Antiplatelet therapy in thrombotic thrombocytopenic purpura

Abstract

The presence of platelet-fibrin microthrombotic occlusions in the arterioles and capillaries of involved tissues of patients with TTP has suggested a role for platelet aggregation in this disorder. Inhibitors of platelet aggregation have been reported to produce resolution of thrombocytopenia and clinical improvement in many instances. Failure of such agents to produce a clinical effect has been attributed to inadequate dose-duration, severity and extent of end organ/vascular involvement, long-term or secondary effects of the etiologic principal leading to patient deterioration and/or demise. On the other hand, the parallel use of several treatment modalities that themselves may produce clinical effect confounds the interpretation that anti-platelet agents alone may have been responsible for clinical improvement. Nonetheless, complete remission has been reported in a number of TTP patients when the combination ASA/dipyridamole was used alone or together with plasmapheresis, splenectomy, and/or other antiplatelet agents. The evidence for a beneficial clinical effect would seem strongest for the use of this combination early in the course of the disease. More limited and less conclusive has been the experience with sulfinpyrazone, with ticlopidine, and with intravenous PGI2 infusions in TTP. Reports of clear-cut benefit with each of these agents have been rare. Finally, serial dextran infusions have apparently produced amelioration of the clinical syndrome in certain individuals. Assessment of benefit of dextran infusions from retrospective series has been limited by antecedent use of splenectomy. The use of red cell and plasma infusions during splenectomy has been argued to provide some benefit. However, it is likely that dextran can produce definite responses in certain patients. Unfortunately, therapeutic efficacy has been judged from such anecdotal reports and retrospective series. No prospective controlled trials of any of these approaches are available.