Blood Transfusion Reactions

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Introduction

Many individuals require blood components and blood products. As per the BC Transfusion Medicine Advisory Group (BCTMAG), a blood component is “at therapeutic component of blood intended for transfusion,” and includes red cell, platelets, plasma, cryoprecipitate, and granulocytes. The BCTMAG describes blood products as “any therapeutic product, derived from human blood or plasma, and produced by a manufacturing process,” including human serum albumin, immunoglobulin preparations, and recombinant or porcine coagulation factors. Receiving any of these products may result in a transfusion reaction.

Definitions

In accordance with national consensus guidelines, a transfusion reaction is defined as “an undesirable and unintended occurrence during or after the administration of any blood component/product, that could be considered to be related to the said product.”

Although blood transfusions are generally safe, adverse reactions may occur for a number of different reasons. Most of the time, the reaction is mild and non-life threatening, but serious reactions do occur and require immediate treatment.

Blood transfusion reactions can be classified based on the timing of onset (acute vs. delayed) and the pathophysiological mechanism (immune vs. non-immune related). Acute reactions occur within 24hours of the start of the transfusion, whereas delayed reactions occur more than 24hours after the start of infusion. Immune reactions typically involve antibody reactions between the donor and recipient’s cells. Non-immune reactions may be caused by the properties of the different components within the stored blood.

In addition, blood transfusion reactions may be caused by introduction of infectious organisms and secondary sepsis.

The following is a table summarizing the most common blood transfusion reactions:

Table 1. Common blood transfusion reactions

Acute

Delayed

Immune

ABO incompatibilityAllergic reactionAnaphylaxis

Acute Hemolytic Transfusion Reaction

Febrile Non-Hemolytic Transfusion Reaction

Transfusion-Related Acute Lung Injury

Delayed Hemolytic TransfusionDelayed Serologic Transfusion ReactionAllo-Immunization

Transfusion-associated Graft versus Host Disease

Post-transfusion Purpura

Non-immune

Transfusion-Associated Circulatory OverloadHypotensive Transfusion ReactionMetabolic imbalance

Infectious (bacterial)

Infectious (HBV, HCV, HIV, EBV, CMV, syphilis, malaria, West Nile virus, lyme disease, prion diseases)Iron overloadIVIg asceptic meningitis

The most common causes of transfusion-related deaths across all age groups in Canada are transfusion related acute lung injury, transfusion associated circulatory overload, acute haemolytic transfusion reaction secondary to ABO incompatibility, and transfusion associated sepsis.

Pathogenesis and Clinical Presentation

The clinical presentation of the different types of blood transfusion reactions varies depending on the pathogenic mechanism. Although the same reactions can occur in both pediatric and adult populations, the frequency of occurrence varies for some conditions. Note that different transfusion reactions may present with similar signs and symptoms, and therefore be difficult to differentiate.

The following is a table summarizing the pathogenesis and clinical presentation of the most common transfusion reactions:

Table 2: Pathogenesis and Clinical presentation of common blood transfusion reactions

Transfusion reaction	Pathogenesis	Clinical presentation
Transfusion related Acute lung injury	Leukocyte antibodies in the donor blood attack host Associated with higher concentrations of plasma, e.g.: fresh frozen plasma	Within 2 to 6hrs of start of transfusion Shortness of breath, work of breathing Coughing Tacchypnea, hypoxemia Tachycardia Hypotension Fever Bilateral pulmonary infiltrates
Transfusion associated circulatory overload	Rapid or excess volume delivery in a susceptible patient (e.g.: neonate, cardiac abnormality, delicate hemo-dynamic status, renal failure)	Within 6hours of end of transfusion Shortness of breath, chest tightness Cough Headache Tacchypnea Tachycardia Hypotension Signs of volume overload: jugular venous distension, cardiac S₃, Pulmonary edema
Acute haemolytic transfusion reaction	ABO incompatibility Other RBC antigen incompatibilities (eg. Rh, Duffy, Kell)	Fever Chills, rigors Apprehensiveness Pain in lower back, flanks, chest, along infusion vein Hypotension Bleeding Hemoglobinuria Renal failure
Sepsis	Bacterial contamination in blood product enter recipient Result in bacteremia and immune reaction.	Fever, chills, sweats Warm or clammy skin Vomiting Rash Tachycardia, tachypnea Hypothermia
Delayed haemolytic transfusion reaction	Allo-immunization to other antigens.	Fever, chills Jaundice Malaise Back pain Unexpected anemia, usually within first two weeks after transfusion
Febrile non-hemolytic transfusion reaction	Humoral and cellular-mediated inflammatory reaction Second most common type of blood transfusion reaction in pediatric population	Onset 1-2 hours after transfusion Fever Chills, rigors, malaise Headache Nausea/ vomiting Increase in diastolic BP
Allergic transfusion reaction	Inflammatory reaction resulting in release of histamine by mast cells Most common type of blood transfusion reaction in pediatric population	Urticarial rash Pruritus Nausea, vomiting Diarrhea, abdominal cramps Anxiety Hypotension (less common) Dyspnea (less common)
Anaphylactic transfusion reaction	Severe allergic reaction against transfused blood	Immediate respiratory distress (seconds to minutes) Upper airway edema→obstruction Lower airway signs and symptoms (bronchospasm, wheezing, retractions, SOB) Loss of consciousness Vomiting Hypotension, weak pulses, with ultimately circulatory collapse

Assessment

The cornerstone to the approach of most problems in medicine includes a thorough history and physical exam. This is then followed by ancillary investigations as required.

Important aspects to include in the history of a patient suspected of developing a transfusion reaction include:

Confirm that the patient had recently received a blood transfusion
Constitutional symptoms, including fever, chills, sweats, decreased appetite
Elicit symptoms of difficulty breathing, such as dyspnea or wheezing
Gastrointestinal symptoms, including abdominal cramps, diarrhea, nausea, vomiting
Headache, dizziness
Past medical history: previous transfusions and whether there were any reactions

Perform a comprehensive physical exam, with particular attention to:

Vital signs: presence of hypotension, hypertension, tachycardia, tachypnea, fever >38°C and a rise of >1°C since the onset of transfusion, sudden onset hypoxemia <90%
Patient affect: anxiety, apprehension
Erythema or tenderness at IV site
Cutaneous changes: erythema, urticaria, pallor, jaundice
Appearance of urine: red or brown urine may indicate hemolysis and hemoglobinuria

Investigations

ABO blood typing and cross matching: to assess donor-recipient ABO and Rh compatibility
Direct antiglobulin test (direct Coombs test): to identify immune-mediated hemolysis
Complete blood count (CBC): to assess extent of anemia, rule out DIC
Serum haptoglobin: low values suggest intravascular hemolysis
Urinalysis: look for hemoglobinuria
Serum creatinine and blood urea nitrogen (BUN): monitor renal function
Serum LDH: elevated values can be due to hemolysis

Management

Whenever a transfusion reaction is suspected, it is crucial to stop the transfusion and send the blood product with its tubing to the blood bank for further testing. As with all potentially fatal reactions, initial management is aimed at establishing and maintaining a patient’s ABCs. Next, reconfirm that the patient is receiving the correct product, unit/lot, and that it is destined for this specific patient. Notify the blood bank of any suspicions or errors. Finally, investigation as appropriate, including blood cultures, chest radiographs. Ensure that a member of the health care team informs the patient of what is going on.

References

Hillyer CD, Strauss RG, and Luban NLC. Handbook of Pediatric Transfusion Medicine. Elsevier Academic Press, 2004, San Diego.
Dzieczkowski Jeffery S, Anderson Kenneth C, “Chapter 107. Transfusion Biology and Therapy” (Chapter). Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL, Jameson JL, Loscalzo J: Harrison’s Principles of Internal Medicine, 17e:
http://www.accessmedicine.com/content.aspx?aID=2866013.
Aqui N, Kuter DJ, Logdberg L, Sisson SD. Blood transfusion reactions [Online]. July 2010. Available from: First Consult, MD Consult [cited 16 January 2011]
BC Provincial Blood Coordinating Office. Transfusion reaction education [online]. December 2011. www.pbco.ca/index.php?option=com_content&task=category&sectionid=9&id=67&Itemid=49

Acknowledgements

Writer: Donald Yung

Resident Editor: Katryn Paquette