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Methotrexate-related pancytopenia-factors that contribute to its development and outcomes

Sowmya Gopalan1, Datla Pravarshini1, Preetam Arthur1

  • 1Department of general medicine, Sri Ramachandra Institute of Higher Education and Research, SRIHER, Porur, Chennai, India.

Tropical Doctor
|June 2, 2026
PubMed

Insights

Low-dose methotrexate can cause pancytopenia, especially when taken daily instead of weekly. Patient education and careful monitoring in elderly patients or those with renal failure can help prevent this rare but serious side effect.

Area of Science:

  • Rheumatology
  • Hematology
  • Pharmacology

Background:

  • Methotrexate is a widely used disease-modifying anti-rheumatoid drug.
  • Bone marrow suppression and pancytopenia are rare but serious adverse effects of methotrexate.
  • Understanding the factors contributing to methotrexate-induced toxicity is crucial for patient safety.

Purpose of the Study:

  • To retrospectively analyze patients experiencing pancytopenia after low-dose methotrexate intake.
  • To identify factors associated with the development, clinical features, and outcomes of methotrexate toxicity.
  • To evaluate strategies for mitigating methotrexate-related adverse events.

Main Methods:

  • Retrospective analysis of patients admitted with pancytopenia following low-dose methotrexate between 2019 and 2025.
  • Evaluation of patient demographics, dosing errors, comorbidities, and treatment outcomes.
  • Assessment of the role of Folinic acid rescue and transfusion support.

Main Results:

  • Early toxicity was frequently linked to inadvertent daily methotrexate dosing instead of weekly.
  • Delayed toxicity was associated with renal failure, advanced age, and hypoalbuminemia.
  • Folinic acid rescue was administered to all patients; 20% required transfusion support.
  • Two patients died due to neutropenia-related sepsis.

Conclusions:

  • Incorrect methotrexate dosing (daily vs. weekly) is a significant risk factor for early toxicity.
  • Renal impairment, age, and hypoalbuminemia contribute to delayed methotrexate toxicity.
  • Enhanced patient education on correct dosing and regular monitoring, especially for high-risk groups, can reduce methotrexate-induced pancytopenia.
Keywords:
Methotrexatedevelopmentmedication erroroutcomespancytopenia

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