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Mild intravasal haemolysis associated with flu-syndrome during intermittent rifampicin treatment.

Sixteen patients were given high-dose intermittent rifampicin treatment (900 mg twice weekly) in order to record side-effects of the flu-type. Three patients who experienced a febrile reaction were re-challenged under strict hospital supervision with a single dose (900 mg) of rifampicin. Two patients showed a distinct febrile response together with rapidly subsiding symptoms typical of the rifampicin-induced flu-syndrome, whereas the third patient's reaction was clinically different. During the challenge, the changes in a number of laboratory tests were indicative of a mild haemolytic reaction in the two patients with flu-syndrome. Plasma haemoglobin steeply increased within a few hours following the ingestion of the dose. This was associated with an acute increase in the total bilirubin and with a gradual decrease in the blood haemoglobin and haematocrit values. In further support of a drug-induced haemolysis was the findings that both patients showed a distinct reticulocyte response several days after the challenge. No such changes were seen in the third patient, whose reaction was later demonstrated to be related to isoniazid. The flu-syndrome thus may represent a first warning sign of intravasal haemolysis, which, if massive enough, eventually could lead to haemolytic crises and renal failure.