 25 300 25
Hematocrit, % 40 ± 5 70 5
Red cell volume, ml 200 :1: 25 200 :1 25
Plasma volume, ml 300 25 100 25
Albumin content, g 10 - 12 4 - 5
Fresh whole blood Platelet concentrates may be stored is less than expected may be due
in this volume for up to 72 hours to infection, platelet antibodies,
A request for fresh whole blood without a reduction in pH to less splenomegaly or fever. The pres-
should indicate an unusual clinical than 6.0, a level below which plate- ence of antibodies against histo-
situation that the attending physi- lets do not appear to be hemo- compatibility (HLA) antigens on
cian believes cannot be met by the statically functional."'4 Platelet platelets should be considered in
use of stored components. In most concentrates are stored at the re- patients who initially respond well
instances the term fresh blood gional Blood Transfusion Service to infused platelets but then be-
means blood that has been stored centre at 220C with continuous come refractory. In such instances
for less than 24 hours. Thus, the gentle agitation. This temperature the use of histocompatible platelets
use of fresh blood may require ensures optimal survival and hemo- has been effective.'7
that all of the appropriate tests static function, and the agitation It is preferable to give platelets
usually performed cannot be done, prevents the formation of platelet from ABO-compatible donors.
so that the recipient is subject to aggregates. Platelets thus prepared However, satisfactory clinical re-
unnecessary risk. In very few clin- and stored are acceptable for clin- sults may be obtained with ABO-
ical situations is there a need for ical use for up to 72 hours after incompatible platelets, and one
fresh blood that could not be met collection of the unit of blood from should not hesitate to use them if
equally well with the informed use which the platelets were ex- ABO-compatible platelet concen-
of appropriate components.8 tracted.'1'12 Bacterial contamination trates are not available.18
If the perceived clinical need for and proliferation in a very low fre- Platelets do not contain the
fresh whole blood is maximal surv- quency occur with storage at 220C, Rhesus (D) antigen, but all platelet
ival of red cells and optimal oxy- but the risk is minimal if the blood preparations contain a small quan-
gen carriage, red cell concen- is collected with strict precautions. tity of red cells (approximately 0.4
trates less than 7 days old are Nevertheless, the possibility of bac- ml per unit of platelet concentrate).
indicated. If the clinical need is terial contamination must be con- The Rh immunization of an Rh-
for blood with minimal plasma sidered if chills and fever occur negative woman could occur fol-
electrolyte concentrations, red cell during or shortly after the platelet lowing the infusion of platelet con-
concentrates less than 7 days old infusion.15"0 There appears to be a centrates from an Rh-positive
from which the supernatant plasma progressive decrease in the hemo- donor.'9 If platelets from an Rh-
has been removed are indicated. static effectiveness of platelets with positive donor must be given to an
If the clinical need is for labile storage; thus, platelets should be Rh-negative woman of childbear-
coagulation factors, red cell con- administered promptly after they ing age or a girl who has not
centrates plus fresh frozen plasma are received from the transfusion reached the childbearing age, it is
or cryoprecipitate should be rec- centre. Each unit of platelet con- recommended that Rh immunoglo-
ommended. If the clinical need is centrate contains, on the average, bulin be administered with or im-
for platelets, red cell concentrates 6 x 1010 viable platelets. mediately after the platelets, while
plus platelet concentrates may be From clinical experience we the hemostatic effect of the plate-
indicated. Blood less than 1 week know that few patients bleed spon- lets is still present. Preparations of
old stored in citrate-phosphate- taneously with platelet counts great- Rh immunoglobulin designed for
dextrose has nearly normal 2,3- er than 40 x 10./l unless they intravenous use are available in
diphosphoglycerate (2,3-DPG) con- have a concomitant defect in plate- some countries. In Canada such a
centrations and a nearly normal let function. If platelet transfusions preparation is undergoing clinical
pH. Therefore, red cell concen- are required by a patient, the ap- trial. When available, such a
trates less than 1 week old are propriate number of units of plate- product should be given to throm-
probably preferable to whole blood let concentrate are pooled prior to bocytopenic individuals in whom
to prevent volume overload in neo- administration. This should be intramuscular injections are contra-
nates who are very ill. done with sterile transfer tubing or indicated.
specific packs. An adult weighing Significant progress has been
Platelet transfusions 60 kg who requires a platelet trans- made in the preparation, storage
fusion needs approximately eight and use of platelet transfusions.
Platelets may be provided to in- units of platelet concentrate. The However, present knowledge allows
dividuals who are deficient in this platelets should be administered storage for only up to 72 hours,
blood component through the use rapidly through an administration and this short shelf-life results in
of platelet concentrates.9" The use set with a filter. As a general rule, a large amount of wastage. The fu-
of fresh whole blood is generally one unit of platelet concentrate will ture of platelet technology will be
contraindicated because of the raise the platelet count in the aver- enhanced by the development of
large volume that would be re- age-sized adult by approximately methods that allow for long-term
quired to correct the platelet defi- 5 x 10./l, measured 1 hour after storage by freezing,20'2' but current
ciency. Each unit of platelet con- infusion. freezing techniques result in poor
centrate is obtained from an in-. A variety of factors may influ- recovery (25% to 50%) after
dividual unit of fresh whole blood ence the recovery of infused plate- transfusion. The use of autologous
and is usually prepared in a volume lets. An increment in platelet count frozen preserved platelets in leuke-
of approximately 50 ml of plasma.1' following platelet transfusion that mic patients has recently been re-
CMA JOURNAL/JULY 7, 1979/VOL. 121 35
Table li-Blood groups of plasma that may
be infused into recipients

Recipient's Donor's
blood group blood group
0 0,A,B,AB
A A,AB
B B,AB
AB AB
istered as individual units or a pool with factor VIII. However, the is a fractionated blood product ob-
of several units. most satisfactory and safest way totained from pooled plasma. Despite
If a diluent is required, small judge the dosage is to measure the its name this preparation contains,
quantities of normal saline may be patient's circulating factor VIII in addition to factor IX, factors II,
introduced through an outlet site concentrations during treatment. VII and X, also in concentrated
in the cryoprecipitate bag after Cryoprecipitated factor VIII is form. This product is distributed in
thawing. Each bag should be gently a freeze-dried form in vials con-
to be used primarily for factor VIII
agitated to ensure complete disso- replacement in classic hemophilia. taining 500 units of factor IX and
lution of the cryoprecipitate. The requires reconstitution prior to in-
It may also be used in patients with
dissolved cryoprecipitate should be von Willebrand's disease as a travenous use. The quantity of the
administered through a filter; a source of both factor VIII and von other coagulation factors in each
convenient method is to use a spe- Willebrand's factor. In patients vial varies but is approximately
cial infusion set that is available with disseminated intravascular co-50% of that of factor IX.
for the infusion of small volumes agulation, in whom both factor VIII This preparation is indicated
of blood components. and fibrinogen may be required, primarily for use in patients with
Cryoprecipitate units are usually congenital factor IX deficiency
cryoprecipitate is probably the pre-
labelled with the ABO group of the ferred therapeutic agent. Occasion-(Christmas disease). To arrest
donor, and it is preferable, but not ally following the massive replace-bleeding in such circumstances re-
essential, to give units that are ment with stored blood there is a quires increments similar to those
blood group compatible. Hemolytic reduction in the concentration of recommended for patients with fac-
episodes have occasionally been re- tor VIII deficiency. The average
circulating factor VIII. In such in-
ported when incompatible units half-life of factor IX in vivo has
stances fresh frozen plasma or cryo-
have been given; for example, if precipitate may be administered. been found to be between 15 and
cryoprecipitate from a group 0 Because of the risk of hepatitis20 hours; adequate levels may
donor is given to a group A individ- therefore be achieved with daily in-
following their use, fibrinogen prep-
ual with hemophilia the anti-A, if arations are no longer made avail- fusions.
present in a high titre, may sensitize able by the Canadian Red Cross Factor IX complex concentrate
the recipient's red cells, causing is contraindicated in patients with
Blood Tranfusion Service.27 Instead,
hemolysis.TM cryoprecipitate is recommended in liver disease and in neonates be-
The concentration of circulating the rare clinical circumstances in cause thrombosis or disseminated
factor VIII required in persons with which fibrinogen is indicated. Eachintravascular coagulation may oc-
hemophilia depends on the clinical cur following infusion. This has
unit of cryoprecipitate contains ap-
situation; the following concentra- proximately 200 mg of fibrinogen. been attributed to the presence of
tions have been suggested:. activated clotting factors in some
* For minor hemorrhage and Factor VIII concentrate preparations of factor IX complex
Prophylaxis approximately 15% of Since 1968, methods have been concentrate that are not removed
normal. efficiently in patients with liver dis-
available to fractionate factor VIII
* For minor surgical proce- from fresh frozen plasma..'29 This ease and in neonates, all of whom
dures approximately 30% of nor- have low circulating concentrations
results in a freeze-dried preparation
mal. of antithrombin III...
that does not require special storage
* For major surgical proce- conditions and is more convenient The use of factor IX complex
dures approximately 40% to 50% to use than cryoprecipitated factorconcentrate has been reported to
of normaL VIlI or plasma. It is easily recon-be effective in persons with hemo-
The half-life of transfused factor philia who have acquired inhibitors
stituted just prior to use, and since
VIII in vivo is approximately 12 it can be stored at room tempera- (antibodies) to factor VIII.. Cer-
hours, and this should be remem- ture it has offered the person withtain factor IX complex preparations
bered in planning replacement ther- hemophilia a previously unknown have been shown to have factor
apy. freedom to travel. Such prepara- VIII bypassing activity. The mech-
The increment in the factor VIII anism of this activity is uncertain
tions allow effective doses of factor
concentration obtained with each VIII to be infused in small volumesand may be similar to the mech-
bag of cryoprecipitate is variable and are of particular value in the anism causing disseminated intra-
and depends on the blood volume vascular coagulation in patients
treatment of patients with inhibitors
of the recipient. The presence of to factor VIII.30 Factor VIII con- with liver disease and in neonates.
inhibitors, the specific activity of A trial of therapy with factor IX
centrates may not be as effective as
the preparation and other factors cryoprecipitated factor VIII in thecomplex concentrate is therefore
may also influence the in vivo re- treatment of bleeding episodes in indicated in bleeding persons with
covery of factor VIII. The average patients with severe von Wille- hemophilia if antibodies are present
response is an increase of approxi- brand's and other measures to achieve he-
disease; therefore, in such
instances, cryoprecipitate may be mostasis have failed.
mately 2% in the factor VIII
concentration with each bag of the preferred therapeutic agent.31 Although the plasma used to
cryoprecipitate infused into an prepare factor IX complex con-
adult. Dosage formulas are avail- Factor IX complex concentrate centrate has been tested by radio-
able as rough guides for therapy Factor IX complex concentrate immunoassay and found to be neg-
CMA JOURNAL/JULY 7, 19791 VOL 121 39
ative for hepatitis B surface an- less the pathologic condition re- complement system activation may
tigen (HB5Ag) the possible trans- sponsible for the hypoproteinemia result if it is infused intravenously.39
mission of the hepatitis B virus with can be corrected, albumin can af- The following specific immuno-
the use of factor IX complex con- ford only transient symptomatic or globulins are also available for use
centrate cannot be excluded.36 supportive relief. in the appropriate clinical circum-
A 5% albumin solution may be stances.
Albumin used in the treatment of shock due Rh4D) immune globulin
to hemorrhage or surgery, to re-
Albumin is a serum protein with place protein and fluid lost after This preparation is IgG anti-D
a molecular weight of approximate- extensive burns or to replace plas- derived from the plasma of Rh-
ly 65 000 daltons. It serves pri- ma during manual or automated negative volunteers who have pro-
marily to maintain the capillary os- plasmapheresis. duced anti-D following immuniza-
motic pressure and to act as a Because the 25% albumin solu- tion. In Canada each vial of Rh
carrier protein for various drugs, tion will increase the osmotic pres- immune globulin contains 300 .g
hormones, enzymes and metabolites sure in the circulation without sig- of IgG anti-D. Rh.(D) immune glo-
(e.g., bilirubin). The concentration nificantly increasing the circulating bulin is used for the prevention
of albumin in the plasma is deter- plasma volume, it may be used with of sensitization (alloimmunization)
mined by its synthesis and destruc- or without diuretics to promote of Rh-negative women by their
tion; hypoalbuminemia may be the transient diuresis in the patient with Rh0(D)-positive fetuses.40'41 It re-
result of pathophysiologic processes hypoproteinemia and edema, or to duces substantially the frequency of
affecting either of these processes.37 maintain the blood pressure during Rh alloimmunization when admin-
Preparations of albumin are renal dialysis. If diluted with either istered within 72 hours of the birth
available for the treatment of burns normal saline or 5% glucose in of an Rh-positive infant.
and shock. This fractionated blood water, 25% albumin may also be The frequency of Rh0(D) alloim-
product is prepared from pooled used for volume replacement. munization in Rh-negative women
plasma and is supplied in concen- can thus be reduced by the admin-
trations of 5 and 25 g/dl. The 5% Immune serum globulin istration of appropriate quantities
solution is distributed in 500-ml of Rh immune globulin in a num-
volumes and is osmotically equiva- Preparations of immune serum ber of instances:
lent to an approximately equal vol- globulin containing primarily IgG * After the birth of an Rh-
ume of citrated plasma. The 25% are available for use in the preven- positive child.
solution, which is available in vol- tion or amelioration of some viral * After abortion.
umes of 50 and 100 ml, is osmo- diseases (e.g., infectious hepatitis) * After amniocentesis or ab-
tically equivalent to five times the and may be useful for replacement dominal trauma, or when serious
volume of normal plasma. Both therapy in patients with hypogam- antepartum hemorrhage occurs.
preparations have a physiologic pH maglobulinemia. Immune serum * Antenatally to prevent the
and a sodium content of approxi- globulin has proven useful in the Rh immunization that occurs dur-
mately 145 ± 15 mmol/l. This treatment of congenital immuno- ing pregnancy in approximately
product contains neither coagula- deficiency disorders characterized 2% of Rh-negative women. Such
tion factors nor blood group anti- by an inability to form circulating alloimmunization during pregnancy
bodies. antibodies. Monthly injections of can be greatly reduced by the ad-
There are few complications fol- 0.66 ml/kg of body weight should ministration of Rh immune globu-
lowing albumin infusion. The main be administered. Although its value lin at 28 weeks' gestation.42
complication is excessive volume in the treatment of acquired hypo- * When screening tests for
expansion, which may follow the gammaglobulinemia has been less transplacental hemorrhage indicate
use of the 25% solution, which is well documented, immune serum a large fetal-maternal hemorrhage
hypertonic and therefore capable globulin has been used in similar 20 .g of anti-D should be given
of rapidly expanding the blood doses in the prevention of recur- for every millilitre of Rh-positive
volume. There is minimal risk of rent infections in patients with fetal red cells detected in the ma-
hepatitis following the infusion of chronic lymphocytic leukemia and ternal circulation.
albumin because the method of plasma cell myeloma. * When blood products con-
preparation includes treatment at This fractionated blood product taining Rh-positive red cells are
600C for 10 hours, which macti- is the gamma globulin derived from given to an Rh-negative girl or
yates the hepatitis B virus. large batches of pooled plasma; woman of childbearing age, an ap-
The main clinical uses of albu- therefore, it may contain the IgG propriate quantity of Rh immune
min are the expansion of the blood blood group isohemagglutinins anti- globulin should be given within 48
volume in patients with shock, the A and anti-B. Immune serum glo- hours.
treatment of the protein loss in bulin is supplied as a 16% solution
patients with extensive burns, as an in vials of 2, 5 and 10 ml. It should Hepatitis B immune globulin
adjunct to exchange transfusion in only be given intramuscularly be- This is a fractionated prepara-
neonates with hyperbilirubinemia cause aggregation of IgG molecules tion of immune serum globulin
and as replacement therapy in pa- occurs during preparation and stor- from selected donors whose plasma
tients with hypoalbuminemia.38 Un- age, and adverse effects due to has a high titre of antibody to
40 CMA JOURNAL/JULY 7, 1979/VOL. 121
Table Ill-Coagulant factor content and approximate volume of blood products issued by the Canadian Red Cross Blood Transfusion Service

Coagulation factor*
IX Approximate
II (Christmas volume
Blood product (fibrinogen) (prothrombin) V VII VIII factor) X Xl XIII (ml)
Storedwholeblood + + - + - + + + + 500
Freshfrozenplasma + + + + + + + + + 200
Storedplasma + + - + - + + + + 200
Cryoprecipitated factor VIII + - - - + - - - + 10
Factor VIII concentrate - - - - + - - - - Lyophilized
Factor IX complex concentrate - + - + - + + + - Lyophilized
= present in therapeutic quantities; - = absent in therapeutic quantities.

Table IV-Summary of characteristics and therapeutic use of the products


Blood product Description (per unit) Therapeutic use
Stored whole blood 450 ml of blood taken in 63 ml of citrate-phosphate-dextrose To increase oxygen transport and blood volume.
and stored at 40C for a maximum of 21 days. Labile coagula-
tion factors (V and VIII)absent.
Red cell concentrate Whole blood less 200 . 25 ml of plasma. Hematocrit 70 :i 5%. To increase oxygen transport by increasing the
Stored at 40C for up to 21 days. red cell mass.
Frozen red cells Freeze-preserved for up to 10 years. Negligible amounts of To increase oxygen transport by increasing the
plasma, leukocytes and platelets. red cell mass.
Platelet concentrate Contains approximately 6 x 1010 platelets in 50 ml of plasma. Thrombocytopenia due to decreased platelet
Shelf-life 72 hours. Stored at 220C. production.
Fresh frozen plasma 200 ml of plasma from whole blood removed and frozen within 6 Replacement of coagulation factors not available
hours of collection. Shelf-life 12 months at -300C. Con- as specific concentrates.
tains all coagulation factors.
Stored plasma 200 ml of plasma removed from whole blood within 72 hours of For blood volume expansion and replacement of
collection. Contains all coagulation factors except V and all coagulation factors except V and VIII.
VIII.
Cryoprecipitated factor VIII 80 units of factor VIII in 5 to 10 ml of plasma. Shelf-life 12 Factor VIII replacement in hemophilia and von
months at -300C. Contains approximately 200 mg of fibri- Willebrand's disease. Fibrinogen replacement.
nogen.
Factor VIII concentrate Lyophilized fractionated preparation containing approxi- Factor VIII replacement in hemophilia.
mately 500 units of factor VIII per vial.
Factor IX complex Lyophilized fractionated plasma product containing factors Factor IX replacement. Contraindicated in
II, VII, IX and X. Must be reconstituted prior to intravenous patients with liver disease and in neonates.
use._Factor IX content 500 units per vial.
Albumin Concentration 25 g/dl in vials of 50 or 100 ml, or 5 g/dl in vials For blood volume expansion, hypealbuminemia
of 250 or 500 ml. Low sodium content. and neonatal exchange transfusion.
Immune serum globulin 16% aqueous gamma globulin in vials of 2, 5 and 10 ml for in- Prevention of infections and in patients with
tramuscular injection. hypegammaglobulinemia.

CMA JOURNAL/JULY 7, 1979/VOL 121 41


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42 OMA JOURNAL/JULY 7, 1979/VOL 121