Rifampicin thrombocytopenia

Reports of drug-induced thrombocytopenia have been systematically reviewed (1). Among the 98 different drugs described in 561 articles the following antibiotics were found with level I (definite) evidence co-trimoxa-zole, rifampicin, vancomycin, sulfisoxazole, cefalothin, piperacillin, methicillin, novobiocin. Drugs with level II (probable) evidence were oxytetracycline and ampicillin. 

A 300 mg dose of rifabutin is usually well tolerated. Adverse effects include neutropenia, thrombocytopenia, rash, and gastrointestinal disturbances (nausea, flatulence). Myositis (12) and uveitis (13) are rarely observed. The drug-induced lupus-like syndrome has been linked in a few cases with rifampicin and rifabutin. 

Hemolysis (34,35), agranulocytosis (36), leukopenia (37), and thrombocytopenia (38) have been reported in patients taking rifampicin (SED-10, 578) and constitute contraindications to continuation of therapy. 

Immune thrombocytopenia during rifampicin therapy has been attributed to drug-dependent binding of an IgG antibody to platelets the binding epitope of the antibody was found in the glycoprotein Ib/IX complex (38). 

Pereira J, Hidalgo P, Ocqueteau M, Blacutt M, Marchesse M, Nien Y, Letelier L, Mezzano D. Glycoprotein Ib/IX complex is the target in rifampicin-induced immune thrombocytopenia. Br J Haematol 2000 110(4) 907-10. 

Intermittent exposures have also been used with rifampicin (with 1-3 single exposures a week) and seemed to enhance markedly the otherwise extremely rare appearance of an acute thrombocytopenia. If exposure is sporadic, valuable epidemiological studies cannot usually be realised. 

Berte SJ, Di Mase ID, Christianson CS (1964) losoniazid para-aminosalicylic acid and streptomycin intolerance in 1,714 patients. Am Rev. Respir Dis 90 598-606 Blajchman MA, Lowry RC, Pettit JE, Stradling P (1970) Rifampicin-induced immune thrombocytopenia. Br Med J 3 24-26... 

Muhlberger (1973) saw a case of granulocytopenia in which the patient made a full recovery. Haegi (1975) observed a reproducible drug fever after treatment with ethambutol. He saw thrombocytopenia and pancytopenia only with the combination of ethambutol and rifampicin. 

Hemolytic anemia associated with rifampicin was hypothesized to be hapten mediated, as the patient s serum fixed complement in the presence of rifampicin. However, subsequent studies identified circulating erythrocyte-specific antibodies in the serum with specificity for both the Lutheran (Lu) and I antigens. The presence of the I antigen on the surface of leukocytes, platelets, and renal tubular epithelial cells may have accounted for the hemolysis, thrombocytopenia, and renal failure with acute tubular damage observed in the first patient. 

In the case of rifampicin-associated thrombocytopenia described by Lupo et at. (21 ) no antiplatelet antibodies were observed and the authors regarded the effect as a direct toxic action on the marrow rather than one mediated by immunological means. 

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