Thrombotic Thrombocytopenic Purpura: Evidence That Infusion Rather Than Removal of Plasma Induces Remission of the Disease

Abstract

Plasma exchange has recently been reported to be more effective than plasma infusion for the treatment of thrombotic thrombocytopenic purpura (TTP). However, in the only available controlled study, the plasma infused during the exchange procedure was three times that given by infusion alone. Here we report the case of a patient with chronic relapsing TTP who had 21 relapsing episodes in the last 3 years. During 18 relapses, infusion of plasma, as infusion alone or in the context of an exchange procedure, invariably induced remission of the disease. By contrast, plasma removal alone (replaced with albumin and saline) was ineffective in three further consecutive relapses so that infusion was eventually necessary to induce remission. We concluded that the effective component of plasma exchange in TTP is infusion, rather than removal of plasma. Unusually large von Willebrand factor (ULvWF) multimers were found during both acute and remission phases, possibly reflecting intravascular leakage from ongoing endothelial cell injury. A relative increase of the 176-kd fragment and a relative decrease of the 225-kd subunit were demonstrated during the acute phase, indicating in vivo proteolytic vWF fragmentation. Since in vitro evidence is available that such fragments of vWF induce platelet aggregation, it is speculated that protease inhibitors of normal plasma help restore normal vWF processing activity in the circulation, which explains remission of the disease associated with the plasma infusion.