The role of ticlopidine in causing TTP is unknown, but an immune mechanism is possible [1, 2]. An autoantibody has been described that inactivates the protease that ordinarily cleaves high-molecular-weight von Willebrand factor. Persistence of high-molecular-weight von Willebrand factor may lead to platelet adhesion, aggregation, and the formation of platelet thrombi typical of TTP. Removal of the autoantibody has been associated with the return of protease activity and remission of TTP. Ticlopidine or a metabolite may induce such an autoantibody. In our report of 60 cases of TTP among patients who received ticlopidine, the syndrome generally occurred after 2 to 4 weeks of therapy, a period that is consistent with the temporal requirements for antibody induction. Furthermore, the infrequency of TTP in association with ticlopidine is in keeping with such immune idiosyncratic reactions to drugs, which occur only in certain susceptible patients.

In contrast, no evidence suggests that the overwhelming majority of TTP cases that are of unknown cause have an autoimmune component. In most of these cases, no causative event is clearly identifiable. Although controversial, it is of interest that long-term administration of ticlopidine may be of benefit in preventing TTP relapses and that additional studies are under way [3]. However, whether ticlopidine is an effective treatment for TTP is irrelevant to its role in provoking TTP. The situation may be analogous to the heparin-induced thrombocytopenia thrombosis syndrome [4]. Heparin is an effective treatment for thrombosis in most patients with this problem. However, a small number of patients develop heparin antibodies while receiving therapy, and continued administration of heparin results in recurrent, life-threatening venous and arterial thrombi.

Although the incidence of ticlopidine-associated TTP is unknown, it remains a serious and often fatal adverse drug effect. Physicians should be aware of the potential occurrence of the syndrome, especially in the short-term period after initiation of ticlopidine therapy. Early diagnosis and appropriate therapy with plasmapheresis can be life-saving. To date, no patient has been rechallenged with ticlopidine. In addition, no recurrences have been reported, suggesting that it is unlikely that long-term treatment with any antiplatelet agent, including ticlopidine, is required in these patients.