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CE
Transfusion Medicine
Sarah Haldane, BVSc, MACVSc
Jennifer Roberts, DVM
Steven L. Marks, BVSc, MS, MRCVS, DACVIM
Marc R. Raffe, DVM, MS, DACVA, DACVECC
University of Illinois

ABSTRACT:
Transfusion therapy is indicated in patients with many different diseases and conditions,
including anemia, hemorrhage, coagulopathy, and hypoproteinemia. After whole blood is
collected from a donor animal, it may be administered immediately or fractionated into
its component parts (e.g., packed red blood cells, fresh-frozen plasma, cryoprecipitate,
platelet products).Transfusion reactions may manifest as complications of blood product
administration. However, selecting the appropriate blood product and carefully collecting,
storing, and handling blood, in combination with blood-typing and crossmatching, can
decrease the risk of transfusion reactions.

T
here are many indications for transfusion
therapy in veterinary practice, and with
the increased availability of blood prod-
ucts, it is becoming more widespread. Fraction-
ating whole blood into its component products
has made it easier to treat a broad range of con-
ditions when donors are not available. Blood
components accessible to veterinarians include
fresh and stored whole blood, packed red blood
cells (pRBCs), fresh-frozen plasma (FFP), cryo-
precipitate, and platelet products. However,
administering blood products is not a benign
procedure. Red blood cells (RBCs) are very
antigenic and can promote a significant immune
response. 1 Administering foreign proteins,
leukocytes, or platelets may also stimulate the
immune system.2 The appropriate blood product
should be selected based on maximum benefit
with minimum risk to the patient.
Email comments/questions to SELECTING BLOOD
compendium@medimedia.com, DONORS
fax 800-556-3288, or log on to Blood donors should be
www.VetLearn.com healthy adult (i.e., 2 to 8 years
of age) dogs and cats. Dogs should weigh more
than 66 lb (30 kg); have a packed cell volume
(PCV) of 40% or more; be fully vaccinated; and
be free of heartworm infection, brucellosis, and
tick-borne diseases (e.g., Ehrlichia canis, Babesia
canis, Rickettsia rickettsi, Borrelia burgdorferi
infections).3 It is also recommended that canine
donors test negative for dog erythrocyte antigen
(DEA) 1.1 (universal donors would also need
to test negative for DEA 1.2 and 7).4,5 Purebred
and crossbred Akitas have high levels of intra-
cellular potassium in their RBCs and should
not be used as blood donors.6
Cats should weigh more than 11 lb (5 kg), be
lean, and preferably be shorthaired. Feline
donors should have a PCV greater than 35%; be
fully vaccinated; and be free from FeLV, FIV,
Toxoplasma gondii, and Hemobartonella felis (now
called Mycoplasma hemofelis) infections. Cats
should be blood typed before blood collection.5,7
Withdrawal of 10% to 20% of the blood vol-
ume from a blood donor should not result in
clinically significant anemia. An 11-lb (5-kg)
cat may have 50 to 60 ml of blood collected in

COMPENDIUM 502 July 2004


one donation, whereas a 66-lb (30-kg) dog may have
450 ml of blood collected. Hypovolemia can result if
20% or more of the blood volume is withdrawn; if this
occurs, administering IV fluids is indicated. Blood
should not be collected more than once every 4 to 6
weeks.8
Canine Blood Groups
Nine blood groups (i.e., DEA 1.1, 1.2, 1.3, 3, 4, 5, 6,
7, 8) have been identified in dogs.9 The most clinically
significant are DEA 1.1 and 1.2.10 Spontaneously occur-
ring antibodies (i.e., alloantibodies) to these antigens
have not been identified; thus immunologic reactions
are rare for the first transfusion administered to dogs.
However, if a transfusion of blood positive for DEA 1.1
is administered to a recipient with blood negative for
DEA 1.1, antibody induction will occur. If a second
transfusion of blood positive for DEA 1.1 is adminis-
tered, an immune-mediated transfusion reaction may
destroy all transfused cells in less than 12 hours.9,10 Preg-
nancy can also induce alloantibodies to DEA 1.1 in up
to 25% of dogs.10
Alloantibodies against DEA 7 are present in up to
15% of dogs. These antibodies cause a delayed-type
immune response against RBCs positive for DEA 7,
resulting in hemolysis 1 to 3 days after transfusion.8,11
Delayed-type hemolytic reactions may also occur if the
donor animal has alloantibodies to DEA 3 or 5; how-
ever, these occur rarely in the general population.12
Feline Blood Groups
There are three feline blood types: A, B, and AB.
There is no universal donor group because cats with
type A blood have anti–type B antibodies and cats with
type B blood have anti–type A antibodies. 13 Type B
blood transfused into a cat with type A results in
hemolysis of transfused cells within 2 to 3 days. How-
ever, even a small amount of type A blood transfused
into a cat with type B blood results in acute hemolysis
and may be fatal.14 Therefore, crossmatching (see box on
this page) is essential for all feline blood transfusions.
Cats with type AB blood have been considered universal
recipients because they have no RBC alloantibodies in
their blood. However, if type B blood is transfused into
a recipient with type AB blood, the anti-A alloantibod-
ies present in the donor blood can cause a significant
transfusion reaction. Cats with type AB blood should be
transfused with type-specific blood, if available, or type
A blood if it is not.15
July 2004
Transfusion Medicine CE 503
Crossmatching a
• Collect serum and EDTA blood samples from the
donor and recipient (at least 1 ml in each sample).
• Separate the serum and RBCs into separate
labeled tubes.
• A whole-blood transfusion requires both a major
and minor crossmatch, whereas transfusion of
pRBCs requires only a major crossmatch.
Major Crossmatch
• Prepare a 3%–5% suspension of the washed donor
RBCs in saline.
— Pipette 0.1 ml of the pRBCs into 3 ml of 0.9%
NaCl.
— Centrifuge the sample for 1 min, remove the
supernatant, and resuspend the RBCs in 3 ml
of 0.9% NaCl.
— Repeat this three or four times to wash donor
cells. Following the last wash, there should be a
3%–5% suspension (3 ml total).
• Place two drops of the donor RBC suspension
into a clean, dry tube.
• Add two drops of the recipient serum to the same
tube.
• Centrifuge the serum for 30 sec at low speed.
• Check the sample for evidence of macroagglutination
or microscopic agglutination.
• If no agglutination is present, let the sample sit for
15 min at room temperature.
• Centrifuge the sample for 30 sec at low speed.
• Check the sample for evidence of macroagglutination
or microscopic agglutination.
Minor Crossmatch
• Prepare a 3%–5% suspension of the recipient
RBCs in 0.9% NaCl (as described above).
• Pipette two drops of the recipient RBC suspension
into a clean, dry tube.
• Add two drops of the donor’s serum to the same
tube.
• Centrifuge the sample immediately for 30 sec at
low speed.
• Check the sample for the presence of
macroagglutination or microscopic agglutination.
• If no agglutination is present, let the sample sit for
15 min at room temperature.
• Centrifuge the sample for 30 sec at low speed.
• Check the sample for the presence of
macroagglutination or microscopic agglutination.
a Modifiedwith permission from the University of Illinois
Standard Operating Procedure for Crossmatching.
COMPENDIUM
504 CE Transfusion Medicine
Blood-typing cards (Rapid Vet-H Feline blood-
typing cards, DMS Laboratories, Inc., Flemington, NJ)
are available for feline donors to discriminate among
types A, B, and AB (Figure 1). There are also canine
blood-typing cards (Rapid Vet-H Canine blood-typing
cards, DMS Laboratories, Inc.) that identify the pres-
ence or absence of DEA 1.1 on donor RBCs. These
Understanding transfusion component therapy allows
practitioners to match specific products with disease entities.
cards can be quickly and easily used and may be helpful
in emergencies.16 However, blood-typing cards should
not be considered a substitute for crossmatching.
PREPARING BLOOD COMPONENTS
Whole blood can be collected (usually into commer-
cially prepared blood bags) from donors via aseptic
venipuncture. Anticoagulants used for blood products
are citrate–phosphate–dextrose–adenine (CPDA-1) and
acid–citrate–dextrose (ACD). CPDA-1 has a shelf life
COMPENDIUM
of 35 days, and ACD has a shelf life of 21 days. Addi-
tive solutions can be used to preserve RBC function for
up to 42 days.17–19 Heparin has no preservative action,
and heparinized blood should be administered within 8
hours of collection.5
Units of fresh whole blood may be centrifuged and
fractionated into their component parts. RBCs precipi-
tate after centrifugation at 5000g for 5 minutes at 42.8˚F
(6˚C). The RBCs can then be separated from the plasma
fraction and stored at 33.8˚F to 42.8˚F (1˚C to 6˚C).20
Plasma can be rapidly frozen (within 6 hours of blood
collection) at –4˚F to –94˚F (–20˚C to –70˚C) for later
use as FFP.5 FFP contains albumin, globulins, and all
the coagulation factors, including the labile factors V
and VIII. The coagulation factors in FFP remain rela-
tively stable for up to 1 year, after which FFP is no
longer considered fresh but can be used as a source of
July 2004
 Transfusion Medicine CE 505

albumin and vitamin K–dependent clotting factors II,

VII, IX, and X.3,5
Cryoprecipitate is formed when FFP is briefly thawed
and recentrifuged at 39.2˚F (4˚C) and 5000g for 5 min-
utes. After separation, the precipitate should be rapidly
refrozen at –4˚F to –94˚F (–20˚C to –70˚C). Cryopre-
cipitate contains concentrated von Willebrand factor
(vWF), clotting factors VIII and XIII, and fibrinogen.
To prepare platelet-rich plasma, whole blood should
be centrifuged at room temperature and 2000g for 3
minutes. Additional centrifugation at 4000g for 6 min-
utes can be used to separate platelets from plasma to
produce a platelet-concentrated unit.5 Platelet products
prepared in this way should be administered as soon as
possible (ideally, within 8 to 12 hours of collection).5,21,22
Plateletpheresis involves removing whole blood from a
donor, separating the platelet fraction, and transfusing
the remaining blood components into the animal.5 This
technique is used in large blood-banking institutions to
prepare platelet concentrates, which can then be sus-
pended and frozen in dimethyl sulfoxide (DMSO) and
stored for 6 months.23,24

USING BLOOD COMPONENTS

Whole Blood
Fresh whole blood contains RBCs, serum proteins,
clotting factors, and platelets. When whole blood is
stored, the labile clotting factors V and VIII are
destroyed within 24 hours and platelets within 2 to 4
hours. Concentrations of 2,3-diphosphoglycerate (2,3-
DPG) progressively decline with storage,20 adversely
affecting the ability to unload oxygen into peripheral
tissues. However, human studies have shown that 2,3-
DPG in transfused blood regenerates to 50% of normal
levels within 7 hours of administration and reaches nor-
mal levels in 24 to 72 hours.25
Transfusing fresh or stored whole blood may be indi-
cated during acute hemorrhage or when multiple blood Figure 1. A blood-typing card showing a positive result
components are required.26 Animals with hemolytic (via agglutination) for type A feline blood. (Courtesy of dms
laboratories)
anemia or decreased production of RBCs often have
increased intravascular volume as a compensatory
response to decreased oxygen delivery to tissues.27 Vol-
ume overload may be a concern with whole blood trans- Packed Red Blood Cells
fusions in these patients. Ammonia levels increase while pRBCs have the advantage of containing the same
blood products are stored. It has been suggested that amount of RBCs, and therefore oxygen-carrying capac-
animals with liver disease should be transfused with ity, as a unit of whole blood, but in a significantly
products that have been stored for less than 2 weeks, smaller volume. The PCV of a unit of pRBCs may vary
although posttransfusion hyperammonemia in veteri- from 55% to 80% in dogs or 45% to 65% in cats,
nary patients has not been documented.28 depending on the PCV of the donor, diluting effects of

July 2004 COMPENDIUM

506 CE Transfusion Medicine
added preservatives, and amount of residual plasma vol-
ume in the bag. Some residual plasma is required to
provide a healthy environment for RBCs.29
pRBC transfusion is indicated in patients with ane-
mia caused by decreased erythropoiesis, hemolysis, or
blood loss. The smaller volume is also an advantage
when transfusing animals with concurrent cardiac or
renal compromise.30
Leukocytes
Leukocyte transfusion has not been shown to be benefi-
cial in critically ill veterinary patients.29 Leukocyte transfu-
sions are expensive and difficult because they must be har-
vested from the buffy coat layer of multiple units of blood.
Administering fractionated blood components
decreases the risk of transfusion reactions and volume
overload in critically ill patients.
Transfusing foreign leukocytes is unlikely to provide an
immune benefit to a recipient animal and may more likely
cause an immune reaction against the transfused cells.29
Plasma Products
The indications for using plasma products include
treating inherited and acquired factor deficiencies, treat-
ing coagulopathy, enhancing protective enzyme levels
(i.e., α1-antitrypsins, α2-macroglobulins), and augment-
ing intravascular colloid concentration.31
Coagulopathy
Liver failure or vitamin K deficiency (from either
cholestatic disease or vitamin K–antagonist ingestion)
may result in clinical coagulopathy.32,33 Patients that are
actively hemorrhaging benefit from immediate supple-
mentation of clotting factors in FFP. 34,35 Fresh and
stored whole blood also contain vitamin K–dependent
coagulation factors II, V, VII, and X and may be used if
an animal’s RBC count or PCV is decreased.
Disseminated intravascular coagulopathy (DIC) is a sec-
ondary syndrome characterized by hemostatic dysfunction.
Correcting the primary pathology is specific therapy for
DIC. Supportive therapy for patients with DIC includes
administering FFP to supplement clotting factors, anti-
thrombin, C-reactive protein (an acute-phase protein), and
fibronectin (a glycoprotein that aids cellular adhesion).3,32
COMPENDIUM
Dilutional coagulopathy may occur with acute massive
hemorrhage (e.g., trauma, hemoabdomen)36 or when
large volumes of fluids are rapidly administered during
resuscitation (e.g., shock). In these situations, immedi-
ately administering FFP may not be warranted unless
there is clinical evidence of hemorrhage; however, the
coagulation profile of patients with dilutional coagu-
lopathy should be monitored closely.
Transfusing specific coagulation factors for congenital
coagulation factor defects is not commonly performed in
veterinary medicine. The exception is using cryoprecipi-
tate for surgical prophylaxis or to treat active hemorrhage
in vWF- or factor VIII–deficient patients.37,38 FFP trans-
fusions do not predictably increase the concentration and
duration of activity of vWF and factor VIII; thus large
volumes of FFP may be required to control hemorrhage,
placing patients at risk for hypervolemia.37,38
Hypoproteinemia
Increased morbidity and mortality are well docu-
mented in humans with hypoalbuminemia (<2.5 g/dl)
compared with those with normal albumin levels, 39
although total proteins, rather than albumin alone, con-
tribute to colloid osmotic pressure.40 In chronic condi-
tions, FFP transfusions have only a transient effect on
albumin concentrations, and the volume of plasma
required to achieve a measurable increase in albumin is
quite large, placing patients at risk for volume over-
load.40 Because nutrition and colloid osmotic pressure
have the most influence on albumin synthesis, the most
effective way to increase long-term albumin concentra-
tions is with nutritional support.39,41 In the short term,
hypoproteinemic patients may benefit from a mild
increase in albumin from FFP in combination with
oncotic support from synthetic colloids.3
Pancreatitis
FFP transfusion has been advocated in treating pan-
creatitis to provide coagulation factors, maintain albu-
min concentrations, and supplement plasma protease
inhibitors (e.g., α2-macroglobulins, α1-antitrypsins).42
July 2004
510 CE Transfusion Medicine
However, human clinical trials have not shown consis-
tent improvement in morbidity and mortality when
FFP is administered to patients with pancreatitis.43,44
Antioxidant Properties
The primary mechanism whereby plasma has antioxi-
dant properties is through iron sequestration, which
limits the production of free hydroxyl radicals and pre-
vents subsequent cellular injury.45 There are no current
guidelines for FFP administration with regard to its
antioxidant effects.
Platelet Products
Platelets are extremely labile in serum and may be lost
from blood within a few hours of collection. Prophylactic
platelet transfusion is not recommended because platelet
products are difficult to store24 and transfused platelets
are not retained for long periods in circulation, especially
if the primary cause of thrombocytopenia is platelet
destruction.33 However, if platelet loss or dysfunction is
causing ongoing bleeding, transfusion of platelet-rich
plasma or platelet concentrates may be indicated.46,47
Platelet concentrates frozen in DMSO (canine frozen
platelet concentrate with 6% DMSO, Midwest Animal
Hemoglobin-based oxygen carriers can be used in
patients with acute hemorrhage and immune-mediated
anemia to reduce the risk of a transfusion reaction.
Blood Services, Stockbridge, MI) are available for use in
veterinary medicine. There have not been studies on the
efficacy of these products in veterinary patients.
Hemoglobin-Based Oxygen Substitutes
Hemoglobin-based oxygen carriers (HBOCs) have
been under investigation as a type of blood substitute,
principally to augment oxygen delivery to tissues. 48,49
Oxyglobin (hemoglobin glutamer–200 [bovine], Bio-
pure) is a purified, polymerized bovine hemoglobin
solution with an average hemoglobin concentration of
13 g/dl. It is considered a universally compatible blood
product because it lacks cell surface antigens and re-
duces the risk of contamination with infectious disease.
Bovine hemoglobin does not rely on 2,3-DPG for influ-
encing oxygen affinity; thus Oxyglobin has a lower oxy-
COMPENDIUM
gen tension (P50) at a given oxygen saturation than do
canine or feline RBCs and has enhanced carbon dioxide
and oxygen affinity. This leads to improved uptake and
transport at a given oxygen tension.49,50 Economically
appealing qualities include its long shelf life (i.e., 3
years), ability to be stored at room temperature, and
abundant supply.49
The oxygen-carrying effects of Oxyglobin last up to 3
days in circulation. However, in the absence of hemo-
lytic processes, transfused RBCs should remain in circu-
lation more than 28 days. Oxyglobin also has significant
colloidal properties,51 and patients should be monitored
for signs of volume overload during administration.
Adverse gastrointestinal effects have been reported.52
After infusion, patients can demonstrate transient dis-
coloration (i.e., yellow–orange, orange–brown) of their
mucous membranes and, less frequently, skin. Urine may
be similarly discolored, making interpretation of a urine
dipstick inaccurate. After administration, total hemo-
globin, rather than hematocrit, levels should be evalu-
ated. Depending on the dose administered, serum may
appear red-tinged or red–brown. This color change may
influence chemistry analyzers by causing interference
with colorimetric assays but does not alter noncolori-
metric tests, including most electrolyte panels, hemo-
grams, and coagulation assays.49,53 This effect is manu-
facturer and machine dependent and is discussed in
detail in the package insert.
The manufacturer’s recommended dose of Oxyglobin
is 10 to 30 ml/kg IV up to a maximum rate of 10
ml/kg/hr.54 In general, an initial dose of 10 ml/kg is rec-
ommended. Patients should be monitored because the
colloidal effects of Oxyglobin in circulation may lead to
decreased cardiac output, increased systemic vascular
resistance, and hemodilution.51,55 Oxyglobin is currently
not registered for use in cats but has been used as an
off-label product at a dose of 5 to 15 ml/kg IV at a rate
of 5 ml/kg/hr.56 Cats are prone to volume overload and
should be monitored closely during O xyglobin
infusion.56
July 2004
 Transfusion Medicine CE 511

Transfusion Rate ing calcium, such as lactated

Ringer’s solution, should not be
Example: A 44-lb (20-kg) dog with a PCV of 15% needs a pRBC transfusion. The
pRBCs have a PCV of 80%; the desired PCV for the dog is 28%. administered with blood prod-
ucts. Calcium deactivates the
Using the calculation: Using the guideline: citrate in the anticoagulant
Volume to be transfused: Desired PCV = 28% solution, possibly leading to
Desired PCV – Recipient PCV Recipient PCV = 15% thrombus formation. 29 Coad-
= kg × 90 ×
Donor PCV PCV must be raised by 13% ministering hypotonic or dex-
trose-containing fluids with
28 – 15 1 ml/kg of pRBC raises the PCV 1% blood products may result in
= 20 kg × 90 ×
80 13 ml/kg raises the PCV 13% hemolysis of RBCs and is
therefore not recommended.29
= 20 × 90 × 0.1625 Volume to be transfused:
= 13 × 20 kg All blood products should be
= 292.5 ml = 260 ml transfused within 4 hours to
reduce the risk of contamination
and bacterial colonization. 22,58
More rapid transfusion may be
ADMINISTERING BLOOD COMPONENTS indicated if there is ongoing blood loss or hypovolemia.
RBC products should be transfused to attain a PCV Care should be taken in patients with concurrent cardiac
8,29
of 25% to 30% in dogs or 20% in cats. This corre- or renal disease because of the risk of volume overload.29,32
sponds to results in human studies that do not recom- Plasma products should be thawed in a warm-water
mend transfusion above hemoglobin concentrations of 7 bath at 98.6˚F (37˚C) before transfusion. The access
to 10 g/dl (PCV: 21% to 30%), depending on a patient’s ports in the bag should be covered with plastic to avoid
27,57
clinical status. The volume of whole blood or pRBC contamination with water. Plasma products should be
required can be calculated using the following equation: administered through a dedicated IV line with a 170-
Volume to be transfused (ml) = µm filter. Once FFP has been thawed, it should be used
within 4 hours because the labile clotting factors deteri-
90 (Dogs) Desired PCV – Recipient PCV orate quickly and there is increased risk of subsequent
kg × or ×
Donor PCV bacterial contamination. The recommended starting
70 (Cats)
dose for FFP is 6 to 10 ml/kg3,29,31 (Table 1). Plasma
As a guideline, 2 ml/kg of whole blood raises the infusion should continue in coagulopathic patients until
PCV 1% (therefore, 20 ml/kg raises the PCV 10%). For hemorrhage is controlled or clotting times are within
pRBC, 1 ml/kg raises the PCV 1% (therefore, 10 ml/kg 1.5 times the upper limit of normal. A dose of 45 ml/kg
raises the PCV 10%)29 (see box on this page). These is required to raise the albumin concentration 1 g/dl in
general guidelines depend on the PCV of the donor hypoproteinemic patients,3 thus making FFP adminis-
blood and may underestimate the amount of blood tration for hypoalbuminemia generally unfeasible.
required for transfusion. In cases of known canine von Willebrand’s disease,
It is not necessary to warm pRBC or stored whole administering cryoprecipitate is recommended at an ini-
blood before transfusion, except for very small or pedi- tial dose of 1 unit/10 kg before a surgical procedure or
32
atric patients, which are at greater risk of hypothermia. as needed to stop ongoing hemorrhage.33,38
Blood products should not be warmed to higher than Platelet-rich plasma should be administered within 12
98.6˚F (37˚C) because this leads to hemolysis of cells, hours of collection at a dose of 1 unit/3 kg. Platelet concen-
precipitation of fibrinogen, and degradation of serum trates frozen in DMSO should be allowed to thaw at room
22
coagulation factors and proteins. temperature, with gentle mixing every 5 minutes. The ini-
Blood products should be administered via a dedi- tial dose of platelet concentrate should be 1 unit/10 kg.33
cated IV fluid line or in combination with 0.9% sodium
chloride (NaCl). The line should always contain a 170- TRANSFUSION REACTIONS
µm filter. pRBCs, in particular, may require dilution Transfusion reactions can be classified as immuno-
with fluids to facilitate administration. Fluids contain- logic or nonimmunologic. Acute immunologic reactions

July 2004 COMPENDIUM

512 CE Transfusion Medicine

Table 1. Blood Products: Indications for Use and Doses

Product Indications Infusion Rate Comments
Fresh whole blood Anemia 2 ml/kg to raise Risk of volume overload when
Hemorrhage PCV 1% administered to normovolemic
Coagulopathy patients
Stored whole blood Anemia 2 ml/kg to raise Loss of labile clotting factors V
Hemorrhage PCV 1% and VIII as well as platelets
pRBCs Anemia 1 ml/kg to raise Useful in patients with low
Hemorrhage PCV 1% PCV and normal total protein
Platelet concentrate Thrombocytopenia with 1 unit/10 kg Platelet transfusions have variable
active hemorrhage (as needed to efficacy in recipient animals
stop hemorrhage)
Platelet-rich plasma Thrombocytopenia 1 unit/3 kg All clotting factors and platelets
Coagulopathy present
Risk of volume overload in
normovolemic patients
FFP Antiprotease or antioxidant Coagulopathy: Multiple infusions may be needed
activity 6–10 ml/kg because of the short half-life of
Coagulopathy (as needed to the clotting factors
Hypoproteinemia stop hemorrhage)
Hypoalbuminemia:
45 ml/kg
Cryoprecipitate von Willebrand’s disease 1 unit/10 kg Administer 30 min before surgery
Hemophilia A
Hypofibrinogenemia
Oxyglobin Anemia Dogs: 10–20 ml/kg Monitor for volume overload
Shock Cats: 5–10 ml/kg Monitor hemoglobin levels, rather
than PCV, after transfusion

usually occur within the first 1 to 2 hours of transfusion
but can be seen up to 48 hours later.4,14 Common clini-
cal signs are listed in Table 2. Acute hemolysis can also
be seen if incompatible blood is administered, and this
reaction can be life threatening.4,9
Fever is a common acute transfusion reaction that is
usually transient and does not require treatment. 4,7
However, fever may also indicate acute hemolysis or
bacterial contamination of the blood product, both of
which require prompt intervention. Evaluating the
blood bag for evidence of infection is warranted. Vomit-
ing, diarrhea, abdominal pain, hypotensive shock, or
DIC may develop with bacterial contamination.4
Delayed immunologic reactions usually involve
hemolysis and shorten the life span of transfused RBCs.
The normal life span of a transfused RBC is 21 to 48
days. A delayed transfusion reaction may result in an
RBC life span of 2 to 5 days.30
Nonimmunologic reactions occur because of either
changes in blood products during storage or administer-
ing excessive volumes or rates of fluids 4 (Table 2).
Changes in blood products may include hyperammone-
mia, 28 hypophosphatemia, hyperkalemia, 59 bacterial
contamination, or clot formation within the unit. Circu-
latory (volume) overload, erythrocytosis, or hyper-
proteinemia are also possible complications of blood
product transfusion.4 Massive transfusions (greater than
one blood volume) can lead to dilutional coagulopathy
(thrombocytopenia and prolonged coagulation times) or
cause citrate intoxication, which leads to clinical signs of
hypocalcemia or hypomagnesemia.60
Preventing Transfusion Reactions
Preventing transfusion reactions begins with screening
blood donor animals and aseptically collecting and
administering blood products. For cats, recipient blood
should always be crossmatched with donor blood before
a transfusion.7 Dogs that have had a previous transfu-
(text continues on p. 516)

COMPENDIUM July 2004

 Transfusion Medicine CE 513

Table 2. Transfusion Reactions

Transfusion Reaction Clinical Signs Treatment
Anaphylactic shock Collapse Stop the transfusion, administer epinephrine and
Respiratory and/or corticosteroids, and commence CPCR.
cardiac arrest

Type 1 hypersensitivity Tachypnea Stop the transfusion, administer corticosteroids and/or

Fever antihistamines, and restart the transfusion at a slower rate.
Cardiac arrhythmia
Vomiting
Urticaria
Pruritus
Angioedema
Erythema
Vomiting

Acute hemolysis Tachypnea Stop the transfusion and administer corticosteroids and
Fever IV fluids with or without vasopressor to maintain arterial
Hemoglobinemia blood pressure.
Hemoglobinuria
Collapse
Shock

Microbial infection Tachypnea Stop the transfusion and remove all contaminated lines
Tachycardia and catheters, collect donor blood sample and recipient
Fever blood and urine samples for culture, and administer
Vomiting systemic antibiotics and IV fluids to maintain blood
Shock pressure.
Collapse

Citrate overdose Hypocalcemia: Administer 10% calcium gluconate (1 ml/kg slow IV), and
Tremors monitor the ECG.
Fever
Cardiac arrhythmia
Vomiting
Seizures
Hypomagnesemia: Add magnesium sulfate (0.75–1 mEq/kg/day) to IV
Cardiac arrhythmia fluids.
Muscle weakness

Hypothermia Depression Stop the transfusion, administer warm blood products,

Shivering and begin active external warming of the patient.
Low temperature

Circulatory overload
Tachypnea Stop the transfusion; administer diuretics with or without
Normal to low heart rate vasodilators; and restart the transfusion at a lower rate, if
Increased central appropriate, or use a different blood product (e.g., pRBCs
venous pressure rather than whole blood).
Pulmonary edema

Hyperkalemia Bradycardia Stop the transfusion, administer 0.9% NaCl IV for

Cardiac arrhythmia diuresis, and administer dextrose (0.5 g/kg) with insulin
ECG changes (0.01 units/kg).
CPCR = cardiopulmonary cerebral resuscitation; ECG = electrocardiogram.

July 2004 COMPENDIUM

516 CE Transfusion Medicine

sion or pregnancy also require crossmatching.10 Before transfusion, blood

products should be examined for changes in color or consistency that may
indicate hemolysis, clotting, or microbial infection. Transfusions should be
started at half the calculated rate for 15 minutes, and animals should be
constantly monitored for signs of tachypnea, increased heart rate, fever,
urticaria, or vomiting.8 Once the administration rate increases, animals
should be monitored every 15 to 30 minutes for signs of transfusion reac-
tions. Some authors recommend administering an antihistamine before any
transfusion to prevent type 1 hypersensitivity reactions.4,29

Managing Transfusion Reactions

If signs of acute transfusion reaction are detected, the transfusion should
be stopped immediately and crystalloid fluids infused to maintain blood
pressure, heart rate, and diuresis4 (Table 2). If the reaction is mild, the trans-
fusion may be restarted at a lower rate and the animal monitored closely for
progression of clinical signs.4

REFERENCES
1. Garratty G, Telen MJ, Petz LD: Red cell antigens as functional molecules and obstacles to transfusion.
Hematology (Am Soc Hematol Educ Prog):445–462, 2002.
2. Anniss AM, Sparrow RL: Expression of CD47 (integrin-associated protein) decreases on red blood cells
during storage. Transfus Apheresis Sci 27:233–238, 2002.
3. Wardrop KJ: Canine plasma therapy. Vet Forum 4:36–40, 1997.
4. Harrell KA, Kristensen AT: Canine transfusion reactions and their management. Vet Clin North Am Small
Anim Pract 25:1333–1364, 1995.
5. Authement JM: Preparation of components. Adv Vet Sci Comp Med 36:171–185, 1991.
6. Degen M: Pseudohyperkalemia in Akitas. JAVMA 190:541–543, 1987.
7. Griot-Wenk ME, Giger U: Feline transfusion medicine. Blood types and their clinical importance. Vet
Clin North Am Small Anim Pract 25:1305–1322, 1995.
8. Mackin A: Transfusion therapy in practice, in Sydney Post Graduate Foundation: Problems in Internal
Medicine. Proc 346:73–93, 2002.
9. Giger U, Gelens CJ, Callan MB, et al: An acute hemolytic transfusion reaction caused by dog erythrocyte
antigen 1.1 incompatibility in a previously sensitized dog. JAVMA 206:1358–1362, 1995.
10. Young LE, O’Brien WA, Swisher SN, et al: Blood groups in dogs: Their significance to the veterinarian.
Am J Vet Res 13:207–213, 1952.
11. Callan MB, Jones LT, Giger U: Hemolytic transfusion reactions in a dog with an alloantibody to a com-
mon antigen. J Vet Intern Med 9:277–279, 1995.
12. Swisher SN, Young LE: The blood group system of dogs. Physiol Rev 14:3, 1961.
13. Auer L, Bell K: The AB blood group system of cats. Anim Blood Groups Biochem Genet 12:287–297, 1981.
14. Giger U, Bucheler J: Transfusion of type-A and type-B blood to cats. JAVMA 198:411–418, 1991.
15. Knottenbelt CM: The feline AB blood group system and its importance in transfusion medicine. J Fel Med
Surg 4:69–76, 2002.
16. Feldman BF: In-house canine and feline blood typing. JAAHA 35:455–456, 1999.
17. Hogman CF, Knutson F, Loof H, et al: Improved maintenance of 2,3-DPG and ATP in RBCs stored in a
modified additive solution. Transfusion 42:824–829, 2002.
18. Wardrop KJ, Owen TJ, Meyers KM: Evaluation of an additive solution for preservation of canine red
blood cells. J Vet Intern Med 8:253–257, 1994.
19. Wardrop KJ, Young J, Wilson E: An in vitro evaluation of storage media for the preservation of canine
packed red blood cells. Vet Clin Pathol 23:83–88, 1994.
20. Hogman CF, Knutson F, Loof H: Storage of whole blood before separation: The effect of temperature on
red cell 2,3-DPG and the accumulation of lactate. Transfusion 39:492–497, 1999.
21. Abrams-Ogg ACG, Kruth SA, Carter RF, et al: Preparation and transfusion of canine platelet concen-
trates. Am J Vet Res 54:635–642, 1993.
22. Mooney S: Preparation of blood components. Prob Vet Med 4:594–599, 1992.
23. Allyson K, Abrams-Ogg ACG, Johnstone IB: Room temperature storage and cryopreservation of canine
platelet concentrates. Am J Vet Res 58:1338–1347, 1997.
24. Murphy S, Sayar SN, Abdou NL, et al: Platelet preservation by freezing. Use of dimethylsulfoxide as cry-
oprotective agent. Transfusion 14:139–144, 1974.
25. Heaton A, Keegan T, Holme S: In vivo regeneration of red cell 2,3-diphosphoglycerate following transfu-
sion of DPG-depleted AS-1, AS-3 and CPDA-1 red cells. Br J Haematol 71:131–136, 1989.

COMPENDIUM July 2004


26. Laine E, Steadman R, Calhoun L, et al: Comparison of RBCs and FFP with
whole blood during liver transplant surgery. Transfusion 43:322–327, 2003.
27. American Society of Anesthesiologists: Practice guidelines for blood compo-
nent therapy. Anesthesiology 84:732–747, 1996.
28. Waddell LS, Holt DE, Hughes D, et al: The effect of storage on ammonia
concentration in canine packed red blood cells. J Vet Emerg Crit Care
11:23–26, 2001.
29. Kristensen AT, Feldman BF: General principles of small animal blood compo-
nent administration. Vet Clin North Am Small Anim Pract 25:1277–1290, 1995.
30. Kerl ME, Hohenhaus AE: Packed red blood cell transfusions in dogs: 131
cases (1989). JAVMA 202:1495–1499, 1993.
31. Logan JC, Callan MB, Drew K, et al: Clinical indications for use of fresh
frozen plasma in dogs: 74 dogs (October through December 1999). JAVMA
218:1449–1455, 2001.
32. Cotter SM: Clinical transfusion medicine. Adv Vet Sci Comp Med 36:187–
223, 1991.
33. College of American Pathologists: Practice parameter for the use of fresh-
frozen plasma, cryoprecipitate and platelets. JAMA 271:777–781, 1994.
34. Sheafor SE, Couto CG: Clinical approach to a dog with anticoagulant
rodenticide poisoning. Vet Med 94:466–471, 1999.
35. Kaul VV, Munoz SJ: Coagulopathy of liver disease. Curr Treat Options Gas-
troenterol 3:433–438, 2000.
36. Lewis DC, Bruyette DS, Kellerman DL, et al: Thrombocytopenia in dogs
with anticoagulant rodenticide-induced hemorrhage: Eight cases (1990–
1995). JAAHA 33:417–422, 1997.
37. Stokol T, Parry B: Efficacy of fresh-frozen plasma and cryoprecipitate in dogs
with von Willebrand’s disease or hemophilia A. J Vet Intern Med 12:84–92,
1998.
38. Meyers KM, Wardrop KJ, Meinkoth J: Canine von Willebrand’s disease:
Pathobiology, diagnosis and short-term treatment. Compend Contin Educ
Pract Vet 14:13–22, 1992.
39. Kaminski Jr MV, Williams SD: Review of the rapid normalization of serum
albumin with modified total parenteral nutrition solutions. Crit Care Med
18:327–335, 1990.
Transfusion Medicine CE 517
40. Kaminski Jr MV, Haase TJ: Albumin and colloid osmotic pressure implica-
tions for fluid resuscitation. Crit Care Clin 8:311–321, 1992.
41. Center SA: Pathophysiology of liver disease: Normal and abnormal function,
in Guilford WG, Center SA, Strombeck DR, et al (eds): Strombeck’s Small
Animal Gastroenterology. Philadelphia, WB Saunders, 1996, pp 553–632.
42. Cuschieri A, Wood RA, Cumming JR, et al: Treatment of acute pancreatitis
with fresh frozen plasma. Br J Surg 70:710–712, 1983.
43. Goodman AJ, Bird NC, Jognson AG: Antiprotease capacity in acute pancre-
atitis. Br J Surg 73:796–798, 1986.
44. Leese T, Holliday M, Heath D, et al: Multicentre trial of low volume fresh
frozen plasma therapy in acute pancreatitis. Br J Surg 74:907–911, 1987.
45. Marino PL: Oxidant injury, in Wingfield WE, Raffe MR (eds): The Veteri-
nary ICU Book. Jackson, WY, Teton NewMedia, 2002, pp 24–39.
46. Schlossberg HR, Herman JH: Platelet dosing. Transfus Apheresis Sci 28:221–
226, 2003.
47. Rebulla P: Revisitation of the clinical indications for the transfusion of
platelet concentrates. Rev Clin Exp Hematol 5:288–310, 2001.
48. Moore EE: Blood substitutes: The future is now. J Am Coll Surg 196:1–17,
2003.
49. Hughes Jr GS, Francome SF, Antal EJ, et al: Hematologic effects of a novel
hemoglobin-based oxygen carrier in normal male and female subjects. J Lab
Clin Med 126:444–451, 1995.
50. Muir WW, Wellman ML: Hemoglobin solutions and tissue oxygenation. J
Vet Intern Med 17:127–135, 2003.
51. Driessen B, Jahr JS, Lurie F, et al: Arterial oxygenation and oxygen delivery
after hemoglobin-based oxygen carrier infusion in canine hypovolemic shock:
A dose response study. Crit Care Med 31:1771–1779, 2003.
52. Rentko VT, Wohl JS, Murtagh R, et al: A clinical trial of hemoglobin-based
oxygen carrying (HBOC) fluid in the treatment of anemia [abstract]. 14th
Annual ACVIM Forum:177, 1996.
53. Callas DD, Clark TL, Moreira PL, et al: In vitro effects of a novel hemoglo-
bin-based oxygen carrier on routine chemistry, therapeutic drug, coagulation,
hematology, and blood bank assays. Clin Chem 43:1744–1748, 1997.
518 CE Transfusion Medicine

54. Food and Drug Administration 21CFR522.1125: Hemoglobin glutamer-200 d. Crossmatching is not required for the first transfu-
(bovine). 63 Federal Register 11598 10:1998. sion to any cat but is mandatory for all subsequent
55. Driessen B, Jahr JS, Lurie F, et al: Inadequacy of low-volume resuscitation
with hemoglobin-based oxygen carrier hemoglobin-200 (bovine) in canine transfusions.
hypovolemia. J Vet Pharmacol Ther 24:61–71, 2001.
56. Gibson GR, Callan MB, Hoffman V, et al: Use of a hemoglobin-based oxygen- 4. An 11-lb (5-kg) cat with a PCV of 15% will
carrying solution in cats: 72 cases (1998–2000). JAVMA 221:96–102, 2002. receive a transfusion of pRBCs with a PCV of
57. Hebert PC, Wells G, Marshall J, et al: Transfusion requirements in critical 55%. A transfusion rate of ___ ml/hr will most
care. JAMA 273:1439–1444, 1995.
likely increase the PCV by 10% in 4 hours.
58. Widmann FK: American Association of Blood Banks Technical Manual, ed 9.
Arlington, VA, American Association of Blood Banks, 1985. a. 10 c. 20
59. Price GS, Armstrong PJ, McLeod DA, et al: Evaluation of citrate–phos- b. 15 d. 30
phate–dextrose–adenine as a storage medium for packed canine erythrocytes.
J Vet Intern Med 2:126–132, 1988. 5. Which statement about Oxyglobin is incorrect?
60. Jutkowitz LA, Rozanski EA, Moreau JA, et al: Massive transfusion in dogs. a. Oxyglobin is a purified, polymerized, equine hemoglo-
JAVMA 220:1664–1669, 2002.
bin solution.
b. Oxyglobin is less likely to cause transfusion reactions
than are RBC products.
ARTICLE #1 CE TEST
This article qualifies for 1.5 contact hours of continuing CE c. Administering excessive Oxyglobin may lead to vol-
ume overload resulting from its colloidal properties.
education credit from the Auburn University College of d. Oxyglobin transfusion commonly causes skin and
Veterinary Medicine. Subscribers who wish to apply this serum discoloration, which may affect blood chem-
credit to fulfill state relicensure requirements should consult istry results.
their respective state authorities regarding the applicability
of this program. To participate, fill out the test form inserted 6. Which statement about platelet products is
at the end of this issue.To take CE tests online and get real- incorrect?
time scores, log on to www.VetLearn.com. a. Platelets should be rapidly collected and stored after
blood donation.
1. Which statement about blood donors is incorrect? b. Platelets should be transfused to thrombocytopenic
a. Dogs should be healthy adults and test negative for animals only if they have ongoing hemorrhage.
DEA 1.1. c. Platelet concentrates can be stored frozen in DMSO
b. Cats should be screened for retroviral, T. gondii, and for up to 6 months.
M. hemofelis infections before donating blood. d. Transfused platelets last for long periods in recipient
c. Purebred Akitas should not be used for blood dona- animals.
tions because of the high level of potassium in their
RBCs. 7. Which condition is not a sign of type 1 hypersen-
sitivity reactions?
d. Blood-donor dogs should weigh more than 66 lb (30
a. thrombocytopenia c. vomiting
kg) and have a PCV greater than 45%.
b. urticaria d. cardiac arrhythmia
2. Which statement regarding 2,3-DPG is incorrect?
8. For which condition is an FFP transfusion not
a. 2,3-DPG is required to unload oxygen from hemo-
indicated?
globin into peripheral tissues.
a. DIC
b. 2,3-DPG levels decline with storage of RBC products. b. vitamin K–antagonist intoxication
c. 2,3-DPG levels return to normal in transfused RBCs c. immune-mediated thrombocytopenia
within 7 hours of administration. d. fulminant liver failure
d. Oxyglobin contains bovine hemoglobin, which does
not rely on 2,3-DPG for oxygen affinity. 9. For which condition is a cryoprecipitate transfu-
sion indicated?
3. Which statement regarding feline blood types is a. von Willebrand’s disease
correct? b. hemophilia A (factor VIII deficiency)
a. Because they have no alloantibodies in their blood, c. hemophilia B (factor IX deficiency)
cats with type AB blood can be used as universal d. a and b
donors.
b. Type A blood transfused into a cat with type B blood 10. Which condition is not a delayed-type transfu-
results in hemolysis of RBCs within 2 to 3 days. sion reaction?
c. Cats with type AB blood should be transfused with a. hypocalcemia c. hyperammonemia
type A blood if type-specific blood is not available. b. hypokalemia d. pulmonary edema

COMPENDIUM July 2004