Vol. 19, No.
2 February 1997
Continuing Education Article
FOCAL POINT
★Many transfusion reactions can
be prevented.
KEY FACTS
■ The most important decision
is whether transfusion is truly
needed.
■ Blood component therapy can
be less risky than transfusion
of whole blood.
■ Unless the blood type of the
recipient is known, universal
blood should always be used.
■ A crossmatch should be
performed for all dogs receiving
red cells, even if universal blood
is used.
■ The severity of most transfusion
reactions is dose dependent, and
early recognition of a reaction
can avert disaster.
Canine Transfusion
Reactions. Part II.
Prevention and
Treatment
North Carolina State University University of Minnesota
Karyn Harrell, DVM Janice Parrow, CVT, LATg
Novo Nordisk
Gentofte, Denmark
Annemarie Kristensen, DVM, PhD
R ecent advances in transfusion medicine and the increased availability of
canine blood components have made transfusion an important part of
veterinary medicine. Transfusion is potentially life-saving, but it carries
some risk. Part I discussed the immunologic and nonimmunologic causes of
transfusion reactions. This part discusses the prevention and treatment of
transfusion reactions.
PLANNING TRANSFUSION THERAPY
The most important decision a clinician must make is whether transfusion
therapy is truly needed. An accurate assessment of the animal’s overall condi-
tion and prior history must be made; the decision to use blood components
should not be based on numbers alone.1–3 As with all forms of medical therapy,
avoiding unnecessary drug administration is the first step in preventing unde-
sirable complications.
After deciding to initiate transfusion therapy, the veterinarian must carefully
choose the component to be given. The use of whole blood has been dramati-
cally reduced recently in human and veterinary medicine.2,4–6 More precise and
efficient replacement for distinct deficiencies can be accomplished through the
use of specific component therapy.
Use of component therapy will also decrease the risk of transfusion
reactions.4–7 If only coagulation factors are needed, plasma or cryoprecipitate is
the most appropriate therapy; hemolytic reactions can thus be avoided. A dog
that is anemic and has significant heart disease will be less likely to develop cir-
culatory overload if packed red cells are given instead of whole blood. Reviews
Small Animal The Compendium February 1997

of the indications for administering specific blood com- curate card test for dog erythrocyte antigen (DEA) 1.1 is
ponents have been published.5,8 now available. This test allows for the immediate identi-
fication of the DEA 1.1 status of donor and recipient.
SELECTING DONORS Donor dogs can then be typed for other important anti-
Blood Type gens by established laboratories. 13,14 Although most
Many transfusion reactions can be prevented simply donors should have the universal blood type, donors of
by following appropriate transfusion medicine guide- other blood types may be used when the recipient’s
lines (see Preventing Transfusion Reactions in Dogs) blood type is known to be compatible (DEA 1.1–posi-
when choosing donors, collecting and preparing blood tive blood may be given to a DEA 1.1–positive patient).
products, and administering these products to patients.
Several of these points warrant further discussion. Crossmatching
Not all DEA groups have been well characterized, so
Nonuniversal Blood a crossmatch should be performed for all dogs receiving
Use of nonuniversal blood increases the risk of acute red blood cells—even when universal blood is used.15 A
hemolytic transfusion reactions in a sensitized patient full crossmatch includes a major part (which tests for
and might induce antibody formation in the recipi- antibodies in the recipient’s blood to the donor’s red
ent.4,5,7,9,10 These antibodies will decrease survival of cells) and a minor part (which detects antibodies in the
donor red cells and sensitize the patient to additional donor’s blood to the recipient’s red blood cells).3,7,15,16
transfusions. Transfusion of nonuniversal blood to a Controls testing reaction of the recipient’s cells with its
bitch might lead to neonatal isoerythrolysis in puppies own serum and the donor’s cells with its own serum are
that are subsequently born.8,11,12 also run. Unless large quantities of plasma are trans-
Unless the blood type of the recipient is known, uni- fused, a minor crossmatch is unnecessary.7,15
5,9,13
versal blood should always be used. A quick and ac- A major crossmatch is a superb screening test for in-
compatibilities that could cause
Preventing Transfusion Reactions in Dogs serious hemolytic transfusion re-
actions.3,7,16 This test is especially
useful for patients that have been
Donor* ■ Administer diphenhydramine previously transfused (antibodies
■ Type all donors—at least for (0.5 mg/kg subcutaneously or can form in as few as 4 days), in
DEA 1.1. intramuscularly). patients with natural antibodies,
■ Screen for metabolic and and in multiparous females.3,15,16
infectious diseases. Administration The major crossmatch (see the
Major Crossmatch protocol) is
■ Use sterile technique when ■ Never use outdated or hemolyzed
simple and can be performed in
collecting blood. products. any clinic with a centrifuge, a
■ Use appropriate separation ■ Use only isotonic saline to dilute heat block, and a microscope.
methods, and store blood packed red cells. Antigen–antibody reactions
products at suggested ■ Warm blood products to can be temperature dependent.
temperatures. appropriate temperatures. Consequently, the crossmatch is
run at 37˚C, 25˚C, and 4˚C. 3
■ Avoid mechanical damage to
Red blood cells that show a reac-
Recipient cellular components by using tion at 37˚C or 25˚C should not
■ Perform a major crossmatch. appropriate pumps, filters, needle be given. It may also be necessary
■ Use universal blood (unless the sizes, and administration rates. to compare the results with the
patient’s blood type is known). ■ Use warmed or open units within self-controls (especially in cases of
■ Consider the patient’s underlying 24 hours. immune-mediated hemolytic
anemia) and determine a “best
diseases when choosing ■ Complete each transfusion within
fit” transfusion.
components and administration 4 hours. The incidence of hemolytic
rate. ■ Monitor transfusions carefully. transfusion reactions will be re-
*Screened and typed canine blood products can also be obtained from an established duced by performing crossmatch-
blood bank. es when red cells are given. Even
when blood showing a compati-

DEA 1.1 ■ NATURAL ANTIBODY ■ MULTIPAROUS FEMALES

The Compendium February 1997 Small Animal

ble crossmatch is given, however, certain reac-

tions may still occur.7,15,16 As a crossmatch tests Major Crossmatch
only for preexisting antibodies, posttransfusion
sensitization may occur—even when appropri- ■ Collect 2 ml of EDTA ■ Place two drops of the
ately matched blood is given (which emphasizes anticoagulated blood recipient’s plasma or
the need to use universal red cells).7,16 A mild from donor and recipient. serum and two drops
hemolytic reaction may also occur when anti-
(Pigtails on stored blood of the donor cell
bodies are present at levels too low for the cross-
match to detect. In addition, a crossmatch does can be used.) suspension in a 3-ml
not test for antibodies to white blood cells or ■ Centrifuge the blood test tube. Mix well and
platelets; these antibodies may be responsible samples for 1 minute incubate tubes for 30
for mild to severe nonhemolytic reactions.17–20 (1000 rpm); remove the minutes at room
plasma to prelabeled temperature. Centrifuge
Prophylactic Treatment
tubes. for 1 minute at 1000 rpm.
The benefit of prophylactic treatment for the
prevention of type I hypersensitivity reactions ■ Wash the donor cells: ■ For controls, follow the
has been debated.5,21 In one experiment, an an- Make a 2% suspension of same procedure as in the
tihistamine given before plasma transfusion pre- red blood cells by taking previous step but place
vented acute hypersensitivity reactions. 21 No 0.1 ml of the red blood the recipient’s cells with
controlled clinical or prospective studies have cells and adding 5 ml of the recipient’s plasma or
been published to date. Although we are cur-
0.9% saline; mix the serum and the donor’s
rently unable to document a definitive decrease
in type I reactions when an antihistamine is giv- suspension. cells with the donor’s
en in clinical cases, diphenhydramine (0.5 ■ Centrifuge the suspension plasma or serum.
mg/kg intramuscularly or subcutaneously) may for 1 minute. Discard the ■ To read the tubes:
reduce the risk of these reactions. Glucocorti- supernatant. Resuspend ■ Check for agglutination.
coids do not acutely suppress the production of the red blood cells in ■ Check for hemolysis.
IgG or IgM antibodies. For this reason, admin- ■ Place a drop from the
another 5 ml of 0.5%
istration of glucocorticoids before red cell tube on a slide and ex-
transfusions will not prevent a hemolytic trans- saline. Repeat this amine under the micro-
fusion reaction from occurring when incompat- procedure twice more. scope for agglutination.
ible blood is given to a sensitized patient.7,22 In
addition, steroids do not prevent the binding of
IgE to mast cells or the subsequent release of vasoac- checked at 15, 30, and 60 minutes into the transfusion
tive cellular products. Thus, there is no reason to ad- and at 1, 12, and 24 hours after transfusion.5 When red
minister steroids in an attempt to prevent a type I hy- cells are given, packed cell volume is recorded and
persensitivity reaction. Steroids should be given only if serum examined for hemolysis at 15 minutes and at 1,
necessary to treat the primary disease or to treat shock 12, and 24 hours after transfusion. More specific infor-
if a severe transfusion reaction does occur. mation (e.g., blood pressure, coagulation testing, renal
function) may be collected as needed.
Monitoring It is also useful to record the primary disease, a sum-
The severity of most transfusion reactions is dose de- mary of prior transfusions or reactions, the component
pendent; early recognition of a problem can avert disas- and specific donor used, crossmatch information, and
ter. Careful patient observation is critical, especially premedications or other therapy. If a reaction does oc-
during the first 30 minutes of the transfusion.5,18,21,23,24 cur, particular details should be summarized. Conscien-
Accurate monitoring is facilitated by the use of a stan- tious monitoring and documentation will enhance ear-
dardized form to record significant data. ly recognition of reactions and aid in the identification
When any blood component is to be given, baseline of the overall incidence of problems in the transfusion
measurements of temperature, pulse, and respiratory practices in your clinic.
rate should be recorded. Mucous membrane color,
packed cell volume, total protein, a coagulation factor TREATMENT
test, and platelet count should also be noted. The tem- If a reaction is suspected, the transfusion must be
perature, pulse, and respiratory rate should also be stopped immediately.2,7,11,16,25,26 While the transfusion is

DIPHENHYDRAMINE ■ FEVER ■ HEMOLYSIS

Small Animal The Compendium February 1997

40
60
Other PRBC
35
WB FFP
50
30

Percent of Transfusions
Whole Blood

25 40

20 30

15
20
10
10
5
0 0
1988 1989 1990 1991 1992 1993 1994 1995 1988 1989 1990 1991 1992 1993 1994 1995

1988
Year
Figure 1A Figure 1B
Figure 1—(A) Whole blood has accounted for a declining percentage of all transfusions at the University of Minnesota Veterinary
Teaching Hospital. (B) Fresh-frozen plasma (FFP) and packed red blood cells (PRBC) are increasingly being used instead of
whole blood (WB).

discontinued (for a minimum of 10 to 15 minutes), the
severity of signs is evaluated (see Treatment of Transfu-
sion Reactions). The veterinarian should verify whether
the appropriate administration rate and technique are
being used. The signs of mild febrile or type I hyper-
sensitivity reactions often dissipate, and the transfusion
may be restarted at a slower rate.7,16 External cooling
and antipyretics may be necessary if the fever is persis-
tent or more severe.16,26 Mild to moderate hypersensitiv-
ity reactions (pruritus, erythema, and urticaria) often
respond well to diphenhydramine (1 to 2 mg/kg intra-
muscularly).3,23,27,28 Some clinicians recommend an anti-
inflammatory dose of a glucocorticoid.7,29,30
Hypocalcemia secondary to citrate toxicity is general-
ly transient and reversible by discontinuing the transfu-
sion until the signs subside.7,23 Often, the transfusion
can be restarted at a slower rate without further prob-
lem.3,23,26 Specific therapy with 10% calcium gluconate

Treatment of Transfusion Reactions

General ■ Administer diphenhydramine and/or glucocorticoids.

■ Stop the transfusion. Hemolysis
■ Evaluate specific signs—if mild, restart transfusion ■ Monitor temperature.
at slower rate and monitor closely. ■ Monitor for shock, disseminated intravascular
Fever coagulation, acute renal failure, and sepsis.
■ Consider external cooling and/or antipyretics. ■ Consider the following:
■ Monitor temperature for 24 to 48 hours. ■ Intravenous fluid diuresis
Vomiting ■ Glucocorticoids
■ If mild, restart transfusion at slower rate and ■ Furosemide
monitor for additional vomiting. ■ Dopamine
■ Withhold food and water for 12 to 24 hours (or as ■ Heparin
necessary). Respiratory distress
■ Consider antiemetics and/or intravenous fluids. ■ Administer furosemide.
Pruritus or urticaria ■ Consider oxygen therapy with or without assisted
■ If mild, restart transfusion at a slower rate and monitor. ventilation.

EXTERNAL COOLING ■ ANTIPYRETICS ■ DIPHENHYDRAMINE ■ GLUCOCORTICOID

The Compendium February 1997 Small Animal

TABLE I
Incidence of Reactions to Transfusion of Blood Components
Packed Red
Reaction/Total Total Blood Cells and
Transfusions Incidence Packed Red Fresh-Frozen Fresh Whole Fresh-Frozen
Year (n/n) (%) Blood Cells Plasma Blood Plasma Other

1988 2/48 4.2 0 1 1 0 0

1989 5/134 3.7 1 1 2 1 0
1990 3/186 1.6 1 0 1 1 0
1991 10/322 3.1 2 3 1 2 2 (platelet-rich plasma)
1992 9/271 3.3 4 1 0 4 0
1993 7/328 2.1 4 1 0 1 1 (autotransfusion)
1994 13/376 3.4 8 3 0 2 0
1995 14/413 3.4 3 9 1 1 0
Total 63/2078 3.0

is seldom necessary; if An earlier study of 131 red

TABLE II
needed, it can be adminis-
tered at 50 to 150 mg/kg Frequency of Clinical Signs of Transfusion Reactions ed acute and delayed reac-
slowly to effect.3,4,7,16,27 As
calcium infusion may pro-
Reaction Mild Signs
duce ventricular arrhyth-
mia, the electrocardiogram Fever
must be monitored.26 Se- Vomiting
vere transfusion reactions Facial edema
resulting in shock, dissem- Hemolysis
inated intravascular coagu- Tachypnea/dyspnea
lation, renal failure, respi- Hemolysis (acute)
ratory distress, and sepsis Tremors
must be treated aggressive- Shock
ly. Further information on
the appropriate treatment
of severe reactions has been published.2,4,16,25,30–33
Most of the delayed transfusion reactions that are
recognized are self-limiting.7,2 If transfusion-related dis-
ease transmission is suspected, specific treatment of that
disease is indicated.
INCIDENCE AND CLINICAL SIGNIFICANCE
The incidence of canine transfusion reactions has only
recently begun to be studied. Documentation of an acute
hemolytic transfusion reaction due to DEA 1.1 incompat-
ibility has recently been published.24 A 1992 study of 307
red blood cell transfusions given over a 1-year period at
the University of Pennsylvania Veterinary School docu-
mented 10 acute reactions (3.3%).34 All were mild and
self-limiting and consisted of pyrexia (4 dogs), vomiting (4
dogs), and facial edema (2 dogs). Most of these dogs had
been crossmatched, and no hemolytic reactions were seen.
blood cell transfusions evaluat-
Frequency tions.35 Seventeen dogs (13%)
exhibited adverse side effects,
Severe Signs
with 10 dogs having an acute
41 — reaction (emesis, hemolysis,
13 — hematuria, or icterus); 7 dogs
6 — exhibited delayed hemolysis.
3 — None of these reactions were
2 1 fatal. A crossmatch was not
1 1 performed on all of these dogs.
1 — We have recently tabulated
— 1 the results from an 8-year ret-
rospective study conducted at
the University of Minnesota
Veterinary Teaching Hospital and documenting the in-
cidence and clinical significance of transfusion reac-
tions. Transfusion request forms were reviewed for pos-
sible adverse reactions from the period of September 1,
1988 through December 31, 1995. The complete clini-
cal record of any dog listed as having a transfusion reac-
tion was reviewed to confirm that a reaction occurred
and to determine the type and outcome of that reac-
tion. Most of the blood products used were from in-
house universal donors. Crossmatches were conducted
for 85% of the dogs receiving red blood cells, and most
of the dogs were pretreated with diphenhydramine.
From 1988 to 1995, the use of whole blood de-
creased dramatically and there was a concurrent rise in
the use of specific components (Figure 1). This trend
agrees with other reports.6,34,35 The specific components
(excluding autotransfusion) used in the last 3 years of

DELAYED REACTIONS ■ FOLLOW-UP ■ DOCUMENTATION

 Small Animal The Compendium February 1997
Atlas of Breed-Related
Canine Ocular Disorders the study included packed red cells (40.8%), plasma
products (56.0%), and whole blood (3.2%).
the ultimate visual diagnostic guide A total of 2078 transfusions were given over the 8-
year period. Sixty-three suspected acute or delayed reac-
tions occurred (3.0%). Table I gives a breakdown of the
Atlas of yearly results. The vast majority of these reactions
Breed-Related (92%) were acute hypersensitivities or febrile reactions.
Canine Ocular Two (3.2%) acute and three (4.8%) delayed hemolytic
Disorders reactions also occurred. Additional delayed reactions
may have been missed because of inadequate follow-up.
No nonimmunologic reactions were documented.
Table II summarizes the variety and incidence of clini-
Kerry L. Ketring
Mary B. Glaze cal signs observed during these transfusion reactions.
Although the use of specific component therapy in-
140 pages, creased dramatically over the 8-year study period, the
incidence of reactions did not decrease significantly,
85
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$95* Kerry L. Ketring • Mary B. Glaze Fever and vomiting were the two most common side
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sponded well to slowing or discontinuing the transfu-

A
unique compilation of exceptional-quality, full- sion, administration of diphenhydramine, and/or mild
color photographs illustrating the full range of cooling techniques. One death was attributed to acute
inherited ocular diseases recognized in the dog. shock. The remaining two dogs with severe reactions
A lifetime resource that will never go out of date by two (consisting of pulmonary edema, pyrexia, and acute
noted experts, one university affiliated, the other in hemolysis) recovered completely with supportive thera-
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private referral practice! Serves as a companion to Ocular
and administration of diphenhydramine, furosemide,
Disorders Presumed to be Inherited in Purebred Dogs, the dexamethasone, aminophylline, and oxygen therapy. As
report of the Genetics Committee of the American previously stated, approximately 15% (140 of 943) of
College of Veterinary Ophthalmology. the red cell products were not crossmatched. One
hemolytic and 10 nonhemolytic reactions occurred af-
FEATURES ter these uncrossmatched transfusions. Eleven percent
of the animals did not receive prophylactic treatment.
■ Concise and well-organized by
Appropriate Only 0.1% (1 of 104) of these animals exhibited a
anatomic feature for general transfusion reaction. A well-controlled prospective
■ Over 350 color images enhanced practitioners, study is needed before conclusions can be drawn about
by arrows students/residents the effect of crossmatching and prophylactic treatment
■ Captions discuss history, signs, in training, and in canine transfusion medicine. Adequate monitoring
evaluation, and case highlights breeders and continued reporting of the significance and inci-
dence of transfusion reactions are also needed in order
■ Separate index of all included
Second in a series to enhance the ability of veterinarians to safely adminis-
breeds by the authors of ter transfusions to dogs.
■ High-gloss finish and spiral bind- Atlas of Feline
ing—ideal for use as a diagnostic Ophthalmology CONCLUSION
guide and client education tool When appropriately prepared and administered, trans-
■ Extensive current bibliography for further information fused blood products can be an extremely useful and
low-risk form of therapy in veterinary medicine. Recent
on treatment
advances in transfusion medicine, along with the in-
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CROSS-MATCHING ■ PROPHYLAXIS
The Compendium February 1997
clude an awareness of possible adverse effects. Veterinari-
ans who understand the underlying mechanism of trans-
fusion reactions can prevent many of these reactions.
About the Authors
Dr. Harrell is affiliated with the Department of Companion
Animals and Special Species Medicine, College of Veteri-
nary Medicine, North Carolina State University, Raleigh,
North Carolina. Dr. Kristensen is affiliated with Novo
Nordisk in Gentofte, Denmark, and is a Diplomate of the
American College of Veterinary Internal Medicine. Ms.
Parrow is affiliated with the Department of Small Animal
Medicine and Surgery, College of Veterinary Medicine,
University of Minnesota, St. Paul, Minnesota.
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???? ■ ???? ■ ???? ■ ????
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