2013 Volume 36 Issue 2 Pages 95-103
Thrombotic thrombocytopenic purpura (TTP) is a disorder caused by excessive platelet aggregation in multiple organs. Unless the patients are treated with plasma exchange, this disorder leads to early death. Recent studies show that TTP is caused by deficiency of a plasma metalloprotease ADAMTS13, which specifically cleaves von Willebrand factor (VWF). In the absence of ADAMTS13, unusually large VWF multimers (UL-VWFMs) released from endothelial cells are not cleaved appropriately, and cause platelet-rich microvascular thrombosis under high shear stress. Deficiency of ADAMTS13 is caused by autoantibodies against ADAMTS13 in patients with acquired TTP and mutations of the ADAMTS13 gene in congenital TTP. ADAMTS13 antibodies may inhibit enzymatic function or clear ADAMTS13 from circulation. Anti-ADAMTS13 antibodies are comprised predominantly of immunoglobulin class G (IgG). Epitope mapping studies showed that antibodies direct towards the spacer domain of ADAMTS13 are present in most patients with acquired TTP. The Spacer domain contributes to the binding of ADAMTS13 to unfolded VWF. Plasma exchange therapy for acquired TTP is effective because of removing ADAMTS13 autoantibodies and UL-VWFMs, and supply of ADAMTS13. In addition to plasma exchange, corticostroids are usually used for reducing the production of anti-ADAMTS13 antibodies. Recent studies have shown benefit in using rituximab as a first line therapy of acute acquired TTP.
