Attending Version
Blood transfusion reactions module; created by Dr. Farzana Harji
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 globmerulus 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

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:
You are called to admit a patient with GIB in the ER and gather the following information:
HPI: 56 yom with long history of alcoholism and multiple past admissions for alcohol withdrawal presents to
the ER complaining of nausea, vomiting and shakiness. Patient states that he has been drinking 12 to 24 pack of
beer each day for the past week and started getting sick yesterday when vomiting started. Upon further
questioning, he reveals that he has been vomiting blood since this morning and started feeling quite dizzy. He
also describes his stool as being black for the past week. He also admits to having one previous similar episode
about 6 months ago and was admitted at another hospital. He recalls having an upper scope, and that he had to
be banded at areas where he was bleeding.
You glance at the vitals while you are talking with the patient and observe the following:
Temp 37.6, rr 18,
hr 120,
b/p 90/60,
O2 sat 93% RA
You also noted the lab results prior to the interview:
WC 10,
h/h 8/24,
plts 100
Chem. Na 143, K 2.9, Cl 103, Co2 25, BUN/Cr 30/0.9, glc 103
LFT: TP 7.8, alb 3.0, ast/alt 248/100, alk phos 72, TB 1.5, indirect 0.9, direct 0.6
You note the ER Course next: patient is receiving 1 liter bolus of normal saline and blood transfusion is started.
Patient has refused NG lavage, but did vomit 100cc of red blood while in the ER. While you are evaluating this
patient for admission, the tech comes by to take the temperature and notes a fever of 38.7 and patient complains
of dyspnea. What is your next step in management?
Answer: Stop the transfusion since you are not sure if this represents a benign or serious blood transfusion
reaction. Send the red cell bag back to blood bank for repeat typing and cross-matching, determine if there has
been a clerical error and continue with fluid boluses in the meantime. Continue assessing patient to determining
that a hemolytic reaction is not 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 continued aggressively to maintain good urine output and adequate blood pressure. Get frequent
vital signs and keep a close eye on this patient. In this case, it’s also prudent to consider other diagnoses that
may look similar such as sepsis or ARDS. In addition, you are not sure if this patient his having active variceal
bleeding and the urgent need for NG lavage needs to be re-addressed with the patient.
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 end-stage 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.