Abnormal platelet aggregation associated with fluoxetine therapy.

OBJECTIVE: To document the development of abnormal hemostasis in a patient treated with fluoxetine. CASE SUMMARY: A 49-year-old man developed a release-type defect in platelet aggregation during treatment with fluoxetine. Abnormal platelet aggregation was observed during platelet viability testing, in which adenosine diphosphate, epinephrine, ristocetin, arachidonic acid, and collagen were used as agonists. Two days after the withdrawal of fluoxetine, platelet function returned to normal. DISCUSSION: Fluoxetine is an antidepressant that is thought to act through inhibition of serotonin reuptake in the central nervous system. Fluoxetine also inhibits the reuptake of serotonin in platelets, significantly decreasing granular storage and potentially influencing platelet aggregation characteristics. Clinical manifestations of abnormal platelet function have been reported in association with fluoxetine therapy. CONCLUSIONS: The rapid normalization of platelet aggregation after the withdrawal of fluoxetine in this patient does not conform to the known clinical pharmacokinetics of norfluoxetine. The half-life of fluoxetine is shorter, suggesting that the parent drug (rather than norfluoxetine) was the causative agent. Serum fluoxetine and norfluoxetine concentrations were not measured in this patient.

Prospective evaluation of a flexible protocol for starting treatment with warfarin and predicting its maintenance dose.

We have evaluated a flexible warfarin dose induction protocol by monitoring its performance in 100 elderly inpatients. The protocol (designed by Fennerty et al., has two aims: (a) to move the prothrombin time (PT) ratio smoothly and quickly into its therapeutic range, and (b) to predict the steady-state warfarin requirement from the PT ratio measured on the fourth treatment day. It proved simple to use and reasonably successful, since after four days, 67/100 patients had achieved a therapeutic level of PT ratio, nine exceeded the therapeutic range, and 24 remained sub-therapeutic, while none had bled due to excessive anticoagulation. Maintenance dose prediction was tested by comparing the predicted and observed maintenance doses in patients within the 'therapeutic range' of PT ratio after various median times of treatment. After ten days, the observed dose was within 1 mg of that predicted in 65/86 patients (76%). This proportion became 57/77 (74%) after 18 days, and 49/79 (62%) after 34 days.