What acute hemolytic transfusion reaction occurs if a patient receives ABO‑incompatible and Rh‑incompatible blood?

Acute Hemolytic Transfusion Reaction from ABO and Rh Incompatibility

If a patient receives both ABO-incompatible and Rh-incompatible blood, an acute hemolytic transfusion reaction (AHTR) will occur within minutes to 24 hours, characterized by intravascular red cell destruction, hemoglobinuria, disseminated intravascular coagulation, acute renal failure, shock, and potentially death. 1, 2

Pathophysiology of the Reaction

The immune conflict between donor red blood cell antigens and recipient antibodies triggers a cascade of life-threatening events:

• Complete complement activation occurs when ABO antibodies (naturally occurring IgM) bind to incompatible donor red cells, causing immediate intravascular hemolysis 2
• Complement cleavage products (C3a, C5a) mediate the acute clinical symptoms including pain, restlessness, nausea, skin flushing, dyspnea, and shock 1
• Systemic inflammatory response syndrome develops from massive cytokine release 2
• Activation of the kinin system, intrinsic clotting cascade, and fibrinolysis leads to hypotension, disseminated intravascular coagulation (DIC), diffuse bleeding, and disruption of microcirculation 2
• Renal failure results from hemoglobinemia, hemoglobinuria, and microcirculatory disruption 1, 2

The Rh incompatibility adds additional immune-mediated hemolysis, though typically less severe than ABO incompatibility unless the patient has been previously sensitized. 3

Clinical Presentation Timeline

Immediate Symptoms (Within Minutes)

• Tachycardia and hypotension as the first signs 4
• Fever from cytokine release 4, 1
• Pain (back pain, chest pain, abdominal pain) 1
• Restlessness and anxiety 1
• Skin flushing 1
• Dyspnea 1
• Nausea 1

Progressive Symptoms (Hours)

• Hemoglobinuria (red or brown urine) from intravascular hemolysis 4, 1, 5
• Jaundice from bilirubin accumulation 1
• Severe anemia despite transfusion 1
• Disseminated intravascular coagulation with diffuse bleeding 2
• Acute renal failure progressing to anuria 5
• Shock from vasomotor collapse 1, 2

Critical Severity Factors

ABO incompatibility is absolutely the most dangerous transfusion error and causes immediate, severe intravascular hemolysis with high mortality risk. 4, 6 The severity increases with:

• Large volume of incompatible blood transfused 6
• Geriatric patients 6
• Patients with cardiac and renal comorbidities 6
• Negative direct antiglobulin test (DAT) indicating complete hemolysis 6
• Red plasma color and macroscopic hemoglobinuria indicating massive intravascular destruction 6

Immediate Management Protocol

First Actions (Within Seconds)

• Stop the transfusion immediately at the first sign of reaction 4
• Maintain IV access with normal saline 4
• Contact the transfusion laboratory immediately and return the blood product for investigation 4
• Double-check all documentation to identify the administration error 4

Monitoring Requirements

• Continuous vital signs every 15 minutes: heart rate, blood pressure, temperature, respiratory rate 4
• Watch for hemoglobinuria (visual inspection of urine) 4
• Monitor for signs of DIC: diffuse bleeding, petechiae 2

Pharmacologic Interventions

• Antihistamines for allergic symptoms 4
• Steroids (methylprednisolone or prednisone 1-4 mg/kg/day) for severe reactions 4
• Intramuscular or intravenous epinephrine if anaphylactic 4

Advanced Interventions for Severe Cases

Plasma exchange (PE) should be considered early in the course, not as a last resort, particularly when: 6

• Patient has cardiac and renal comorbidities 6
• Large volume of incompatible blood was transfused 6
• DAT is negative (indicating complete hemolysis) 6
• Plasma color is red 6
• Macroscopic hemoglobinuria is present 6

In one case series, 4 out of 5 geriatric patients with significant comorbidities recovered without incident when PE was performed early. 6

Long-Term Consequences

• Prolonged acute kidney injury requiring multiple hemodialysis sessions over weeks 5
• Kidney function may take 6 weeks or longer to return to near normal 5
• Alloimmunization to Rh antigens will occur if the patient survives, complicating all future transfusions 7, 3
• Risk of hemolytic disease of the fetus and newborn in Rh-negative women of childbearing potential who receive Rh-positive blood 3

Prevention of Future Alloimmunization

If the patient survives the acute reaction:

• Administer anti-D immunoglobulin (RhIG) within 72 hours at a dose of 20-25 mg (100-125 IU) per 1 mL of RBCs transfused if Rh-positive blood was given to an Rh-negative patient 3
• Obtain extended red cell antigen profile using genotyping (preferred over serology) for all future transfusions 4, 3
• Use extended antigen matching (C/c, E/e, K, Jka/Jkb, Fya/Fyb, S/s) for all subsequent transfusions to prevent additional alloimmunization 4, 3

Critical Pitfall to Avoid

Never transfuse ABO-incompatible blood under any circumstances—this causes immediate, severe hemolysis with high mortality and is never justified even in life-threatening anemia. 4 ABO compatibility takes absolute priority over all other blood group considerations. 4