Can omeprazole cause thrombocytopenia?

Omeprazole and Thrombocytopenia: A Rare but Documented Association

Omeprazole can cause thrombocytopenia in rare cases, though it is not a common adverse effect and appears to be an individual drug reaction rather than a class effect of proton pump inhibitors (PPIs). 1

Evidence for PPI-Induced Thrombocytopenia

Case Reports and Causality

• Multiple case reports document thrombocytopenia associated with various PPIs:
  • Pantoprazole-induced thrombocytopenia has been reported with probable causality assessment using the Naranjo scale 2
  • Lansoprazole-induced thrombocytopenia has been documented in critically ill patients 3, 4
  • A case report showed thrombocytopenia when a patient was switched from omeprazole to pantoprazole, suggesting an individual drug effect rather than a class effect 1

Mechanism

• The mechanism is thought to be immune-mediated, though the exact pathogenesis remains unclear 1, 5
• Similar to other drug-induced thrombocytopenias, it likely involves antibody formation against platelets when the drug is present

FDA Label Information

• The FDA label for omeprazole lists hematologic adverse reactions including "agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis" as post-marketing observations 6
• These are listed as voluntarily reported adverse reactions where causality cannot always be reliably established due to uncertain population size

Clinical Implications

Risk Assessment

• Thrombocytopenia with PPIs appears to be extremely rare 1
• There is no evidence in major cardiovascular guidelines suggesting that omeprazole-induced thrombocytopenia is a significant clinical concern when prescribing for gastroprotection in patients on antiplatelet therapy 7
• The primary concern with omeprazole in clinical practice relates to potential drug interactions with clopidogrel rather than hematologic effects 7

Monitoring Recommendations

• Routine monitoring of platelet counts specifically for omeprazole-induced thrombocytopenia is not recommended in major guidelines
• For patients on PPIs who develop unexplained thrombocytopenia:
  1. Consider the PPI as a potential cause
  2. Evaluate for other common causes of thrombocytopenia
  3. Consider discontinuation of the PPI if no other cause is identified
  4. Monitor for recovery of platelet count after discontinuation

Cross-Reactivity Considerations

• Patients who develop thrombocytopenia with one PPI may not necessarily develop it with another 1, 4
• In one case report, a patient who developed thrombocytopenia with pantoprazole tolerated omeprazole without issues 1
• In another case, a patient who developed neutropenia with omeprazole also developed it with pantoprazole, suggesting possible cross-reactivity in some cases 5

Management Approach

If Thrombocytopenia Occurs

1. Discontinue the suspected PPI
2. Monitor platelet count for recovery
3. Consider alternative acid-suppressing medications (H2 receptor antagonists)
4. If a PPI is still indicated, consider cautious trial of a different PPI with close monitoring

Alternative Acid-Suppression Options

• H2 receptor antagonists (ranitidine, famotidine) may be considered as alternatives when a PPI-induced thrombocytopenia is suspected 7
• The FDA notes there is no evidence that H2 blockers or antacids interfere with antiplatelet activity of clopidogrel 7

Conclusion

While omeprazole can cause thrombocytopenia in rare instances, this is not a common adverse effect that should preclude its use in appropriate clinical scenarios. The benefit of gastroprotection in high-risk patients (such as those on dual antiplatelet therapy) typically outweighs this rare risk. If thrombocytopenia occurs and is suspected to be related to omeprazole, discontinuation and switching to an alternative acid-suppressing medication is recommended.