Beruflich Dokumente
Kultur Dokumente
2 February 1997
Canine Transfusion
FOCAL POINT
Reactions. Part I.
★Many transfusion reactions can
be prevented by careful donor
Causes and
selection and proper collection,
storage, and administration of
blood products.
Consequences
KEY FACTS North Carolina State University University of Minnesota
Karyn Harrell, DVM Janice Parrow, CVT, LATg
■ Donors can now be quickly
screened for the highly antigenic Novo Nordisk
blood type DEA 1.1. Gentofte, Denmark
Annemarie Kristensen, DVM, PhD
■ A universal canine blood donor
is negative for all DEA groups
except DEA 4.
also discusses the results of an 8-year retrospective study therefore do not exist in the same animal; they are also
on the incidence and significance of transfusion reac- the most highly antigenic of all the blood types.3,6,8,13,14
tions in dogs. Approximately 60% of dogs carry one of these anti-
gens. At present, no naturally occurring antibodies to
TRANSFUSION REACTIONS these groups have been identified.3 DEA 7 incompati-
A transfusion reaction is any undesirable side effect bility generally results in delayed (3 to 5 days) destruc-
resulting from infusion of blood products. These reac- tion of the transfused red cells.3,14 Although the pres-
tions are generally classified ence of natural antibodies to DEA 7 is somewhat
according to whether they controversial,16 certain reports suggest that these anti-
Classification of are immune-mediated (see bodies do occur in 20% to 50% of DEA 7–negative
5–9
Transfusion Reactions the box). They can be fur- dogs.3,14,17 Because of these problems, it is recommend-
ther categorized by their tim- ed that all donor dogs should be negative for DEA 1.1,
Immunologic ing. An acute reaction occurs 1.2, and 7.3,7,14,18
Acute within minutes of the start DEA groups 3 and 5 are uncommon in the general
■ Hemolysis of a transfusion and up to 48 canine population. A study of greyhounds, however,
hours after the transfusion found that 23% were DEA 3 positive and 30% were
■ Acute hypersensitivity
ends. Later reactions are clas- DEA 5 positive.3 Natural antibodies have also been
■ Platelet sensitivity sified as delayed.10 Under- found in dogs lacking these antigens.3 As with DEA 7,
■ Leukocyte sensitivity standing of the underlying incompatible transfusions result in the delayed destruc-
mechanism helps the veteri- tion of the trans-
Delayed
narian prevent and treat fused red cells. Ca- GLOSSARY
■ Hemolysis transfusion reactions. nine blood donors
■ Posttransfusion should therefore be Allele—a variant of the same gene
purpura CANINE BLOOD TYPES negative for DEA 3
A basic knowledge of ca- and 5. Alloantibody—an antibody directed
■ Neonatal
nine blood groups helps the More than 98% of against an antigen from a member of
isoerythrolysis the same species
veterinarian understand the the canine popula-
■ Immunosuppression
basis for an immune-mediat- tion is positive for Anaphylaxis—a severe, systemic
Nonimmunologic ed hemolytic transfusion re- DEA 4. 3,16 There is hypersensitivity reaction that may re-
action. Canine blood types no evidence for the sult in vomiting, dyspnea, hypoten-
Acute
are named according to the existence of natural sion, seizures, collapse, and shock
■ Pretransfusion surface antigens on the red antibodies to this
hemolysis of donor blood cells (DEA).3,11 An im- antigen, and ac- Natural antibodies—antibodies
cells mune-mediated hemolytic quired DEA 4 anti- found in the serum in the absence of
transfusion reaction occurs bodies are generally any previous, known antigenic stim-
■ Circulatory overload
when a patient has acquired considered to be be- ulation
■ Bacterial 3
antibodies (or, less common- nign. Urticaria—erythematous and ede-
contamination
ly, natural antibodies) to the A universal donor matous pruritic skin lesions; hives
■ Citrate toxicity donor erythrocyte anti- is a dog that is nega-
■ Coagulopathy gens.3,5,11,12 tive for all of the
■ Hyperammonemia Although over 13 different DEA groups except DEA 4.3 Because the purpose of an
■ Hypothermia erythrocyte antigens have erythrocyte transfusion is to maximize the number of
■ Air embolism been defined, only 8 of these viable erythrocytes available to a patient while minimiz-
are accepted as standards. 3 ing the risk of unwanted side effects, all attempts to de-
■ Pulmonary
Table I summarizes canine crease the unnecessary destruction of the donor’s trans-
microembolism blood groups and their fused red cells should be made. Thus, universal red cells
■ Acidosis prevalence in the general ca- should be given whenever possible.
nine population. Laboratory
Delayed
blood typing is currently IMMUNE-MEDIATED REACTIONS
■ Transmission of available for six of these anti- Hemolytic Transfusion Reactions
infectious disease gens.3,8,13–15 Pathophysiology
■ Hemosiderosis DEA 1.1 and 1.2 are al- Antigen-antibody–mediated hemolytic transfusion
lelic (see the glossary) and reactions are classified as type II hypersensitivities and
reactions are allergic or anaphylactic and are classified plement system by leukocyte antigen–antibody interac-
as type I hypersensitivities.9,25,27 These reactions are tions.22,25,31,33 The combination of these mediators may
mediated by IgE antibodies, which can stimulate mast also lead to the accumulation of neutrophils in the
cells to produce or release potent vasoactive sub- lungs, thus possibly resulting in severe respiratory signs
stances. 9,25,27,28 Leukotrienes, prostaglandins, and and shock.25
platelet activating factor are formed from the phospho- A mild fever that begins during the first 30 minutes
lipid membrane of these mast cells.7,25,28 Release of pre- of the transfusion is the most commonly observed
formed compounds (including proteases, serotonin, side effect of leukocyte or platelet sensitivity reac-
histamine, and kallikrein) results in activation of the tions.12,19,22,31,33,34 The fever may increase for up to 8
complement system and formation of the anaphylatox- hours and persist for a total of 20 hours.31 Tremors and
ins C3a and C5a.27–29 The interaction of these media- emesis have also been documented.33 Pulmonary in-
tors can cause not only urticaria and pruritus but also flammatory reactions are infrequent but can be severe
more severe problems (e.g., increased vascular perme- enough to result in adult respiratory distress syn-
ability, bronchoconstriction, and hypotension). drome.25
Administration of plasma products is often consid-
ered risk free and overlooked as a cause of transfusion Delayed Reactions
reactions.29 Plasma products contain alloantigens (albu- Neonatal Isoerythrolysis
min and other proteins), possible allergens (antibiotics Transfusion of DEA 1.1–positive red blood cells to a
or component preparation chemicals), and donor IgE DEA 1.1–negative breeding bitch will result in the for-
antibodies. As a result, transfusion of plasma products mation of potent antibodies against DEA 1.1.35 If this
has been associated with acute hypersensitivity reac- female is bred to a DEA 1.1–positive male, it is likely
tions; these plasma reactions appear to be more com- that some of the pups in the litter will also have DEA
mon than previously recognized.6,12,27,29 1.1–positive blood.9,35 DEA 1.1 antibodies are trans-
Transfusion of plasma containing IgA antibodies to ferred to these puppies via colostrum. As a result,
patients who are IgA deficient and have anti-IgA anti- hemolytic anemia occurs in these neonates after ap-
bodies has resulted in acute hypersensitivity reactions in proximately 3 to 10 days of nursing.35 Clinical signs ob-
humans.25,27 Although these reactions have not been servable by the owner include weakness, failure to
documented to occur in dogs, it is reasonable to con- thrive, and hemoglobinuria.
sider the possibility of their occurrence in breeds that
are predisposed to IgA deficiency. Patients that are Posttransfusion Purpura
atopic or have received multiple transfusions are also at Thrombocytopenia is an infrequent delayed transfu-
a higher risk of an acute hypersensitivity reaction.29,30 sion reaction that has been documented to occur in
Signs of a reaction generally occur within seconds to humans.36 This complication occurs approximately 1
45 minutes from the start of the transfusion.25,27,29 The week after the transfusion and is attributed to platelet
severity of these signs depends on the extent of mast destruction by platelet-specific antibodies. 36 The
cell degranulation and subsequent release of vasoactive thrombocytopenia may persist for 2 months. This dis-
mediators.19,25,26,29 Pruritus, erythema, and urticaria are order is typically self-limiting, and clinical signs are
common allergic reactions in dogs.12,19,22,26 Anaphylactic generally not noted. In rare cases, severe thrombocy-
shock with vomiting, dyspnea, pulmonary edema, topenia has resulted in evidence of bleeding (such as
seizures, and cardiopulmonary arrest may also occur.5,30 petechiae, hematuria, and scleral hemorrhage). The in-
cidence of posttransfusion purpura in dogs is un-
Leukocyte and Platelet Sensitivity Reactions known.
Binding of recipient antibodies to leukocyte and
platelet antigens in donor blood components has been Immunosuppression
documented to cause febrile nonhemolytic transfusion Several published studies have documented post-
reactions in humans.9,22,25,31,32 A febrile nonhemolytic transfusion immunosuppression. For example, transfu-
transfusion reaction is defined clinically as an increase in sion therapy increases renal allograft survival in dogs
body temperature of at least 1°C when no other cause and humans.19,22 Postoperative infections have been
for the fever is found.31,33 These are the most common more frequent in some cancer patients after transfusion;
transfusion reactions seen in humans and may be the the infections were attributed to immunosuppression
source of many febrile reactions in dogs.22,34 Pyrexia is and did not correlate to the severity of the primary dis-
attributed to the release of endogenous pyrogens (e.g., ease.22 The immunosuppression might result from im-
interleukin-1) in addition to the activation of the com- munoregulatory substances in plasma.19
stored, or washed blood products for patients with he- Thus, blood transfusion could transmit Borrelia, result-
patic disease.9 ing in Lyme disease.47 The actual incidence of such
Dilutional coagulopathy may be seen when large transmission is unknown.
amounts of stored blood products that are deficient in Heartworm microfilariae may also be transmitted by
coagulation factors and platelets are rapidly infused.24 transfusion. These microfilariae may confound heart-
Coagulation of the transfused red cells may occur sec- worm testing in the recipient dog but will not cause
ondary to recalcification of the anticoagulant if red clinical disease. Although the prevalence of some dis-
blood cell products are diluted with calcium-containing eases varies geographically, it is generally recommended
solutions (e.g., lactated Ringer’s solution).9 Packed red to screen canine blood donors for heartworm disease,
blood cells should be diluted only with isotonic saline.9 Rocky Mountain spotted fever, ehrlichiosis, brucellosis,
Transfusion of cold blood products may result in hy- babesiosis, and possibly Lyme disease.19,21,22,48
pothermia in young or small animals.24 Significant hy-
pothermia in compromised animals can cause arrhyth- Hemosiderosis
mia and sudden death.33 Mild warming of the infused Hemosiderosis is a form of iron overload that may
product is suggested to avoid this complication.33 occur when multiple red blood cell transfusions are giv-
Pulmonary microembolism may occur because plate- en to a patient that is not bleeding. Hepatic damage
lets, fibrin, and white blood cells form microaggregates may occur because as transferrin becomes saturated, the
in blood that has been stored longer than 7 days.19,24,33 excess iron is stored in the liver.19 Hemosiderosis is un-
These particles are too small to be removed with stan- common and can be prevented by appropriate use of
dard transfusion filters.33 There is much debate about component therapy and by avoiding unnecessary iron
whether these microaggregates could lead to pulmonary supplementation.19
microembolism.19,33 Although it is worthwhile to be
aware of the possibility of this complication, the actual CONCLUSION
occurrence is believed to be low and the routine use of Transfusion reactions can result from immunologic
special filters is unwarranted.19,33 and nonimmunologic mechanisms and can range from
Air embolism can occur when a large amount of air mild and self-limiting to life-threatening. Some of these
(not a few bubbles) is infused. Because closed systems reactions can result from transfusion of incompatible
are now frequently used, this problem is rare; but it blood. Others can result from use of outdated or con-
may occur when glass bottles are vented.9 The clinical taminated blood products or inappropriate administra-
signs are acute cough and dyspnea. tion techniques. Part II will discuss how to prevent
Glucose metabolism in stored blood leads to an in- transfusion reactions in dogs.
crease in lactic and pyruvic acid and a subsequent de-
crease in pH.42 Theoretically, large transfusions could
produce clinical acidosis. As with citrate, however, pa- About the Authors
tients with normally functioning livers can convert Dr. Harrell is affiliated with the Department of Companion
these products to bicarbonate within hours of the trans- Animals and Special Species Medicine, College of Veteri-
fusion.19 Again, it is wise to be aware of this complica- nary Medicine, North Carolina State University, Raleigh,
tion if the patient has liver dysfunction. North Carolina. Dr. Kristensen is affiliated with Novo
Nordisk in Gentofte, Denmark, and is a Diplomate of the
Delayed Reactions American College of Veterinary Internal Medicine. Ms.
Disease Transmission Parrow is affiliated with the Department of Small Animal
Transmission of infectious disease is the most com- Medicine and Surgery, College of Veterinary Medicine,
mon cause of transfusion-related death in human University of Minnesota, St. Paul, Minnesota.
medicine.19 Transmission of HIV has accounted for
much of this mortality. Although no retrovirus has yet
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