A case of thrombocytopenia caused by rifampicin and pyrazinamide
A 32-year-old male patient presented on 13/02/2012 in Department of General Medicine with complaints of fever since 1 month and history of antituberculosis treatment in 2002. On chest X-ray examination, the patient was found to have pleural effusion on the right side and was referred to Department of Pulmonary Medicine where 20 ml of straw-colored pleural fluid was aspirated. Pleural fluid was chiefly lymphocytic exudate with adenosine deaminase (ADA) 110 U/L, highly suggestive of tubercular pleural effusion. All routine investigations including complete hemogram, liver function tests (LFTs), renal function tests (RFTs), and complete urine examination were found within normal limits. On 17/02/2012, the patient underwent therapeutic tap with 1 L of straw-colored fluid removed from the pleural cavity and was put on three times a week Category II antituberculosis treatment under DOTS (streptomycin 750 g, isoniazid 600 mg, rifampicin 450 mg, ethambutol 1200 mg, and pyrazinamide 1500 mg) along with daily pyridoxine 10 mg at bed time. After about 20 days, on 10/03/2012, the patient presented in Department of Dermatology, Venereology & Leprosy (DVL) with complaints of ulceration in the mouth. Hemogram revealed hemoglobin (Hb) 8.3 gm%, total leukocyte count (TLC) 9800 cells/mm3, erythrocyte sedimentation rate (ESR) 45 mm/1 h, and platelet count 21,000/mm3. Peripheral smear revealed shift to left with thrombocytopenia, Prothrombin Time Index (PTI) 76.92% and International Normalized Ratio (INR) of 1.43. Enzyme-linked immunosorbant assay (ELISA) for human immunodeficiency virus (HIV) was negative, random blood sugar was within normal limits, and urine was also found normal.\nPatient was suspected of having thrombocytopenia due to rifampicin and was referred to the Department of Pulmonary Medicine where all drugs were stopped. On 21/03/2012, the ulcers healed, platelet count increased to 472,000/mm3, International Normalized Ratio (INR) was 1.82, and ESR was 30 mm/1 h. So, after taking informed consent, the patient was again started on the same regime, excluding rifampicin. Next day, the patient again had ulcers in the mouth and the platelet count decreased to 10,000/mm3. Treatment was again stopped and the patient recovered. One month later (on 19/04/2012), the patient returned for treatment. The platelet count (on 03/04/2012) was 505,000/mm3. It was decided that patient will be exposed to medicines one after the other. He was given only isoniazid 300 mg and the treatment was uneventful. On the third day, he was given 750 mg of pyrazinamide under observation. Within 24 h, the patient developed ecchymoses and ulcers in the mouth [] and the platelet count decreased to 23,000/mm3, forcing withdrawal of pyrazinamide; isoniazid (300 mg) was continued. Patient recovered, and so, believing that hypersensitivity was because of pyrazinamide and not because of rifampicin, after monitoring the platelet count, the patient was given rifampicin 150 mg along with isoniazid 300 mg on 26/04/2012. Within 6 h, the patient developed petechiae on legs and forearms [] and also fever with chills. Platelet count decreased to 25,000/mm3. Rifampicin was stopped and lesions subsided within 48 h. After 2 days, the patient was exposed to ethambutol and then to streptomycin uneventfully. Patient continued with isoniazid 300 mg, ethambutol 1000 mg, and streptomycin 750 mg without any further complaints.