Pancytopenia azathioprine

Combined administration of azathioprine and allopurinol may result in severe pancytopenia. The dose of Azathioprine should be reduced by two-thirds when given with allopurinol. Azathioprine rarely causes liver dysfunction, frequently manifested by an isolated rise in ALT and bilirubin. With the introduction of mycophenolate mofetil, azathioprine may be relegated to a second-line anti metabolite for the prevention of graft rejection. 

Hematological toxicity is the most commonly reported severe adverse effect of azathioprine, and is marked by predominant leukopenia, thrombocytopenia, and pancytopenia (SED-13, 1120). In a 27-year survey of 739 patients treated with azathioprine 2 mg/kg for inflammatory bowel disease, dosage reduction or withdrawal of the drug because of bone marrow toxicity was necessary in 37 patients (5%) (11). There was moderate or severe leukopenia in 3.8% of patients in three patients pancytopenia resulted in severe sepsis or death. 

A number of other reports similarly describe reversible bone marrow toxicity associated with anaemia, pancytopenia, leucocytopenia and thrombocytopenia in patients given azathioprine with allopurinol, " and in one case a fatality occurred as a result of neutropenia and septicaemia. In a retrospective analysis of 24 patients who had received both azathioprine and allopurinol, 11 developed leucopenia, 7 developed moderate anaemia, and 5 developed thrombocytopenia. Only 14 of the patients had received a greater than two-thirds reduction in their azathioprine dose when allopurinol was started, but despite this, some of these patients still developed haematological toxicity." ... 

Chaparro M, Trapero-Marugan M, Mor-eno-Otero R, Gisbert IP. Azathioprine plus ribavirin treatment and pancytopenia. Aliment Pharmacol Ther 2009 30(9) 962-3. 

Liver A 48-year-old patient with Crohn s disease developed hepatic nodular regenerative hyperplasia, with fatigue, icterus, hepatosplenomegaly, and ascites, accompanied by pancytopenia fiver histology suggested a drug-induced cause and after withdrawal of azathioprine he improved substantially [128 ]. 

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