Recognition and Management of Suspected Transfusion Reaction

Signs and symptoms of a reaction can be nonspecific, particularly when fever, chills and dyspnea are involved; they can also be due to the underlying disease. Fever, rigors, respiratory distress, hypotension, and tachycardia can occur from reactions caused by hemolysis of incompatible red cells, bacterial contamination of the blood component, or transfusion-related acute lung injury.

Providers and nursing staff must be aware of the signs and symptoms of a transfusion reaction:
  • Temperature rise greater than or equal to 1° C (or 2° F) 
    • Temperature increase must occur during or within four hours of transfusion.
  • Chills, rigors
  • Skin manifestations: urticaria, rash, flushing, pruritis
  • Respiratory symptoms: dyspnea, wheezing, bronchospasm, cyanosis, hypoxia, ventilation difficulty
  • Unexpected fall in blood pressure
  • Unexpected bradycardia or tachycardia
  • Nausea or vomiting
  • Severe headache
  • Red urine
  • Pain in back, chest, or at IV site
  • Oozing/bleeding from multiple sites
  • Angioedema
If the above signs and symptoms develop, be prepared to:

1. Stop the transfusion.

2. Provide appropriate care.

3. Notify the Blood Bank: 

  • East Bank: 612-273-5367
  • West Bank: 612-273-4011

4. Collect blood samples, and

5. Send the blood component bags to the Blood Bank.

Responsibility of Providers to Report Transfusion Reaction

Report all transfusion-related adverse reactions to the Blood Bank promptly.

A transfusion medicine physician will investigate the cause and make recommendations for subsequent transfusions, as appropriate. The information you provide may prevent an adverse reaction in other patients receiving blood components from the same donor.

Transfusion Reaction Categories

  • Allergic reaction
    •  Urticaria
    • Anaphylactic
  • Acute hemolytic transfusion reaction
  • Delayed hemolytic transfusion reaction
  • Hypotensive transfusion reaction
  • Febrile non-hemolytic transfusion reaction
  • Post transfusion purpura
  • Transfusion-associated circulatory overload (TACO)
  • Transfusion-associated dyspnea
  • Transfusion-associated graft versus host disease
  • Transfusion-related acute lung injury (TRALI)
  • Transfusion-transmitted infection

Allergic Reaction

The result of an interaction of an allergen with preformed antibodies. It may present with only mucocutaneous signs and symptoms. An allergic reaction may present in a spectrum ranging from mild urticaria to anaphylaxis.

Signs/Symptoms
The following can occur during or within 4 hours of concluding the transfusion:

  • Maculopapular rash
  • Urticaria (hives)
  • Pruritus (itching)
  • Generalized flushing
  • Localized angioedema
  • Edema of lips, tongue, and uvula
  • Erythema and edema of the periorbital area
  • Conjunctival edema
  • Respiratory distress
  • Bronchospasm
  • Hypotension
Laboratory/Radiology Studies
N/A

Management of an Urticarial Reaction
1. Stop the transfusion.
2. Treat with antihistamines.
3. Notify the Blood Bank:
4. When urticaria and pruritisare the only symptoms and they are successfully treated, the transfusion may be restarted cautiously.
5. If any of the following symptoms accompany the hives, DO NOT restart the transfusion:

  • respiratory distress
  • bronchospasm
  • angioedema
  • periorbital swelling or
  • hypotension
6. Patients should NOT routinely be premedicated with antihistamine unless they have a recurrent history of allergic reactions.

Initial Management of an Anaphylactic Reaction
1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
2. Resuscitate and treat respiratory distress and cardiovascular collapse if present.
3. Notify the Blood Bank.
4. Collect blood samples.
5. Send the blood component bags to the Blood Bank.
6. Order further testing in consultation with the transfusion medicine physician to determine the cause.

Acute Hemolytic Transfusion Reaction (AHTR)

AHTR is the rapid destruction of red blood cells during, immediately after, or within 24 hours after the transfusion. Clinical and laboratory signs of hemolysis are present. No single criterion exists to definitively diagnose this rare disorder. The initial symptoms of a hemolytic transfusion reaction tend to be nonspecific; however, fever is the most common presenting symptom and signs of hemolysis may be subtle.

AHTR usually occurs in the context of ABO incompatibility or other allotypic RBC antigen incompatibility due to patient identification errors.

Signs/Symptoms

Occurs during, immediately after, or within 24 hours of cessation of transfusion with ANY of the following:
  • Fever
  • Chills/rigors
  • Back/flank pain
  • Hypotension
  • Hemoglobinuria occurring during or shortly after cessation
  • of transfusion
  • Epistaxis
  • Oliguria/anuria
  • Renal failure
  • Disseminated intravascular coagulation (DIC)
  • Pain and/or oozing at IV site
Laboratory/Radiology Studies
  • Positive direct antiglobulin test (DAT),
  • Elevated LDH
  • Elevated bilirubin
  • Low haptoglobin
  • Hemoglobinuria
  • Low fibrinogen
  • Elevated plasma hemoglobin
Initial Management of an AHTR
1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
2. Resuscitate and treat respiratory distress and cardiovascular collapse if present.
3. Prevent acute renal failure: ◦Administer large volumes of fluid in order to maintain adequate hydration and urinary output. The rate of fluid administration depends on the severity of hemolysis. The goal of hydration is to obtain a diuresis of at least 100 mL/hour until the urine is negative for hemoglobin.
  • Monitor urine output and color, urinalysis, BUN, creatinine, and electrolytes immediately and at intervals then daily.
  • Maintain adequate blood and perfusion pressure. Use furosemide 80-120 mg IV if urine flow is less than 100 mL/hour.
  • Alkalinize the urine with IV sodium bicarbonate to keep hemoglobin soluble and reduce kidney tubular damage. Alkalization is monitored by urinary pH, which should be maintained greater than 6.5 or 7.
4. If needed, consult a nephrologist.
5. Prevent over-hydration and acute circulatory overload. Monitor fluid status, weight measurements, and signs and symptoms of circulatory overload.
6. Monitor extent of hemolysis by testing for CBC, bilirubin, and haptoglobin.
7. Test and monitor for DIC: INR, aPTT, fibrinogen, d-dimer.
8. Notify the Blood Bank.
9. Collect blood samples.
10. Send the blood component bags to the Blood Bank.
11. Order further testing in consultation with the transfusion medicine physician to determine the cause.

Acute hemolysis can be clinically mild but the fatality rate of a symptomatic severe hemolytic reaction is over 10% and aggressive treatment and close follow-up is important.

Delayed Hemolytic Transfusion Reaction (DHTR)

The recipient develops antibodies to RBC antigen(s) between 24 hours and 28 days after a cross-match compatible transfusion. The RBC transfusion contains an antigen that stimulates a brisk anamnestic response. These antibodies bind to and hemolyze the transfused RBC. The most frequent presentation of DHTR is unexplained anemia or inadequate response to the transfusion (lack of Hgb increase). In rare cases it can present as severe anemia with unexplained fever, jaundice, and renal failure a week or two after a transfusion.

Signs/Symptoms
Patient may be asymptomatic or have symptoms that are similar to but milder than AHTR. Examples of symptoms include:
  • Chills/rigors
  • Fever
  • Jaundice
  • Back/flank pain
  • Hypotension
  • Hemoglobinuria
  • Hematuria
  • Oliguria/anuria
Laboratory/Radiology Studies
  • Positive direct antiglobulin test (DAT) for antibodies developed between 24 hours and 28 days after the transfusion
  • Post-transfusion LDH and bilirubin levels transiently increase and return to baseline in subsequent days
  • Inadequate increase in post-transfusion hemoglobin level or rapid decrease in hemoglobin to pre-transfusion levels
  • Otherwise unexplained appearance of spherocytes

Hypotensive Transfusion Reaction (HTR)

A hypotensive transfusion reaction is a drop in blood pressure occurring during or within one hour post-transfusion. Other symptoms, such as facial flushing, dyspnea, or abdominal cramps may occur but usually hypotension is the sole manifestation.

The reaction occurs less than 15 minutes after starting the transfusion and responds rapidly (within 10 minutes) after stopping the transfusion and beginning supportive treatment.

Signs/Symptoms
Hypotension:
  • Adults (18 years and older): ◦Drop in systolicBP of greater than or equal to 30 mm Hg and
    • SystolicBP less than or equal to 80
  • Infants, children and adolescents (1 year to less than 18 years old): 
    • Greater than 25% drop in systolic BP
  • Neonates and small infants (less than 1 year old or any age and less than 12 kg body weight): 
    • Greater than 25% drop in baseline value using whichever measurement is being recorded (e.g., mean BP)
Laboratory/Radiology Studies N/A

Initial Management of HTR
  1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
  2. Notify the Blood Bank.
  3. Collect blood samples.
  4. Send the blood component bags to the Blood Bank.
  5. Order further testing in consultation with the transfusion medicine physician to determine the cause.

Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

FNHTR often presents as fever and/or chills without hemolysis occurring during or within 4 hours after a transfusion. If transfusion-related, the most common cause is a reaction to passively transfused cytokines or a reaction of recipient antibodies and leukocytes in the blood product.

Signs/Symptoms
  • Occurs during or within 4 hours after the transfusion
  • Fever (greater than or equal to 38 C/100.4 F oral or equivalent and a change of at least 1° C or 2° F from pre-transfusion value)
  • Chills/rigors are present
Note: FNHTR can be present in absence of fever if chills or rigors occur.

Laboratory/Radiology Studies
N/A

Initial Management of FNHTR
  1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
  2. Notify the Blood Bank.
  3. Collect blood samples.
  4. Send the blood component bags to the Blood Bank.
  5. Order further testing in consultation with the transfusion medicine physician to determine the cause.

Post Transfusion Purpura (PTP)

PTP is a severe thrombocytopenia that develops abruptly 5-12 days following the transfusion of cellular blood components and is often accompanied by bleeding. Antibodies in the patient are directed against the Human Platelet Antigen (HPA-1A) system. PTP is most often seen in multiparous women. Due to cross-reactivity or the development of an autoantibody, the transfused platelets and the patient’s own platelets are massively destroyed in this response.

Signs/Symptoms
  • Thrombocytopenia (decrease to less than 20% of pre-transfusion count)

Laboratory/Radiology Studies
  • Alloantibodies in the patient are directed against HPA-1A or other platelet specific antigen detected at or after development of reaction
For transfusion support, please contact the transfusion medicine physician.

Transfusion-Associated Circulatory Overload (TACO)

TACO occurs when an infusion volume cannot be effectively processed by the recipient either due to a high rate and/or volume of infusion or an underlying cardiac or pulmonary pathology.

Signs/Symptoms

New onset or exacerbation of three or more of the following within six hours after a transfusion:

  • Acute respiratory distress (dyspnea, orthopnea, cough)
  • Evidence of positive fluid balance
  • Elevated brain natriuretic peptide (BNP)
  • Radiographic evidence of pulmonary edema
  • Evidence of left heart failure
  • Elevated central venous pressure (CVP) 
Laboratory/Radiology Studies N/A

Approximate volumes of Blood Components
Red Blood Cells 300 mL
Apheresis Platelets 250-400 mL
Plasma 250 mL
Pooled Cryoprecipitate 100 mL

Initial Management of TACO
  1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
  2. Notify the Blood Bank.
  3. Collect blood samples.
  4. Send the blood component bags to the Blood Bank.
  5. Order further testing in consultation with the transfusion medicine physician to determine the cause.
  6. Treat according to patient’s underlying cause for fluid overload.

Transfusion-Associated Dyspnea (TAD)

TAD is characterized by respiratory distress within 24 hours of stopping a transfusion that does not meet the criteria of TRALI, TACO, or allergic reaction. It is not TAD if the respiratory distress can be explained by a patient’s underlying or pre-existing medical condition.

Signs/Symptoms
  • Acute respiratory distress that occurs within 24 hours of stopping a transfusion
Laboratory/Radiology Studies
N/A

Transfusion-Associated Graft versus Host Disease (TA-GVHD)

TA-GVHD is the introduction of immunocompetent lymphocytes into susceptible hosts. The allogeneic lymphocytes engraft, proliferate, and destroy host cells. If performed, a marrow study shows hypoplasia, aplastic anemia, or marked hypocellularity with a lymphohistiocytic infiltrate. It occurs from two days to six weeks after the conclusion of a transfusion.

TA-GVHD can be prevented by irradiation of RBCs and platelets. This affects nucleated cells only, and prevents lymphocyte proliferation without affecting their viability. TA-GVHD cannot be prevented by washing or leukoreduction.

Signs/Symptoms
  • Fever
  • Characteristic rash: erythematous, maculopapular eruption centrally that spreads to extremities and may, in severe cases, progress to generalized erythroderma and hemorrhagic bullous formation
  • Hepatomegaly
  • Diarrhea
Laboratory/Radiology Studies
  • Liver dysfunction (i.e., elevated ALT, AST, Alkaline phosphatase, and elevated bilirubin)
  • Pancytopenia
  • Characteristic histological appearance of skin biopsy or liver biopsy

Transfusion-Related Acute Lung Injury (TRALI)

TRALI is acute hypoxemia with a chest x-ray showing bilateral infiltrates in the absence of left atrial hypertension (e.g., circulatory overload). TRALI onset can be abrupt (during/within six hours of transfusion). It most frequently results from a platelet transfusion. The cause is usually related to the passive transfer of HLA or neutrophil antibodies.

Signs/Symptoms
  • NO evidence of acute lung injury (ALI)* prior to transfusion
  • ALI onset during or within 6 hours of cessation of transfusion
    • Hypoxemia defined by any of these methods: ◦PaO2 / FiO2 less than or equal to 300 mm Hg
    • Oxygen saturation less than 90% on room air
  • No evidence of left atrial hypertension (e.g., circulatory overload)
  • New bilateral infiltrates on chest radiograph
  • Variable: fever, chills, hypotension

*If there is a preexisting acute lung injury, a diagnosis of “possible TRALI” may be made.

Laboratory/Radiology Studies
N/A

Initial Management of TRALI
  1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
  2. Administer oxygen and treat respiratory failure as necessary.
  3. Avoid diuretic administration (TACO usually responds to diuretics, but TRALI does not).
  4. Notify the Blood Bank.
  5. Collect blood samples.
  6. Send the blood component bags to the Blood Bank.
  7. Order further testing in consultation with the transfusion medicine physician to determine the cause.
  8. No specific therapy is available for TRALI.
Treatment of TRALI is supportive. Supportive therapy results in an 80-90% survival rate.

Transfusion-Transmitted Infection (TTI)

A TTI is caused most commonly by bacteria, but it can also be caused by a virus, parasite, or other potential pathogen transmitted in donated blood to the transfusion recipient. Bacterial contamination of blood components occurs infrequently but when it occurs it usually involves platelets or red cells. The initial symptoms from receiving a bacterially-contaminated blood component may be nonspecific (e.g., fever, chills, back pain, hypotension, dyspnea, etc.).

Pathogens of well-documented importance in blood safety
Bacterial Viral Parasitic Other
  • Escherichia coli
  • Klebsiella oxytoca
  • Klebsiella pneumoniae
  • Pseudomonas aeruginosa
  • Serratia marcescens
  • Staphylococcus aureus
  • Staphylococcus epidermidis
  • Staphylococcus lugdunensis
  • Syphilis (Treponema pallidum)
  • Yersinia enterocolitica
  • Cytomegalovirus (CMV)
  • Enterovirus
  • Epstein Barr (EBV)
  • Hepatitis B
  • Hepatitis C
  • HIV-1
  • HIV-2
  • Parvovirus B-19
  • HTLV-1
  • HTLV-2
  • West Nile Virus
  • Babesiosis 
  • Chagas disease (Trypanosoma cruzi)
  • Malaria (Plasmodium spp.)
  • Creutzfeldt-Jakob Disease, Variant (vCJD)

Initial Management of Bacterially-Contaminated Blood Transfusion
  1. Stop the transfusion. DO NOT RESTART THE TRANSFUSION.
  2. Notify the Blood Bank.
  3. Blood cultures should be collected for a suspected septic transfusion reaction before antibiotics are started.
  4. Send the blood component bags to the Blood Bank.
  5. Order further testing in consultation with the transfusion medicine physician to determine the cause.

Other Transfusion Complications

Patients receiving massive transfusions are at risk for hypothermia (from cold blood), hypocalcemia (from the citrate anticoagulant in blood that binds calcium), metabolic alkalosis (from citrate being metabolized to bicarbonate by the liver), hyperkalemia (particularly in patients with renal dysfunction), acidosis, or dilutional coagulopathy.

Patients with chronic anemia (aplastic anemia, hemoglobinopathies, etc.) receiving multiple RBC transfusions over time, can develop hemosiderosis (iron overload) because each RBC transfusion contains 250 mg of iron. Humans do not have an efficient mechanism for excreting excess iron.

Reporting Transfusion-Related Fatality

If a transfusion is suspected to have caused a death, this must be reported to the Blood Bank. If verified, the Blood Bank must report this to the FDA and to the blood supplier within 24 hours.