Autoimmune Hemolytic Anemia (AIHA) - Part 1

Autoimmune Hemolytic Anemias

  • Autoimmune hemolytic anemias affect blood bank testing necessitating awareness for compatible units.

Definition of Autoimmune Hemolytic Anemia

  • Autoimmune hemolytic anemia is characterized by:

    • Immune hemolytic anemia: A condition where red blood cell survival is reduced due to a humoral immune response.

    • The humoral immune response is mediated by antibodies secreted by plasma cells.

    • It results in the self-destruction of one's own red blood cells leading to anemia.

Classification of Immune Hemolytic Anemias

  • Categories:

    • Alloimmune hemolytic anemia:

    • Antibodies produced against foreign red cell antigens.

    • Commonly occurs through:

      • Transfusion

      • Transplant

      • Pregnancy

    • Often leads to transfusion reactions.

    • Autoimmune hemolytic anemia:

    • Antibodies are produced in response to self-antigens, leading the body to treat its own cells as foreign.

    • Drug-induced hemolytic anemia:

    • Antibodies produced against a drug or drug complex.

    • Takes considerable effort to find compatible blood units due to the presence of underlying antibodies hidden by autoantibodies.

Immune Hemolysis Mechanism

  • Mechanism of Hemolysis:

    • Red blood cells are normal but may have antibodies or complement bound to their surface.

    • Most immune hemolysis occurs extravascularly in the spleen.

Diagnostic Testing

  • Direct Antiglobulin Test (DAT): Key test for assessing immune hemolysis.

    • Differentiates between IgG and complement sensitizing red blood cells in vivo.

    • A control tube is necessary when a positive result is present to validate the findings and rule out spontaneous agglutination.

    • Testing Strategy:

    • Perform polyspecific DAT first.

    • If positive, proceed with specific IgG and complement tests with controls.

  • A positive DAT indicates red cells coated with antibodies or complement, while demonstrating IgM is more challenging.

  • Elution Techniques:

    • When DAT results are ambiguous, elution techniques can be used to identify if antibodies coating erythrocytes are present.

Absorption Techniques

  • Absorption:

    • A method to isolate alloantibodies by removing autoantibodies from the patient’s plasma.

    • Types of Absorption:

    • Autologous Absorption:

      • Conducted using the patient's red blood cells.

      • Not recommended if the patient has been transfused recently.

    • Allogenic Absorption:

      • Utilizes reagent red cells from external sources, suitable for patients with recent transfusions or low supply of their own cells.

Clinical Features of Anemia

  • Symptoms:

    • Pallor (pale skin)

    • Fatigue

    • Tachycardia: Heart rate exceeding 100 beats per minute; risks include heart failure and stroke.

  • Diagnostic Labs:

    • Complete Blood Count (CBC): Includes measuring hemoglobin and hematocrit levels.

    • Reticulocyte count: Elevated in response to anemia signaling active red blood cell production.

    • Bilirubin levels: Elevated, especially indirect bilirubin indicating hemolysis.

    • Haptoglobin levels: Decreased due to hemolysis acting as a scavenger for free hemoglobin.

    • Lactate Dehydrogenase (LDH): Increased due to excess LDH in red blood cells during hemolysis.

    • Peripheral blood smear may show schistocytes and spherocytes indicating hemolysis.

Autoantibodies

  • Autoantibodies target the patient’s own red blood cells and must be identified accurately to determine differing treatments.

  • Classification:

    • Autoimmune hemolytic anemias can be classified as cold, warm, and drug-induced.

    • Warm Autoimmune Hemolytic Anemia:

    • Treatment typically includes corticosteroids or Rituximab.

    • Cold Autoimmune Hemolytic Anemia:

    • Usually benign but can become pathological requiring treatment in acute cases.

    • Drug-induced Autoimmune Hemolytic Anemia:

    • Identifying and discontinuing the offending medication is key to management.

Cold Autoantibodies

  • Types:

    • Benign Cold Autoantibodies:

    • Low titer typically at 4°C, potential transfusion only in life-threatening scenarios.

    • Pathological Cold Autoantibodies:

    • High thermal amplitude/titers often linked to disease, requiring treatment.

    • Reactive at body temperature, often IgM, activating complement and causing lysis.

Cold Hemagglutinin Disease

  • Chronic or acute hemolytic anemia due to cold antibody reaction.

  • Associations:

    • Infections (e.g., Mycoplasma pneumonia), malignancies like Chronic Lymphocytic Leukemia (CLL).

  • Signs of hemolysis:

    • Increased reticulocytes, decreased haptoglobin, and a positive DAT with complement.

Paroxysmal Cold Hemoglobinuria (PCH)

  • Characterized by red cell destruction due to an autoantibody that activates complement after binding at lower temperatures.

  • Commonly seen in children post-viral infections.

  • Key Laboratory Tests:

    • Positive Donath-Landsteiner test confirms diagnosis.

Treatment Strategies

  • Management of autoimmune hemolytic anemias varies:

    • Warm Autoantibodies: Often corticosteroids or specific therapies like Rituximab.

    • Cold Hemagglutinin Disease: Primarily supportive therapy; avoid cold exposure, and address complicating infections.

    • PCH: Treat underlying infections; otherwise supportive.

Conclusion

  • Comprehensive understanding of autoimmune hemolytic anemias, testing methodologies, classifications, and symptom recognition is crucial for effective diagnosis and treatment.