Lesson 12

AIHA and Hypersensitivity Type III

Overview and Learning Objectives

  • Video Goals:

    • Cover the normal development of red blood cells (RBCs) and their lifecycle in circulation.

    • Explain the pathophysiology of immune-mediated hemolytic reactions.

    • Discuss how laboratory tests detect the pathophysiology of autoimmune and alloimmune hemolytic reactions.

  • Learning Outcomes:

    • Understand normal RBC development's role in intra- and extravascular destruction.

    • Describe various types of immune hemolysis.

    • Differentiate between results from various immune-mediated hemolytic reactions.

Contents of the Study

  1. Normal function of red cells, iron absorption, and re-absorption.

  2. Pathology, pathophysiology, signs, and symptoms of immune hemolytic anemia.

  3. Laboratory interpretation of tests related to immune hemolytic anemias.

Detailed Study of Red Cells and Hemolysis

Normal Function of Red Cells

  • Red Blood Cells (RBCs) Functions:

    • Deliver oxygen throughout the body.

    • Maintain flexibility to traverse capillaries.

Lifecycle of Erythrocytes

  • Development and Structure:

    • Erythrocyte membrane involves cholesterol and proteins that aid in pliability.

    • RBCs survive for 3-4 months in circulation.

    • Mature RBCs undergo changes leading to senescence (loss of flexibility).

  • Processes of Lysis:

    • Can occur through intravascular (within blood vessels) or extravascular (outside blood vessels) mechanisms.

Iron Metabolism

  • Utilization of Iron:

    • Iron exists as ferric (Fe³⁺) or ferrous (Fe²⁺) in the blood.

    • Toxicity risks and movement within the bloodstream are critical for hemoglobin function.

  • Bilirubin Handling:

    • Conjugated bilirubin is produced from the breakdown of hemoglobin, primarily processed by the liver.

    • Unconjugated bilirubin can lead to toxicity if not processed.

Pathology and Pathophysiology
Immune Hemolytic Anemias (AIHA Types)

  • Immune-mediated Hemolysis:

    • Antibodies can develop against red cell antigens:

    • Allo-antibodies: Developed in response to another person's cells (e.g., through transfusion, maternal-fetal interaction).

    • Auto-antibodies: Developed against one's own red blood cells, can be idiopathic or secondary (often due to malignancy or viral infections).

    • Drug-induced Hemolysis: Certain drugs can expose novel antigens on RBCs or create immune complexes.

Mechanisms of AIHA

  • IgG-mediated AIHA:

    • Associated with extravascular hemolysis; occurs at body temperature (37°C).

    • Results in the clearance of RBCs through the liver and spleen.

  • IgM-mediated AIHA:

    • Active at cooler temperatures; causes intravascular hemolysis by releasing hemoglobin into circulation.

Symptoms and Patient Presentation

  • Common Symptoms of Immune-mediated Hemolytic Reactions:

    • Similar Symptoms: Anaemia, pallor, shortness of breath.

    • Unique Symptoms: Jaundice, hemoglobinuria, which indicate hemolytic activity.

Laboratory Investigations
Testing Methods

  • Direct Antiglobulin Test (DAT):

    • Used to detect antibodies bound to RBCs. Useful for identifying hemolytic anemia due to autoimmune conditions.

    • Positive results indicate the presence of bound antibodies.

  • Indirect Antiglobulin Test (IAT):

    • Exposes known RBC phenotypes to patient plasma to detect free antibodies. Operates by using anti-human globulin (AHG) to identify antibodies bound to RBCs.

Understanding Test Results

  • Results Interpretation:

    • Scoring system:

    • 4+: Positive

    • 3+: Positive but lower than titre of 4

    • 2+: Moderate positive

    • 1+: Weak positive

    • 0: Negative

    • MF: Mixed field reaction, indicating a mixture of positive and negative results among different cell populations.

Drug-Induced Hemolytic Mechanisms

  • Adsorption Mechanism:

    • Drugs (e.g., penicillin) adsorbed onto RBC surfaces, leading to antibody production and extravascular hemolysis.

    • Laboratory findings: DAT positive, antibodies often not detected.

  • Immune Complex Mechanism:

    • Drug-specific alloantibodies produced can form immune complexes leading to cell destruction.

    • Severe cases may lead to intravascular or extravascular hemolysis.

  • Membrane Modification Mechanism:

    • Drugs modify RBC membranes, facilitating nonspecific attachment of proteins such as immunoglobulins, typically not causing hemolysis.

Summary of Key Terms and Concepts

  • AIHA Types:

    • Different antibodies modulate various forms of hemolysis, influenced by whether they are auto- or alloantibodies, and the mechanisms can include drug interactions.

  • Laboratory Tests:

    • IAT and DAT play crucial roles in diagnosing and managing immune hemolytic anemias. Test presentations strongly influence interpretative outcomes.

Conclusion

  • Comprehensive Understanding Required:

    • Knowledge about RBC development, hemolysis, symptoms, immune mechanisms, and laboratory test interpretation is essential for understanding immune hemolytic conditions.

  • Real-World Applications:

    • Enhances diagnostic accuracy and informs treatment decisions in hematological disorders.