Methotrexate-induced pancytopenia: a case series of 46 patients

Int J Rheum Dis. 2017 Jul;20(7):846-851. doi: 10.1111/1756-185X.13004. Epub 2017 Mar 5.

Abstract

Aim: Methotrexate (MTX) has the potential to cause serious adverse reactions and even mortality. We analyzed the predisposing factors and outcome in patients with MTX-induced pancytopenia admitted into our unit from 1996 to 2015.

Methods: Patients were identified by departmental database search. Pancytopenia was defined as white blood cell count (WBC) < 3500 cells/mm3 , hemoglobin (Hb) < 11 g/dL and platelet count < 150 000 cells/mm3 . Severe pancytopenia was defined as WBC < 2000 cells/mm3 , Hb < 10 g/dL and platelet count < 50 000 cells/mm3 .

Results: Forty-six patients were included in the study (female = 35). Twenty-four had been under the care of either primary care physicians or orthopedic surgeons and presented to us with pancytopenia. Sixteen patients had severe pancytopenia. Disease distribution was as follows: rheumatoid arthritis 33, psoriasis eight, systemic sclerosis two and others three. The median dose of MTX was 10 mg/week and median duration of treatment was 11 months. The median cumulative dose was 750 mg. Symptoms at presentation included: oral mucositis (n = 37); fever (n = 24); diarrhea (n = 12), bleeding gums (n = 5) and purpura (n = 3). The potential risk factors were: hypoalbuminemia (n = 23), renal insufficiency (n = 14), dosing errors (n = 13) and non-supplementation of folates (n = 7). Thirteen patients died. WBC at admission was found to determine survival (P < 0.05).

Conclusion: In patients on MTX, oral mucositis and fever can herald pancytopenia. MTX-induced pancytopenia is associated with high mortality. WBC at admission is the most important prognostic factor. There is need for increased awareness among physicians to minimize prescribing errors. A national guideline on monitoring of patients on MTX is desirable.

Keywords: drug induced pancytopenia; methotrexate; methotrexate toxicity.

MeSH terms

  • Adult
  • Antirheumatic Agents / adverse effects*
  • Arthritis, Rheumatoid / diagnosis
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / mortality
  • Biomarkers / blood
  • Databases, Factual
  • Female
  • Hemoglobins / metabolism
  • Humans
  • Leukocyte Count
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Pancytopenia / blood
  • Pancytopenia / chemically induced*
  • Pancytopenia / diagnosis
  • Pancytopenia / mortality
  • Platelet Count
  • Psoriasis / diagnosis
  • Psoriasis / drug therapy*
  • Risk Factors
  • Scleroderma, Systemic / diagnosis
  • Scleroderma, Systemic / drug therapy*

Substances

  • Antirheumatic Agents
  • Biomarkers
  • Hemoglobins
  • Methotrexate