Hemolytic anemia classification

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Hemolytic anemia can be divided into intravascular and extravascular based on whether the destruction of RBC occurs in the vessels or outside the vessels usually in spleen and liver. Extravascular hemolytic anemia are commoner than intravascular. There are many types of hemolytic anemias and the general classification of hemolytic anemia is either acquired or inherited.

Classification

Types of Hemolytic Anemias

• Secondary immune hemolytic anemia
• Idiopathic autoimmune hemolytic anemia
• Non-immune hemolytic anemia caused by chemicals or toxins
• Microangiopathic hemolytic anemia (MAHA)
• Sickle-cell anemia
• Hemoglobin SC disease (similar in symptoms to sickle-cell anemia)
• Thalassemia
• Hemolytic anemia due to G6PD deficiency
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Hereditary elliptocytosis
• Hereditary ovalocytosis
• Hereditary spherocytosis
• Malaria
• Transfusion of blood from a donor with a different blood type

Hemolytic anemias can be either genetic or acquired.

Genetic

• Genetic conditions of RBC membrane
  • Hereditary spherocytosis
  • Hereditary elliptocytosis
• Genetic conditions of RBC metabolism (enzyme defects)
  • Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism)
  • Pyruvate kinase deficiency
• Genetic conditions of hemoglobin
  • Sickle cell anemia
  • Thalassemia

Acquired

Acquired hemolytic anemia can be further divided into immune and non-immune mediated.

Immune mediated hemolytic anaemia (direct Coombs test is positive)

• Autoimmune hemolytic anemia
  • Warm antibody autoimmune hemolytic anemia
    • Idiopathic
    • Systemic lupus erythematosus (SLE)
    • Evans' syndrome (antiplatelet antibodies and haemolytic antibodies)
  • Cold antibody autoimmune hemolytic anemia
    • Idiopathic cold hemagglutinin syndrome
    • Infectious mononucleosis and mycoplasma ( atypical) pneumonia
    • Paroxysmal cold hemoglobinuria (rare)
• Alloimmune hemolytic anemia
  • Haemolytic disease of the newborn (HDN)
    • Rh disease (Rh D)
    • ABO hemolytic disease of the newborn
    • Anti-Kell hemolytic disease of the newborn
    • Rhesus c hemolytic disease of the newborn
    • Rhesus E hemolytic disease of the newborn
    • Other blood group incompatibility (RhC, Rhe, Kidd, Duffy, MN, P and others)
  • Alloimmune hemolytic blood transfusion reactions (ie from a non-compatible blood type)
• Drug induced immune mediated hemolytic anemia
  • Penicillin (high dose)
  • Methyldopa

Non-immune mediated hemolytic anemia (direct Coombs test is negative)

• Drugs (i.e., some drugs and other ingested substances lead to hemolysis by direct action on RBCs)
• Toxins (e.g., snake venom)
• Trauma
  • Mechanical (heart valves, extensive vascular surgery, microvascular disease)
• Microangiopathic hemolytic anemia (a specific subtype with causes such as TTP, HUS, DIC and HELLP syndrome)
• Infections
  • Malaria
  • Babesiosis
  • Septicaemia
• Membrane disorders
  • Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood cell surface proteins)
  • Liver disease