Hemolytic anemia causes

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Shyam Patel [2]

The causes for hemolytic anemia can be divided into intracorpuscular or extracorpuscular causes. The intrinsic causes are commonly due to hereditary causes whereas the extrinsic causes are commonly acquired. Drugs are another major cause of hemolysis. In the era of immunotherapy for cancer, drug-related causes are becoming increasingly important to recognize.

The causes of hemolytic anemia can be divided into etiologies that are intrinsic to red blood cell biology or extrinsic to red blood cell biology. Intrinsic, or intracorpuscular, causes include red blood cell membrane defects or enzyme deficiencies. Extrinsic causes include infections, autoimmune conditions, or drugs.

• Paroxysmal nocturnal hemoglobinuria
• Alpha thalassemia
• Hereditary spherocytosis: This is the most common hereditary form of hemolytic anemia.^[1] It is caused by mutations in red blood cell cytoskeletal proteins, such as:
  • Spectrin
  • Ankyrin
  • Band 3
  • Band 4.1
  • Glycophorin
• Hereditary elliptocytosis
• Unstable hemoglobin variants and hemoglobinopathies

• Glucose-6-phosphate dehydrogenase deficiency
• Pyruvate kinase deficiency
• Triose phosphate isomerase deficiency

Extrinsic factors refers to those that are commonly acquired in nature and have an adverse effect on red blood cells.

• Shiga-toxin from enterohemorrhagic E. coli strain O157:H&
• Parvovirus
• Malaria
• Babesia
• Clostridium perfringens

Systemic activation of the immune system due to underlying rheumatologic conditions can result in a predisposition for hemolysis.

• Systemic lupus erythematosus

These are important causes of hemolysis, especially in the era of immunotherapy for cancer. As more immunotherapeutic agents reach the market, it is likely that there will be more cases of iatrogenic hemolytic anemia.

• Pembrolizumab
• Nivolumab
• Ipilimumab
• Durvalumab
• Avelumab
• Dapsone
• Quinines

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