Resident Version
Blood Transfusion Reactions Module
created by Dr. Fraz Harji and Dr. Debra Novak
Updated 5/2009
Objectives:
By the end of this module, you should be able to:
1. Know the different risk factors involved in transfusions and its frequency
2. Recognize the major types of immunologic reactions to blood transfusion.
3. Know how to approach a patient with a transfusion reaction and initial
management.
4. Differentiate between benign and severe reactions.
Reference:
1. Tierney, Lawrence, McPhee, Stephen J., Papadakis, Maxine A. Current
Medical Diagnosis and Treatment.
2. Goodnough L. T., Brecher M. E., Kanter M. H., AuBuchon J. P, Medical
Progress: Transfusion Medicine — Blood Transfusion— First of Two Parts.
N Engl J Med 1999; 340:438-447, Feb 11, 1999.
3. Up-to-date online. Accessed 3/2007.
RISKS OF BLOOD TRANSFUSION
RISK FACTOR
ESTIMATED FREQUENCY (per actual
unit)
Viral Infection
Hepatitis A
1/1,000,000
Hepatitis B
1/30,000 – 1/250,000
Hepatitis C
1/30,000 – 1/150,000
HIV
1/200,000 – 1/2,000,000
Bacterial Contamination
Red Cells
1/500,000
Platelets
1/12,000
Acute hemolytic reactions
1/250,000 – 1/1,000,000
Delayed hemolytic reactions
1/1,000
Transfusion-related acute lung Injury
1/2,000 – 1/5,000
Severe anaphylactic reactions
1/20,000 – 1/50,000
Contamination of Red Cells

Most commonly implicated is Yersinia enterocolitica, and other gram-negative
organisms

Directly related to the length of storage of blood units
Contamination of Platelets

Platelet transfusion from multiple pooled donor platelets has greater risk of
infection compared to platelet unit from single donor

Related to bacterial overgrowth with time, shorter shelf life compared to red cells

Most commonly implicated are Staph. aureus, Klebsiella pnemoniae, Serratia
marcescens, and Staph. epidermidis
Transfusion-Mediated Immunomodulation

Immunosuppressive effect of blood transfusion is related to exposure to
leukocytes in donor blood

Clinically important in patients undergoing renal transplantation and in women
with multiple miscarriages

Immunosuppressive effects of blood transfusion remains controversial
Major Immunologic Reactions

Immunologic blood transfusion reactions results from interactions between
antibodies (inherited or acquired) with antigens associated with transfused blood
products

Initial symptoms of reactions with serious or benign consequences are often
similar
Febrile, nonhemolytic transfusion reaction

Most common transfusion reaction and it is benign

Commonly caused by cytokines which are generated and accumulate during the
storage of blood components

Symptoms include fever, chill, and sometimes mild dyspnea within one to six
hours after transfusion of red cells or platelets

Management includes stopping the transfusion and determining that a hemolytic
reaction is not taking place; Send the red cell bag back to blood bank for repeat
typing and cross-matching
Acute hemolytic transfusion reaction

It is a medical emergency

Usually due to ABO incompatibility, most often the result of clerical or
procedural error

Fever and chills may be the only manifestations. The classic presenting triad of
fever, flank pain, and red or brown urine (ie, hemoglobinuria) is rarely seen

There is a rapid destruction of donor erythrocytes by preformed recipient
antibodies which may lead to disseminated intravascular coagulation (DIC),
hypotension, shock, and acute renal failure due to acute tubular necrosis

Management includes stopping the transfusion and determining that a hemolytic
reaction is taking place

If there are any clues that acute hemolytic reaction is taking place, ie pink urine,
flank pain, decreased urine output, hypotension, or identified clerical error, then
normal saline needs to be started immediately to maintain good urine output and
adequate blood pressure. Avoid Lactated Ringer’s solution or dextrose solution as
these may react with the remaining blood in the tubing. A vasopressor may be
required.

If massive hemolysis has occurred, then hyperkalemia is likely. Place patient on
telemetry and monitor chemistries and renal function as acute hemodialysis may
be required. Coags should also be monitored.

The blood bank should be alerted immediately, since if blood samples or blood
bags have been switched in error, there may be a second patient at risk for a
similar event.

Please note that with acute hemolysis, only hemoglobenemia will be present at
first and transiently. Hemoglobenemia will turn the plasma pink. As free
hemoglobin is released into plasma, haptoglobin binds and clears it, and therefore
haptoglobin may be depressed in hemolysis. If the haptoglobin-binding capacity
of the plasma is exceeded, free hemoglobin passes through the glomerulus and it
is reabsorbed by tubular cells. Hemoglobinuria will be present only when the
capacity for reabsorption of hemoglobin by the kidney is exceeded.

The excess heme from hemoglobin will be converted to biliverdin and then
bilirubin, eventually leading to increased indirect bilirubin. The end result will be
failure of the hematocrit to rise by the expected amount.
Delayed hemolytic transfusion reactions

Generally seen within 2 to 10 days after transfusion

Due to minor red-cell antigens re-exposure. These antigens are not detected by a
routine antibody assay before transfusion, ie Kidd or Rh. These minor antigens
may have been encountered previously by transfusion, transplantation, or
pregnancy.

Hemolysis is usually extravascular and less severe than with acute reactions

Suspect this when you see falling hematocrit and slight fever days after the
transfusion. Mild increase in indirect bilirubin and spherocytosis on blood smear
may be noted.

No treatment is required if there is no brisk hemolysis. However it is important to
make the diagnosis so the patient may be informed of the antigen and future
transfusions containing the antigen be avoided.
Anaphylactic Reactions

It is a life-threatening reaction

It occurs within a few seconds to a few minutes after the start of a transfusion

Manifested by hypotension, angioedema, respiratory distress and shock

It is due to the presence of class-specific IgG, anti-IgA antibodies in patients who
are IgA deficient. Selective IgA deficiency is not uncommon, occurring in about 1
in 300 to 500 people. Fortunately, not all IgA deficient patients have developed
antibodies.

Management includes stopping the transfusion, Epinephrine, 0.3 IM
intramuscularly, possibly intravenous epinephrine drip, maintenance of airway,
and volume resuscitation and vasopressors if needed

It is important to make the diagnosis so that the next time patient receives
transfusion, it is either IgA-deficient blood products or extra-washed red cells or
platelet products
Urticarial transfusion reactions

Usually benign, only rarely does it present as first sign of more serious reaction

Due to soluble allergenic substances in the plasma of the donated blood product
react with preexisting IgE antibodies in the recipient. This causes mast cells and
basophils to release histamine, leading to hives or urticaria.

Management includes stopping the transfusion, using 25–50mg of Benadryl
IV/PO if urticaria is extensive

If urticaria decreases and there are no other evidence of more serious reaction, ie
dyspnea, angioedema, hypotension, or anaphylaxis, transfusion may be continued
Transfusion- related acute lung injury (TRALI)

It can range from benign to life threatening

It occurs within two to four hours after the start of a transfusion

Characterized by fever, cough, pulmonary edema, acute respiratory distress,
hypoxemia, and hypotension

It may look identical to acute respiratory distress syndrome (ARDS), but carries a
better prognosis and usually full recovery is within 96 hours of onset

Management is supportive
Post-transfusion purpura

Primarily seen in women

It occurs 5 to 10 days following transfusion

Manifested by severe thrombocytopenia, lasting days to weeks

It may be confused with drug-induced or idiopathic thrombocytopenic purpura,
since the blood and bone marrow smears are appear the same.

Preferred therapy is intravenous immune globulin (IVIG) since onset of action is
faster; other alternatives include high dose steroids or exchange transfusion,
although they can take weeks to work
CASE:
1. A nurse on Medicine Ward calls you regarding a 68 year old male with colon
cancer who is getting a transfusion of 2 units of packed red blood cells (PRBCs).
One hour into the first unit, his temperature increases from 37.5 to 39.0 degrees
Celsius. The patient has no other complaints, and his vital signs are otherwise
stable.
a. What do you tell the nurse?
b. Is this a benign blood transfusion reaction or life threatening?
c. What is the differential diagnosis?
d. Should a transfusion reaction workup be done?
e. What is the most common transfusion reaction?
f. What is the most common cause of acute hemolytic transfusion reaction?
g. How should you manage the patient?
Review Questions:
1. A 33-year-old white man presents with an exacerbation of Crohn disease, which
is manifested by bright red blood from the rectum, abdominal pain and anemia.
You begin therapy for exacerbation of Crohn disease, and you also order that
transfusion of 3 units of red blood cells. Approximately 30 minutes after the first
unit of red cells is begun, the nurse calls and says the patient has a fever and
“doesn’t feel well”.
Which of the following statements regarding transfusion complications is true?
A. Immediate hemolytic reactions are the result of an amnestic response to an
antigen to which the recipient is already sensitized
B. Delayed hemolytic reactions occur during primary sensitization and can be as
severe as immediate hemolytic reactions
C. Until the cause of the hemolytic transfusion reaction is identified, the patient may
only receive type O red cells or AB plasma
D. Fever without signs of hemolysis can be managed with acetaminophen; no further
laboratory workup is necessary
Concept: To understand the potential complications of transfusions
Answer: C
Hemolytic transfusion reactions are classified as immediate or delayed, depending on
their pathophysiology. Immediate hemolytic reactions are the result of a preexisting
antibody in the recipient that was not detected during pre-transfusion testing.
Delayed hemolytic reactions are the result of an amnestic response to an antigen to
which the recipient is already sensitized. Clinical evidence of hemolysis is likely to
be more severe in immediate hemolytic reactions and include back pain, pain along
the vein into which the blood is being transfused, changes in vital signs, evidence of
acute renal failure, and signs of developing disseminated intravascular coagulation.
Until the antibody causing the immune hemolysis is identified, only type O red cells
and AB plasma should be used. Febrile reactions are characterized by the
development of fever during transfusion or within 5 hours after transfusion. The
differential diagnosis for a patient undergoing a non-hemolytic febrile transfusion
reaction should always include unrecognized sepsis. When febrile reaction is
suspected, immediate management consists of discontinuing the transfusion,
obtaining appropriate cultures, and returning the product to the blood bank.
2. A 65-year-old man presents to you for preoperative workup before undergoing
aortic valve replacement for aortic regurgitation (indicated because of progressive
left ventricular dysfunction, as revealed on echocardiogram) and coronary artery
bypass surgery. He is interested in autologous blood donation. He has had
chronic stable anginal for the past 2 years, which is brought on by maximal
exertion; his anginal has remained unchanged for 1 year. For the past 2 days he
has had increased urgency for urination and dysuria. On physical examination, he
has a 2/4 diastolic murmur and suprapubic tenderness; otherwise, his examination
is normal.
What absolute contraindication to autologous blood donation does this man have?
A.
B.
C.
D.
Angina
Aortic regurgitation
Active bacterial infection
Age older than 60 years
Concept: To know the absolute contraindications to autologous blood donation
Answer: C
This patient appears to have a UTI, so he cannot donate blood until that is resolved.
Active bacterial infection is one of the three absolute contraindications to autologous
blood donation; the other two are tight aortic stenosis and unstable angina. Although this
man’s stable angina might temper one’s willingness to recommend autologous blood
donation (especially because the risk of disease transmission in donated blood is low
enough to make potential clerical error in the transfusion of autologous blood more of a
concern) it is not an absolute contraindication, nor is aortic regurgitation or his age.
3. Which of the following patients absolutely requires platelet transfusion?
A. A patient who has been taking aspirin for a headache and who is now scheduled
for emergent evacuation of his subdural hemorrhage; platelet count, 100,000
B. A patient with idiopathic thrombocytopenia; platelet count, 10,000
C. A patient with thrombotic thrombocytopenic purpura; platelet count, 9,000
D. A patient with end-stage liver disease who is complaining of easy bruising;
platelet count, 50,000
Concept: To know the indications for platelet transfusion
Answer: A
Although a platelet count of 100,000 is adequate for major surgery, because of this
patient’s use of aspirin, those platelets are nonfunctional, and so platelet transfusion
would be required. Although the platelet count of a patient with idiopathic
thrombocytopenia is very close to the “trigger level” for platelet transfusion for an
asymptomatic patient (<10,000), platelet transfusion is not absolutely required, especially
owing to the fact that the platelets in these patients tend to function very well. Platelet
transfusion is contraindicated in patients with thrombotic thrombocytopenic purpura; in
such patients, plasmapheresis with fresh frozen plasma is indicated. In a patient with endstage liver disease that has a platelet count of 50,000, mild bleeding (easy bruising) is not
an indication for platelet transfusion.
4. A 63-year-old multiparous woman is receiving packed red cells to treat
symptomatic anemia after hip replacement surgery. Fifteen minutes into the
transfusion, she has rigors. On physical examination, she appears anxious and
diaphoretic; her temperature is 102.2 F (39 C); the rest of her examination is
normal.
What is the first step in the diagnosis and management of this transfusion reaction?
A.
B.
C.
D.
Administer acetaminophen or meperidine for symptomatic relief
Draw blood for culturing
Stop the transfusion
Send the untransfused blood back to the blood bank for analysis
Concept: To understand the management of febrile transfusion reactions
Answer: C
The most important first step in managing febrile transfusion reactions is to stop the
infusion immediately. Because bacterial infection can be a complication of transfusion or
surgery, drawing blood for culturing is indicated but would not be the first step.
Acetaminophen or, if the rigors are particularly severe, meperidine is helpful in the
management of febrile transfusion reaction but should be preceded by discontinuance of
the infusion. Sending the untransfused blood back to the blood bank is important so that
the blood bank can obtain cultures from the product and verify that there have not been
any errors in its production.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to
Dr. Wendy Gerstein, Department of Medicine, VAMC (111).
1) Topic of module:__________________________
2) On a scale of 1-5, how effective was this module for learning this topic? _________
(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment
below:
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
________________________________________________________________________
4) Was the attending involved in the teaching of this module? Yes/no (please circle).
5) Please provide any further comments/feedback about this module, or the inpatient
curriculum in general:
6) Please circle one:
Attending
Resident (R2/R3)
Intern
Medical student