4.4 Transfusion Reactions & Adverse Effects

Transfusion Reactions: Immediate Response and Investigation

A transfusion reaction is any adverse event occurring during or after the administration of blood components. The immediate clinical response to ANY suspected reaction must be: Stop the transfusion immediately, keep the IV line open with normal saline, and notify the physician and blood bank.

The immediate laboratory investigation involves three critical steps:

1. Clerical Check: Meticulously verify patient identification and blood unit labeling to rule out a major mismatch.
2. Visual Inspection: Examine the post-transfusion plasma or serum for visible free hemoglobin (pink/red color indicating hemolysis) and compare it to the pre-transfusion sample.
3. Direct Antiglobulin Test (DAT): Perform a DAT on the post-reaction sample to check for in vivo sensitization of the donor cells.

Acute Hemolytic Transfusion Reactions (AHTR)

AHTRs occur rapidly, often within minutes of initiating a transfusion, sometimes after only a few milliliters of blood have infused. They are most commonly caused by ABO incompatibility (e.g., group A blood given to a group O patient) resulting from catastrophic clerical, identification, or phlebotomy errors. The recipient's pre-formed, potent IgM antibodies rapidly bind to the transfused red cells, activating the full complement cascade all the way to the membrane attack complex (MAC), leading to explosive intravascular hemolysis.

• Symptoms: Fever, chills, severe back/flank pain (indicative of acute kidney injury), hypotension, hemoglobinemia (red plasma), hemoglobinuria (red urine), oozing from the IV site, and feelings of impending doom. Severe cases rapidly progress to Disseminated Intravascular Coagulation (DIC), renal failure, shock, and death.
• Laboratory Findings: Positive DAT (though may be negative if all transfused cells were destroyed instantly), visible hemolysis in plasma, precipitously decreased haptoglobin, elevated LDH and indirect bilirubin, hemoglobin in urine.

Delayed Hemolytic Transfusion Reactions (DHTR)

DHTRs typically manifest 3 to 14 days after a transfusion. They are usually caused by an anamnestic (secondary memory) immune response. A patient who was previously immunized (e.g., by pregnancy or past transfusion) has an antibody titer that has dropped over months or years below the detectable limit of standard laboratory antibody screens. The blood is issued as compatible. However, when re-exposed to the antigen via the transfusion, the immune system rapidly mounts a massive IgG antibody production. These IgG antibodies coat the transfused cells, leading to extravascular hemolysis (removal and destruction of the sensitized red cells by macrophages in the spleen and liver).

• Common Culprits: Antibodies in the Kidd (Jka, Jkb) system are the classic and notorious cause of DHTRs due to their tendency to fade rapidly from circulation.
• Symptoms: Often mild or entirely asymptomatic. The patient presents with an unexplained drop in hemoglobin/hematocrit days after the transfusion, mild jaundice, and a low-grade fever.
• Laboratory Findings: Positive DAT (typically showing a mixed-field reaction, as only the donor cells are coated), a newly positive antibody screen identifying the culprit antibody, and elevated indirect bilirubin.

Non-Hemolytic Transfusion Reactions

Febrile Non-Hemolytic Transfusion Reaction (FNHTR)

The most frequent type of reaction overall. Defined as a temperature rise of ≥1°C occurring during or shortly after transfusion, with no other identifiable cause (like hemolysis or bacterial contamination).

• Cause: Antibodies in the recipient reacting to human leukocyte antigens (HLA) or leukocyte fragments present on the small amount of transfused donor white blood cells. Alternatively, it can be caused by inflammatory cytokines (like IL-1 or TNF) that accumulated in the blood component bag during storage.
• Prevention: Universal leukoreduction of blood components (filtering out >99.9% of WBCs before storage) has drastically reduced the incidence of FNHTRs.

Allergic and Anaphylactic Reactions

• Mild Allergic (Urticarial): The recipient possesses antibodies that react against soluble donor plasma proteins. Symptoms are limited to hives (urticaria), rash, and itching. Crucially, this is the only reaction where the transfusion might be restarted (after physician evaluation and administration of antihistamines like diphenhydramine).
• Severe Anaphylactic: A rapid onset, life-threatening systemic allergic reaction. It classically occurs in patients who have a severe IgA-deficiency and have formed potent anti-IgA antibodies from prior environmental exposure or pregnancy. When exposed to normal donor plasma containing IgA, profound respiratory distress, bronchospasm, and hypotensive shock occur. Prevention requires washing red cells extensively to remove all plasma or utilizing blood products exclusively from other known IgA-deficient donors.

TRALI vs. TACO: The Pulmonary Complications

These two entities represent the leading causes of transfusion-related mortality and must be clinically differentiated.

• Transfusion-Related Acute Lung Injury (TRALI): An immune-mediated complication. Donor plasma contains anti-HLA or anti-HNA (human neutrophil antigen) antibodies (often from multiparous female donors who were immunized during pregnancy). These antibodies react with the recipient's white blood cells in the pulmonary microvasculature, triggering neutrophil activation, massive capillary leakage, and acute non-cardiogenic pulmonary edema. It presents with acute respiratory distress and severe hypoxemia, typically accompanied by hypotension and fever.
• Transfusion-Associated Circulatory Overload (TACO): An iatrogenic, non-immune volume overload. Caused by transfusing blood too rapidly or in too large a volume for the patient's cardiovascular system to handle, leading to congestive hydrostatic heart failure. High risk in the elderly, infants, and patients with pre-existing cardiac issues. It presents with dyspnea, orthopnea, severe hypertension, tachycardia, and a markedly elevated Brain Natriuretic Peptide (BNP).

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

A rare but almost universally fatal complication (mortality >90%). It occurs when immunocompetent donor T lymphocytes are transfused into a profoundly immunocompromised recipient (e.g., bone marrow transplant patients, neonates). Because the recipient's immune system cannot destroy the foreign cells, the donor T cells engraft, proliferate, and mount a massive immune attack against the recipient's tissues (skin, liver, GI tract, bone marrow).

• Prevention: The only effective prevention is gamma irradiation of cellular blood components prior to transfusion, which cross-links the donor T-cell DNA and renders them incapable of replicating.

Iron Overload (Hemosiderosis)

A long-term complication seen in patients requiring chronic, life-long transfusion therapy (e.g., Thalassemia major, Sickle Cell Disease). Because the human body has no physiological mechanism to excrete excess iron, the iron from hundreds of transfused RBC units accumulates in the liver, heart, and endocrine organs, leading to organ failure. Treatment requires the daily administration of iron-chelating drugs (like deferoxamine).