AIHA and Hypersensitivity Type III Quiz

AIHA and Hypersensitivity type III

• AIHA refers to autoimmune hemolytic anemia
• Hypersensitivity type III is a key component in the presentation of AIHA
• The presentation covers the normal development of red blood cells and their circulation
• It also covers different types of immune-mediated hemolytic reactions and how they can be detected via lab tests
• Specific learning objectives aim to explain red blood cell development and how it relates to intra and extra vascular destruction
• Understanding different immune hemolysis types and contrasting results from varied immune-mediated hemolytic reactions are also key objectives

Contents

• Normal red blood cell function, iron absorption, and re-absorption are detailed
• Pathology, pathophysiology, and signs/symptoms are discussed
• Laboratory interpretation of tests, with an emphasis on how blood samples may affect results, is explored

Normal Function of Red Blood Cells, Iron Absorption, and Re-absorption

• Red blood cell life cycle (including erythropoiesis)
• Iron absorption and re-absorption processes
• Iron toxicity and movement within the blood

Immune Haemolytic Anaemias

• Immune-mediated hemolytic reactions create specific and nonspecific patterns
• Specific antibodies are generated in relation to particular antigens
• Different types and forms of hemolysis are mediated by various antibodies
• Different drugs can interact with red blood cells, forming immune complexes and causing haemolysis

Immune Haemolytic Anaemia – Antibody Types

• Allo-antibodies (type II) are developed in response to other persons' cells
  • Can be triggered by pregnancy or transfusions (immediate or delayed reactions)
• Auto-antibodies (type II) are developed against the patient's own red cells
  • Can be primary (idiopathic) or secondary (due to malignancy or viral infection)
• Antibodies formed against drugs (type III) are developed due to exposure to specific drugs
  • This can lead to the creation of novel antigens

Warm or Cold AIHA

• Warm AIHA (IgG): extravascular haemolysis (destruction outside blood vessels)
  • IgG binds at 37°C (body temperature)
  • Gets removed by liver and spleen leading to bilirubin release
• Cold AIHA (IgM): intravascular haemolysis (destruction inside blood vessels)
  • IgM antibodies are activated at cooler temperatures
  • Results in hemoglobin release into the vascular system

Pathogenesis and Physiology

• Transfusion with incompatible blood can lead to B-cell/plasma cell derangement (e.g., myeloma/EBV infection)
• Familial predisposition can play a role in autoimmune disease conditions
• Complement-mediated destruction of red blood cells (IgG:C3b, IgM:MAC) is possible
• Intravascular hemolysis may lead to haemolysed blood, risk of disseminated intravascular coagulation (DIC), haemoglobinemia, and haemoglobinuria
• Extravascular hemolysis can cause jaundice, hepatosplenomegaly, and icterus

Patient Presentation

• Identical symptoms of immune-mediated hemolytic reactions include anaemia, pallor, and shortness of breath
• Different symptoms include jaundice and haemoglobinuria

Drug Adsorption Mechanism

• Hapten mechanism: drugs/metabolites adsorb onto red blood cell surfaces
• This leads to the production of drug-specific IgG alloantibodies
• Antibodies attach to drug coatings on red blood cells
• Extravascular haemolysis can result
• Lab findings often include a positive DAT (direct antiglobulin test)

Immune Complex Mechanism

• Anti-drug alloantibodies (IgM) bind to drugs in circulation
• Immune complexes attach to red blood cells
• Complement activation follows, leading to intravascular or extravascular haemolysis
• Can be severe/fatal, and can lead to 'innocent bystander' destruction; e.g., quinine, cephalosporins

Immune Complex Mechanism (Lab Findings)

• Hapten immune mechanism likely involved
• DAT positive test
• No antibodies detected in the lab investigation
• Positive results from incubating drug, serum, and reagent cells together

Membrane Modification Mechanism

• Drugs modify red blood cell membranes, leading to non-specific protein attachments
• This rarely causes haemolysis (e.g., cephalosporin)

Summary

• Defining different types of immune-mediated haemolysis
• Understanding how various antibodies modulate and mediate hemolysis
• Examining how specific drugs interact with red blood cells and cause immune complex-mediated haemolysis
• Investigating how sample presentation may affect testing results
• Diagnosing conditions via specific and non-specific antigram patterns are indicated

Laboratory Interpretation of Tests

• Understanding how sample presentation might affect test results
• Interpreting antigrams to identify specific antigens or underlying conditions
• Differentiating between IATs (indirect antiglobulin tests) and DATs (direct antiglobulin tests) for immune hemolysis diagnosis

How the Test Work

• IAT: Detects free antibodies in patient plasma using known red blood cells
• DAT: Identifies antibodies bound to red blood cells using known reagents

Reaction Scoring

• Scoring results of tests performed for different reactions to quantify the severity and type of reaction