Abstract | April 20, 2023
Life threatening hematologic emergency from low dose methrotrexate
Learning Objectives
- Identify patients on drugs like methotrexate before prescribing other new medications, that may increase likelihood of drug accumulation/toxicity, especially in the setting of AKI risk factors.
- Treat Methotrexate toxicity by discontinuing the drug, maintaining normal hemodynamics, timely transfusions. Leucovorin also called folinic acid bypasses the metabolic block induced by MTX, and must be initiated as soon as possible for life-threatening myelopsupression as described in the case above.
- Implement the practice to routinely monitor the labs while patients are on methotrexate therapy. As per ACR, routine blood work should be performed every 4 weeks during first three months of therapy, every 8 to 12 weeks from 3 to 6 months, and every 8-12 weeks thereafter.
Introduction: Methotrexate (MTX) is an inhibitor of cellular proliferation and is used in the treatment of several rheumatic, auto-immune, malignant conditions at variable doses. In comparison to high doses mainly used for malignancies, when given at the standard 7.5-25 mg weekly dose for RA, adverse drug reactions are rare. However, hypoalbuminemia, age, malnutrition, renal failure, and polypharmacy may attribute to developing MTX toxicity resulting in gastrointestinal upset, hepatoxicity, neurotoxicity, myelosuppression etc just as high doses. Literature review shows only few reported cases reflecting low dose methotrexate associated emergencies. Here we present a case of life threatening pancytopenia caused by low dose MTX, because of renal failure.
63-year-old female came to the ER with chief complaints of nausea, vomiting, shortness of breath, palpitations, weakness for 2 weeks, an episode of nose bleed the day of presentation. Past medical history significant for rheumatoid arthritis managed with folic acid and methotrexate 2.5 mg 5 tabs am, 5 tabs pm once weekly, with last dose taken a week prior to admission. Recent 2-week history of oral thrush, and UTI treated with fluconazole and ciprofloxacin, respectively. Upon presentation her BP was 97/49, HR was 105, saturating 93% on room air with RR of 20. On physical exam, she appeared frail, pale, with generalized bruising and petechiae over anterior chest, and extremities. Her labs showed WBC count 0.7, hemoglobin 3.8, platelet count 1, BUN 80, creatinine 2.9, ALP 59, AST 29, ALT 35, GFR 16, magnesium 1.8, proBNP 432, troponin negative, COVID negative, lactate 5.6. Chest x-ray and CT head were normal. CT abdomen/pelvis without contrast showed hepatic steatosis. She was given IV fluids, antibiotics, then required levophed support. Blood and urine cultures did not show any growth
Final Diagnosis: Severe pancytopenia secondary to methotrexate toxicity, exaggerated by AKI with the recent use of Ciprofloxacin.
Management: Methotrexate was discontinued. Patient was treated with 3 units of PRBCs, 4 units of platelets and leucovorin 15 mg every 6 hours for 4 days. Subsequently her labs and symptoms improved and was discharged home after 1 week of hospital stay.
References
Kanderi T, Chan Gomez J, Puthenpura MM, Yarlagadda K, Gangireddy M. Pancytopenia as a Complication of Low-Dose Methotrexate in a Septuagenarian: A Rare Presentation. Cureus. 2020;12(6):e8492. Published 2020 Jun 7. doi:10.7759/cureus.8492
Pu T, Ni Y, Li PH, Yu D, Yu Q, Yu LM. Pancytopenia after Low-Dose Methotrexate Therapy in Two Hemodialysis Patients with Rheumatoid Arthritis. Am J Med Sci. 2022;363(2):185-190. doi:10.1016/j.amjms.2021.08.008
Hassan SWU. Pancytopenia Resulting From Low-Dose Methotrexate Use: A Diagnostic Challenge. Cureus. 2021;13(5):e15193. Published 2021 May 23. doi:10.7759/cureus.15193
