The Hematologic Toxicity of Methotrexate in Patients with Autoimmune Disorders

Abstract

The incidence of auto-immune diseases is increasing nowa-days. Despite of the development of diagnosis and management of diseases, they remained chronic diseases. The patient's lifespan expansion requires long-term treatment with harmful agents, such as Methotrexate or other immuno-suppressive drugs. The Methotrexate toxicities are based on the duration and cumulative dosing of drug, and the combination with other drugs. Myelosuppression and consequent pancytopenia is the most frequent hematologic toxicity, which occur mostly later during low dose methotrexate administration.We demonstrate three cases of low dose Methotrexate toxicity in older patients with rheumatoid arthritis and psoriasis.All patients were treated with low dose Methotrexate along more than one year continuously.Two old patients with RA and another with psoriasis developed pancytopenia causing severe neutropenia, cutaneous bleeding, and bruising and septic condition. They required intravenous antibiotic therapy, corticosteroids and limited transfusion dependence as a result of low dose Methotrexate.We have assessed the possible causes of Methotrexate toxicities and found that all patients used non-steroid anti-inflammatory drugs because of pain and protonpump inhibitor to avoid development of peptic ulcer. Two patients recovered, another died in septic condition.We would like to drawn attention of hematologists, dermatologists and rheumatologists to the harmful effect of low dose methotrexate in this patient population and emphasize the role of rigorous and consequent hematologic testing to avoid these severe late complications.

Hubungan Pemilihan Obat dan Keberhasilan Terapi Pasien Rheumatoid Arthritis

“…Metotreksat bekerja dengan cara menghambat enzim pada jalur asam folat dengan menghambat biosintesis purin dan pirimidin sehingga terjadi gangguan replikasi DNA dan proliferasi sel. 22 Metotreksat dapat menyebabkan ganggun hematologi antara lain mielosupresi dan pansitopenia (trombositopenia, anemia megaloblastik dan leukopenia). 22 Efek samping dari metotreksat (anemia) yang dapat diprediksi menyebabkan penggunaan metotreksat selalu disertai asam folat.…”

“…22 Metotreksat dapat menyebabkan ganggun hematologi antara lain mielosupresi dan pansitopenia (trombositopenia, anemia megaloblastik dan leukopenia). 22 Efek samping dari metotreksat (anemia) yang dapat diprediksi menyebabkan penggunaan metotreksat selalu disertai asam folat. 19 Berdasarkan data yang diperoleh dalam penelitian ini, terlihat bahwa metotreksat merupakan jenis obat yang utama pada terapi pasien RA.…”

To err is…Drug? Patient? Doctor? Healthcare System?

“…These findings are similar to a case series report on methotrexate where pancytopenia was encountered as a later manifestation 8 and another case report which observed low dose methotrexate causing pancytopenia. 9 Once hematotoxicity is encountered, the drug is withheld, serum methotrexate levels are monitored and leucovorin rescue dosing is done to combat methotrexate effects. Granulocyte Colony stimulating factors will also be required where the patient has persistent pancytopenia.…”

Electrochemical Monitoring of Methotrexate Anticancer Drug in Human Blood Serum by Using in situ Solvothermal Synthesized Fe3O4/ITO Electrode

“…Iron oxide NPs samples were prepared using different methods including (i) coprecipitation methods in the presence or absence of sodium oleate; (ii) microwave assisted process, or (iii) solvothermal synthesis method. Figure 1a showed the XRD patterns of all as-prepared Fe 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 deposited of different Fe 3 O 4 NPs samples onto the ITO substrates based on the electrostatic attraction force between the positively charged Fe 3 O 4 NPs and the OH groups on the ITO surface [49].…”