Hemolytic anemia is anemia due to hemolysis, the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either acquired or inherited. Treatment depends on the cause and nature of the breakdown.

Overview

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Normally, a red blood cell survives 90 to 120 days in circulation: about 1% of human red blood cells break down each day, which matches the production rate. The spleen (via the reticulo-endothelial system) is the primary organ by which red blood cells are cleared out of the circulation.

When the rate of breakdown increases, the body compensates by producing more red blood cells. If compensation is adequate there are few clinical problems.

If breakdown occurs at such a rate that it exceeds the body's ability to keep up, anemia develops.

Symptoms

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Signs of anemia are generally present (fatigue, later heart failure). Jaundice may be present.

• certain aspects of the medical history can suggest a cause for hemolysis (drugs, fava bean or other sensitivity, prosthetic heart valve, or other serious medical illness)

Tests

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• Peripheral blood smear microscopy:
  • fragments of the red blood cells ("schistocytes") can be present
  • some red blood cells may appear smaller and rounder than usual (spherocytes)
  • reticulocytes are present in elevated numbers. This may be overlooked if a special stain is not used.
• The level of bilirubin in the blood is elevated. This may lead to jaundice.
• The level of lactate dehydrogenase (LDH) in the blood is elevated
• Haptoglobin levels are decreased
• The direct Coombs test is positive, if hemolysis is caused by an immune process.

Classification of hemolytic anaemias

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Causes of haemolytic anaemis 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 haemoglobin
  • Sickle cell anaemia
  • Thalassaemia

Acquired

Acquired haemolytic anaemia 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
      • 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
      • Other blood group incompatibility (RhC, Rhe, RhE, Kidd, Duffy, MN, P and others)
    • Alloimmune hemolytic blood transfusion reactions (ie from a non-compatible blood type)
  • Drug induced immune mediated hemolytic anaemia
    • Penicillin (high dose)
    • Methyldopa
• Non-immune mediated haemolytic anaemia (direct Coombs test is negative)
  • Drugs (i.e., some drugs and other ingested substances lead to haemolysis 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
    • Septicaemia
  • Membrane disorders
    • Paroxysmal nocturnal hemoglobinuria (rare acquired clonal disorder of red blood cell surface proteins)
    • Liver disease

Drug induced hemolysis

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Drug induced hemolysis has large clinical relevance. It occurs when drugs actively provoke red cell destruction by either immune or non-immune mechanisms.

Immune

Penicillin in high doses can induce immune mediated hemolysis via the 'drug absorption hapten (immune) mechanism' whereby antibodies are targeted against the red blood cell and complement is activated leading to the removal of red blood cells by the spleen.

Non-immune

Non-immune drug induced hemolysis can occur via oxidative mechanisms. This is particularly likely to occur when there is an enzyme deficiency in the antioxidant defence system of the red blood cells. An example is where antimalarial oxidant drugs like primaquine damage red blood cells in Glucose-6-phosphate dehydrogenase deficiency.

Some drugs cause RBC lysis even in normal individuals. These include dapsone and sulfasalazine.

Differential diagnosis

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• Ineffective hematopoiesis is sometimes misdiagnosed as hemolysis.
  • Clinically these conditions may share may features of hemolysis
  • Red cell breakdown occurs before a fully developed red cell is released into the circulation.
  • Examples: thalassemia, myelodysplastic syndrome
• Megaloblastic anemia due to deficiency in vitamin B12 or folic acid.

Therapy

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Definitive therapy depends on the cause.

• Symptomatic treatment can be given by blood transfusion, if there is marked anaemia.
• In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
• Sometimes splenectomy can be helpful where extravascular heamolysis is prodominant (ie most of the red blood cells are being removed by the spleen).

Blood disorders | Hematology

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