Cold Agglutinin Disease Quiz

Haemolytic Anaemia

• Haemolytic anaemia is a condition where red blood cells (RBCs) are destroyed prematurely, leading to a deficiency of these cells in the blood.
• This premature destruction can be caused by intrinsic RBC defects (e.g., haemoglobin, enzyme, or membrane defects) or extrinsic factors (e.g., autoimmune diseases, vascular defects, toxins, or heat).
• Intravascular haemolysis occurs when RBCs are directly destroyed within the blood vessels.
• Extravascular haemolysis happens when intact but abnormal RBCs are phagocytosed by macrophages in the spleen and liver.

Learning Objectives

• Red blood cell enzyme pathways and possible deficiencies.
• Basic structure of the red blood cell membrane.
• Defects in the red blood cell membrane (both congenital and acquired).

Classification of Haemolytic Anaemia

• Categorization based on whether the defect lies outside or inside the red blood cell (RBC).
• Immune haemolytic anaemia (DAT positive): Further categorized based on the type of antibody (warm, cold, mixed).
• Non-immune haemolytic anaemia (DAT negative): The defect lies inside the RBC.

Pathophysiology

• The breakdown of red blood cells—the process by which bilirubin and other byproducts are produced.
• The various pathways for the processing and excretion of these byproducts.
• The roles of the liver, spleen, and bone marrow in the process.

Blood Film Clues

• Bite cells, blister cells, or irregularly shaped red blood cells (poikilocytosis) suggest oxidative haemolysis.
• Spherocytes or microspherocytes suggest immune haemolysis.
• Schistocytes suggest thrombotic microangiopathy.

Autoimmune Haemolytic Anaemia (AIHA)

• Autoimmune-mediated destruction of red blood cells (RBCs) by autoantibodies.
• Properties and target specificities of the autoantibodies vary.
• Classification as primary (no obvious cause) or secondary (caused by an underlying condition, like lymphoma, infection, or medication).
• Co-existence with autoimmune thrombocytopenia (Evan's syndrome).
• Haemolysis initiated when autoantibodies bind to the RBC membrane, which triggers complement activation or other mechanisms.
• RBC destruction through extravascular or intravascular pathways.

Warm Antibody Haemolytic Anaemia

• Warm AIHA is due to IgG antibodies active at normal body temperature.
• Antibodies react with RBC antigens at warmer temperatures.
• Primary or secondary to an underlying condition (e.g., lymphoma).
• Antibodies frequently bind to all RBCs in a reaction called panagglutination.

Cold Antibody Haemolytic Anaemia (CAHA)

• Pathophysiology of CAHA is characterized by IgM antibodies reacting with RBCs at low temperatures, resulting in their extravascular lysis.
• The antibodies typically target the I or i blood group antigens.
• Titer (the concentration of the antibody) generally above 32 is clinically significant.

Paroxysmal Cold Haemoglobinuria (PCH)

• Uncommon autoimmune haemolytic anaemia where antibodies bind to red blood cells at cold temperatures, fixing complement, and leading to intravascular haemolysis.
• Characterised by Donath-Landsteiner antibodies, which react to RBCs at cold temperatures, leading to complement-mediated damage.

Drug-Induced Haemolytic Anaemia

• Immune mechanisms: Antibiotics, diclofenac, and certain chemotherapeutic agents.
• Oxidative mechanisms: Primaquine, dapsone, and some other drugs.
• Specific drug examples (table provided).
• Methæmoglobinemia: Some antibiotics and other drugs.
• Thrombotic microangiopathy: Certain drugs.

Inherited Haemolytic Anaemias

• Red blood cell membrane defects: Hereditary spherocytosis, hereditary elliptocytosis, pyropoikilocytosis (including cases of hereditary spherocytic elliptocytosis).
• Hereditary elliptocytosis (HE) and pyropoikilocytosis (HPP): Genetic disorders characterized by abnormal red blood cell shapes (elliptocytes, spherocytes).

Microangiopathic Haemolytic Anaemia (MAHA)

• A non-immune hemolytic disorder where red blood cells are fragmented due to abnormal blood vessel structure or function.
• Caused by various conditions (thrombotic thrombocytopenic purpura, hemolytic uremic syndrome).
• Key feature is schistocytes and fragmented red blood cells on examination (blood film).

Thrombotic Thrombocytopenic Purpura (TTP)

• Caused by deficient ADAMTS13 activity resulting in clotting factors, VWF build-up, microthrombi formation, and eventually red blood cell damage.
• Diagnosis relies on clinical symptoms and laboratory findings which include abnormal blood test results.

Case Studies

• Provided case details including symptoms, investigations, and likely diagnoses.