Acute hemolytic transfusion reaction

Did You Know?

• Rarely, other blood type incompatibilities such as Kidd, Rh, Kell, or Duffy antigen incompatibility can cause AHTR.
• Reactions that begin sooner are typically more severe.

Signs and symptoms

When an acute hemolytic transfusion reaction starts, fever and chills are common. Milder reactions might cause pain in the abdomen, back, flank, or chest. In serious cases, patients can develop low blood pressure, trouble breathing, and dark urine from hemoglobin, which may lead to shock or a bleeding disorder. For someone under anesthesia, blood in the urine is often the first clue. Nausea, vomiting, and wheezing are also possible.

Mechanism

Acute hemolytic transfusion reactions occur when recipient isohemagglutinins (antibodies against A and/or B antigens) destroy donor red blood cells. IgM and, to a lesser extent, IgG antibodies activate the complement cascade; complement C5-C9 forms the membrane attack complex, causing red blood cell lysis. Released free hemoglobin overwhelms binding proteins such as albumin, haptoglobin, and hemopexin, leading to renal vasoconstriction via nitric oxide scavenging, acute tubular necrosis, and acute kidney injury. The antibodies also activate the coagulation cascade through factor XII, potentially causing disseminated intravascular coagulation. Isohemagglutinins activate complement via C3a and C5a, promoting inflammatory cytokine release (IL-1, IL-6, IL-8, TNF-alpha) from white blood cells and activating mast cells to release serotonin and histamine, which increase capillary permeability and vasodilation, producing symptoms such as low blood pressure, fever, chest pain, nausea, vomiting, and wheezing.

Diagnosis

To diagnose an acute hemolytic transfusion reaction, a doctor examines the recipient's blood under a microscope and performs a direct antiglobulin test, which finds IgG antibodies or complement on red blood cells and is usually conclusive. The donor's and recipient's blood are retested for blood type, crossmatch, and antibodies to find the cause. The donor unit is checked for labeling errors or other blood bank mistakes. A gram stain and culture of the donor blood can exclude an infection. Testing urine or plasma for free hemoglobin may also help confirm the diagnosis.

Treatment

Initial treatment for any transfusion reaction, including AHTR, is discontinuation of the transfusion. Fluid replacement and close vital sign monitoring are important. Supportive care may include diuretics, blood pressure support, and treatment of disseminated intravascular coagulation with fresh frozen plasma, cryoprecipitate, and platelet transfusion. Evidence does not support the use of steroids, intravenous immune-globulins, or plasma exchange. Furosemide is the diuretic of choice for decreased urine output; mannitol may also be used. Dopamine is used for blood pressure support as it causes renal vasodilation and increases cardiac output.