An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milliliters of blood. The reaction is triggered by host antibodies destroying donor red blood cells. AHTR typically occurs when there is an ABO blood group incompatibility, and is most severe when type A donor blood is given to a type O recipient. Signs and symptoms Early acute hemolytic transfusion reactions are typically characterized by fever, which may be accompanied by rigors (chills). Mild cases are also typically characterized by abdominal, back, flank, or chest pain. More severe cases may be characterized by shortness of breath, low blood pressure, hemoglobinuria, and may progress to shock and disseminated intravascular coagulation. In anesthetized or unconscious patients, hematuria (blood in the urine) may be the first sign of AHTR. Other symptoms include nausea, vomiting, and wheezing. Causes The most common cause of acute hemolytic transfusion reaction is ABO incompatibility, which is typically due to human error that results in a recipient receiving the incorrect blood product. Rarely, other blood type incompatibilities can cause AHTR, the most common of which is Kidd antigen incompatibility. Rh, Kell, and Duffy antigen incompatibility have also been implicated in AHTR. Mechanism Antibodies against A and B blood groups (isohemagglutinins) present in the recipient's blood destroy the donor red blood cells. They also activate the coagulation cascade (blood clotting system) via factor XII, which can lead to disseminated intravascular coagulation and kidney damage. Isohemagglutinins also activate the complement cascade via C3a and C5a, which then promote inflammatory cytokine release from white blood cells. These inflammatory cytokines include IL-1, IL-6, IL-8, and TNF-alpha, which cause symptoms of low blood pressure, fever, chest pain, nausea, vomiting, and wheezing. Diagnosis The diagnosis of AHTR is made with microscopic examination of the recipient's blood and a direct antiglobulin test. The donor and recipient blood can be re-tested with a type, crossmatch, and antibody screen to determine the cause of the reaction. Treatment Initial treatment for any type of transfusion reaction, including AHTR, is discontinuation of the transfusion. Fluid replacement and close monitoring of vital signs are important. People with AHTR are managed with supportive care, which may include diuretics, blood pressure support, and treatment of disseminated intravascular coagulation (with fresh frozen plasma, cryoprecipitate, and platelet transfusion). Furosemide is