Most Common Causes of Hemolysis
The most common causes of hemolysis include immune-mediated mechanisms, glucose-6-phosphate dehydrogenase (G6PD) deficiency, microangiopathic conditions, infections, and drug-induced hemolysis. These etiologies can be broadly categorized as either acquired or hereditary causes of premature red blood cell destruction.
Diagnostic Approach to Hemolysis
When evaluating hemolysis, laboratory findings typically include:
- Anemia with reticulocytosis
- Increased lactate dehydrogenase (LDH)
- Elevated unconjugated bilirubin
- Decreased haptoglobin
- Characteristic findings on peripheral blood smear
Acquired Causes of Hemolysis
1. Immune-Mediated Hemolysis
- Autoimmune hemolytic anemia (AIHA): Associated with malignancies, autoimmune disorders, and medications 1
- Alloimmune hemolysis: Transfusion reactions, hemolytic disease of the fetus and newborn 2
- Drug-induced immune hemolysis: Can occur with various medications through different mechanisms 1
2. Microangiopathic Hemolytic Anemia (MAHA)
- Thrombotic thrombocytopenic purpura (TTP)
- Hemolytic uremic syndrome (HUS)
- Disseminated intravascular coagulation (DIC)
- Malignant hypertension
- Mechanical heart valves 3, 1
3. Infectious Causes
4. Drug-Induced Hemolysis
Common medications include:
- Ribavirin
- Rifampin
- Dapsone
- Interferon
- Cephalosporins
- Penicillins
- NSAIDs
- Quinine/quinidine
- Fludarabine
- Ciprofloxacin 2
5. Other Acquired Causes
- Direct physical trauma to RBCs
- Burns
- Hypersplenism
- Liver disease
- Sepsis/shock 3
Hereditary Causes of Hemolysis
1. Enzyme Deficiencies
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Most common enzymatic defect, particularly in individuals of African, Mediterranean, or Southeast Asian descent. Hemolysis typically occurs after exposure to oxidant drugs or during infections 2
- Pyruvate kinase deficiency: Characterized by chronic hemolytic anemia with variable severity 2
2. Membrane Disorders
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Hereditary stomatocytosis 1
3. Hemoglobinopathies
Special Considerations
G6PD Deficiency
G6PD deficiency is particularly important to recognize as it's one of the most common causes of hemolysis worldwide. The GdA- variant is found in 10-15% of Black men and women, while the Gdmed variant is more common in individuals from the Mediterranean, India, and Southeast Asia. The Gdmed variant can cause life-threatening hemolysis, while GdA- typically causes milder, self-limited hemolysis 2.
Immune Checkpoint Inhibitor-Related Hemolysis
With increasing use of immunotherapy, it's important to recognize immune-related adverse events including autoimmune hemolytic anemia. This requires prompt recognition and management with corticosteroids and potentially other immunosuppressive agents 2.
Clinical Pearls and Pitfalls
Don't miss drug-induced hemolysis: Always consider medications as potential triggers for hemolysis, especially in patients with G6PD deficiency exposed to oxidant drugs.
Peripheral blood smear is crucial: The morphology of red blood cells can provide important diagnostic clues (e.g., spherocytes in hereditary spherocytosis or AIHA, schistocytes in MAHA).
Consider both intravascular and extravascular hemolysis: Intravascular hemolysis presents with hemoglobinemia, hemoglobinuria, and hemosiderinuria, while extravascular hemolysis typically does not.
Remember less common causes: In cases where common etiologies have been ruled out, consider rare causes such as paroxysmal nocturnal hemoglobinuria (PNH), Wilson's disease, or other metabolic disorders.
Screening for G6PD deficiency: This is recommended before starting oxidant drugs in patients with predisposing racial or ethnic backgrounds 2.
By systematically evaluating patients with suspected hemolysis and considering both acquired and hereditary causes, clinicians can establish the correct diagnosis and implement appropriate management strategies.