The Changing Paradigm of Thrombotic Thrombocytopenic Purpura

ABSTRACT

New discoveries have changed a 20-year-old concept about the mechanism of microvascular thrombosis in thrombotic thrombocytopenic purpura (TTP). The classic model of TTP pathogenesis in which ultralarge von Willebrand factor (ULvWF) is proposed to mediate spontaneous platelet aggregation in high sheer stress has evolved into a model in which vWF-platelet aggregates form on stimulated endothelial cell surfaces. The classic model of TTP pathogenesis was based on the proposed pathogenicity of plasma ULvWF in TTP microvascular thrombosis. The current model suggests that platelet binding to endothelial-bound vWF and cleavage of endothelial-bound vWF-platelet aggregates may be most critical in TTP pathogenesis and treatment. A clearer understanding of the mechanism of microvascular thrombosis in TTP will allow better targeted treatment.

KEYWORDS

Thrombotic thrombocytopenic purpura (TTP) - von Willebrand factor (vWF) - ADAMTS13 - hemoglobin - platelets - microvascular thrombosis

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