ADAMTS13, TTP and Beyond

ADAMTS13, TTP and Beyond

ADAMTS13 (A Disintegrin And Metalloprotease with ThromboSpondin Type 1 repeats, 13), a plasma metalloprotease, cleaves von Willebrand factor (VWF) [1,2]. This cleavage is crucial for reducing the size of VWF multimers and adhesiveness, thereby preventing excessive platelet aggregation and thrombus formation at sites of vascular injury [3,4]. Deficiency of plasma ADAMTS13 activity could result i...

Acquired TTP: ADAMTS13 meets the immune system.

The majority of the patients affected by acquired thrombotic thrombocytopenic purpura (TTP) develop autoantibodies directed towards ADAMTS13 that interfere with its von Willebrand Factor (VWF) processing activity. B cell responses have been shown to primarily target the spacer domain of ADAMTS13 thereby prohibiting the binding of ADAMTS13 to the VWF A2 domain. In this review we summarize recent...

Degradation of two novel congenital TTP ADAMTS13 mutants by the cell proteasome prevents ADAMTS13 secretion.

INTRODUCTION Over 150 mutations have been identified in the ADAMTS13 gene in patients with congenital thrombotic thrombocytopenic purpura (TTP). The majority of these (86%), lead to reduced (<50%) secretion of mutant recombinant ADAMTS13. The mechanism by which this occurs has not been investigated in vitro. Two novel ADAMTS13 mutations (p.I143T and p.Y570C) identified in two congenital adolesc...

Clinical Policy Bulletin: ADAMTS13 Assay for Thrombotic Thrombocytopenic Purpura (TTP)

The role of ADAMTS13 in the new pathogenesis of TTP.

Thrombotic Thrombocytopenic Purpura (TTP) is a severe microvascular occlusive microangiopathy characterized by thrombocytopenia, Coombs-negative hemolytic anemia and ischemic symptoms localized mainly but not exclusively in central nervous system and resulting from diffuse platelet thrombi in microcirculation [1]. To understand the broad clinical spectrum of TTP it is important to read the orig...