Venlafaxine-induced ecchymoses and impaired platelet aggregation

Objective: To describe a case of venlafaxine-induced ecchymoses.Methods: A patient with a history of ecchymoses coincident with venlafaxine therapy was rechallenged with the drug. Her platelet function was assessed with aggregation and ATP release studies before the rechallenge and after she developed ecchymoses. In addition, the effect of venlafaxine on platelet aggregation and ATP release was studied in vitro by adding the drug to platelet-rich plasma from normal donors. Results: After 4 wk of treatment with venlafaxine our patient developed extensive ecchymoses. At that time her platelet aggregation and release responses to epinephrine, ADP, collagen, and arachidonic acid were markedly suppressed. Adding venlafaxine to normal platelet-rich plasma also dramatically reduced the aggregation and release responses to the same agonists as well as to serotonin, but the concentrations of venlafaxine required were 1000-fold greater than those normally achieved clinically. Conclusions: Our patient demonstrated an idiosyncratic hypersensitivity to the platelet inhibitory effects of venlafaxine. Because venlafaxine is an inhibitor of serotonin uptake by platelets and neurons, this mechanism may contribute to the impact of this drug on platelet function. However, our in vitro studies suggest that this hypothesis is inadequate to explain the observations completely.