Transfusion reactions can be acute or delayed. Acute reactions occur during or within 24 hours of transfusion and commonly include fever, chills, itching, or hives, which usually resolve without treatment. Severe signs such as sudden shortness of breath, red urine, high fever, or loss of consciousness may indicate a life-threatening reaction. 

Red urine during transfusion may be hematuria or hemoglobinuria. Centrifuging urine with hematuria causes red blood cells to settle, leaving a clear supernatant, while hemoglobinuria remains uniformly red. 

Delayed hemolytic transfusion reactions (DHTRs) occur in patients with prior transfusions when low-level antibodies become boosted after exposure to antigen-positive RBCs, leading to hemolysis several days later. DHTRs are rare, about 1 in 5,400 transfusions, but can be severe in sickle-cell disease, where both donor and patient RBCs may be destroyed, sometimes progressing to hyperhemolysis syndrome with impaired reticulocyte response. 

The frequency of transfusion reactions varies, with mild allergic reactions and febrile non-hemolytic reactions being relatively common, while anaphylaxis, acute hemolytic reactions, and septic events are rare. Among fatal outcomes, transfusion-related acute lung injury (TRALI) is reported most frequently, whereas delayed or long-term adverse effects are usually linked to transmission of infectious diseases. 

Both the incidence and severity of transfusion reactions depend on the reaction type, the prevalence of infections in the donor population, and the level of patient monitoring after transfusion. Advances in donor screening, improved laboratory testing, and the use of automated data systems have contributed to a steady decline in transfusion-related risks and mortality. 

Acute Reactions 

Mild allergic: Caused by hypersensitivity to proteins in the donor blood. 

Anaphylactic: A severe allergic reaction, sometimes seen in patients with IgA deficiency who develop antibodies against IgA and receive IgA-containing products. 

Febrile non-hemolytic: Usually results from cytokines released by donor white blood cells. 

Septic: Triggered by bacterial contamination or endotoxins in the transfused product. 

Acute hemolytic: Can be immune-mediated, due to recipient antibodies against donor antigens, or non-immune, caused by pretransfusion RBC damage such as heat or osmotic stress. 

Transfusion-associated circulatory overload (TACO): Occurs when transfused volume exceeds the patient’s circulatory capacity, leading to hypervolemia. 

Transfusion-related acute lung injury (TRALI): Antibodies in donor blood react with recipient antigens, activating the immune system and causing pulmonary edema. Risk factors include infection, recent surgery, or inflammation. 

Delayed Reactions 

Delayed hemolytic: Results from an anamnestic immune response to antigens the patient was previously exposed to through transfusion or pregnancy. 

Transfusion-associated graft-versus-host disease (TA-GVHD): Occurs when donor lymphocytes engraft in an immunocompromised recipient, attacking host tissues. This reaction is rare but often fatal. 

Immune-mediated transfusion reactions usually arise from incompatibility between the transfused blood product and the recipient. They can result from naturally occurring antibodies in the recipient, such as anti-A and anti-B, which are commonly responsible for acute hemolytic transfusion reactions, or from antibodies produced in response to foreign antigens, known as alloantibodies. Alloantibodies contribute to a variety of reactions, including mild allergic reactions, febrile non-hemolytic reactions, acute hemolytic reactions, and anaphylaxis. Reactions can also occur due to antibodies present in the donor blood, which are implicated in conditions such as transfusion-related acute lung injury (TRALI). 

Non-immune transfusion reactions are generally caused by the physical properties of blood components or by transmission of infectious agents. For example, bacterial contamination can lead to septic transfusion reactions, often resulting from inadequate disinfection of the donor’s arm, bacteremia in the donor at the time of collection, or improper handling of the blood product after collection. 

Transfusion reactions may also occur due to factors unrelated to the blood itself. Notable examples include transfusion-associated circulatory overload (TACO) and hypothermia. 

Type of Reaction: Antibody-mediated hemolysis, TRALI, and anaphylaxis carry higher morbidity and mortality, while non-immune hemolysis, mild allergic, and febrile reactions are usually self-limiting. 

Volume and Rate: Large volumes of incompatible blood increase severity; rapid transfusion can worsen TACO. 

Patient Factors: Comorbidities (renal, cardiac, or pulmonary disease), immune status, and IgA deficiency influence risk and outcomes. 

Donor Factors: Antibodies in donor blood (HLA/HNA) and RBC damage or contamination increase reaction severity. 

Recognition and Management: Early detection, stopping transfusion, and supportive interventions, including ventilation for TRALI, improve prognosis. 

Age group  

All age groups can experience transfusion reactions, but the elderly and very young children may be at higher risk for severe outcomes due to reduced physiological reserve. 

Before initiating a transfusion, a comprehensive review of the patient’s medical history and current health status is essential. Vital signs are typically monitored and recorded every 15 minutes. Signs that may suggest a reaction include hives, itching, fever exceeding 1°C above baseline, chills, hypotension, and difficulty breathing. 

Comorbidities: Cardiovascular disease, renal insufficiency, lung disease, or immunocompromised states increase the risk and severity of reactions. 

Activity: Patients who are critically ill, post-surgical, or undergoing intensive therapies may have heightened susceptibility to complications such as TACO, TRALI, or severe hemolysis. 

Acute reactions: Typically occur during or within 24 hours of transfusion, ranging from mild allergic or febrile symptoms to severe hemolysis, anaphylaxis, or TRALI. 

Delayed reactions: May appear days to weeks later, often presenting as delayed hemolytic reactions or transfusion-associated graft-versus-host disease. 

If a transfusion reaction is suspected, the transfusion should be stopped immediately, and the intravenous line maintained with an appropriate fluid, usually 0.9% saline. A clerical check of the blood product and patient identification should be performed. The patient’s vital signs should be closely monitored and recorded every 15 minutes. A post-transfusion blood sample should be collected and sent to the laboratory, along with the blood bag and tubing if available. The blood bank typically conducts further testing and clerical verification to exclude an incompatible transfusion. 

Hematology

This refers to altering external or internal factors to reduce triggers or risks associated with a condition or treatment. In transfusion or medical management, it may include: 

Controlling temperature to prevent hypothermia during transfusion. 

Reducing exposure to allergens to minimize allergic reactions. 

Optimizing patient positioning and mobility to prevent circulatory overload or respiratory complications. 

Ensuring a calm and monitored setting for early detection of adverse reactions. 

Hematology

Diphenhydramine (Benadryl, Alka-Seltzer Plus Allergy, Benadryl Allergy Dye-Free LiquiGels) 
This first-generation antihistamine has both antihistaminic and anticholinergic properties. It works by blocking histamine at receptor sites on target cells. It is commonly prescribed for relief of urticaria, itching, and other allergic manifestations, including those associated with blood product reactions. 

Cimetidine (Tagamet HB) 
An H2 receptor antagonist that can be used in combination with H1 antihistamines to enhance symptom control. This dual approach may help manage itching, flushing, urticaria, pruritus, or contact dermatitis that does not adequately respond to H1 blockade alone. It should be administered as an adjunct, not a substitute, to H1 antihistamines. 

Epinephrine (Adrenalin, Auvi-Q, EpiPen)
A sympathomimetic drug that stimulates both α- and β-adrenergic receptors. Its effects include relaxation of bronchial smooth muscle, increased cardiac output, and enhanced vascular tone. 

Dopamine (Intropin)
A direct precursor of norepinephrine and epinephrine, dopamine exerts dose-dependent effects by activating dopaminergic, β-adrenergic, and α-adrenergic receptors, leading to improved cardiac contractility and vascular support. 

Genomic Medicine

Geriatrics

Hematology

Immediate Response 

At the first sign of a transfusion reaction, the transfusion should be stopped immediately. Intravenous access should be maintained using 0.9% saline, and the patient’s vital signs assessed and stabilized. The treating physician and blood bank must be notified without delay. 

Assessment and Investigation 

A clerical check of the patient’s identification and the blood product should be performed. Post-transfusion blood samples should be collected, and the blood bag and tubing retained for laboratory evaluation. The type and severity of the reaction should be determined to guide further management. 

Supportive Treatment 

Treatment is primarily supportive and may include antihistamines for allergic reactions, antipyretics for febrile reactions, or oxygen and intravenous fluids for more severe reactions. Any complications, such as hypotension, renal failure, or respiratory distress, should be promptly managed. 

Follow-Up and Documentation 

Patients should be monitored until symptoms resolve, with vital signs and clinical findings documented. The reaction must be reported to the blood bank and relevant regulatory authorities, and measures should be implemented to prevent recurrence in future transfusions.