Diagnostic relevance of ADAMTS13 activity: Evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis (original) (raw)

Thrombotic Thrombocytopenic Purpura: A Thrombotic Disorder Caused by ADAMTS13 Deficiency

Hematology/Oncology Clinics of North America, 2007

A serious disorder with characteristic microvascular thrombosis involving the brain and other organs, TTP typically presents with thrombocytopenia, hemolysis with schistocytes on blood smears and mental changes or seizures and may rapidly progresses to a fatal end if the patients are not immediately treated with plasma. Recent advances have shown that TTP is caused by deficiency of a circulating, von Willebrand factor cleaving metalloprotease, ADAMTS13. This new knowledge will provide clues to improve the diagnosis and management of this intriguing disease.

Von Willebrand Factor, ADAMTS-13, and Thrombotic Thrombocytopenic Purpura

Seminars in Thrombosis and Hemostasis, 2010

Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tis-sue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency.

ADAMTS13 Secretion and Residual Activity among Patients with Congenital Thrombotic Thrombocytopenic Purpura with and without Renal Impairment

Clinical journal of the American Society of Nephrology : CJASN, 2015

Acute renal impairment is observed in 11%-23% of patients with congenital thrombotic thrombocytopenic purpura (TTP) and deficiency of a disintegrin and metalloprotease with thrombospondin motifs 13 (ADAMTS13, a metalloprotease that cleaves von Willebrand factor [VWF] multimers), a substantial percentage of whom develop CKD during follow-up. Here we investigated whether, in 18 patients with congenital recruited from 1996 to 2013 who fulfilled inclusion criteria, acute renal involvement occurred during bouts segregated with lower secretion and activity levels of ADAMTS13 mutants. We performed expression studies and a sensitive recombinant VWF (rVWF) A1-A2-A3 cleavage test (detection limit, 0.78% of normal ADAMTS13 activity). A higher risk of acute renal impairment during bouts was observed in patients with childhood (<18 years) onset (odds ratio [OR], 24.6 [95% confidence interval (CI), 1.11 to 542.44]) or a relapsing (≥1 episode per year) disease (OR, 54.6 [95% CI, 2.25 to 1326.28...

Deficiency of ADAMTS13 Causes Thrombotic Thrombocytopenic Purpura

2010

Abstract—In the circulation, a plasma metalloprotease, ADAMTS13, cleaves von Willebrand factor (vWF) in a shear-dependent manner. This article reviews the role of this cleavage in regulating vWF-platelet interaction and proposes a scheme,for understanding how a deficiency of ADAMTS13 results in the development,of microthrombi,in patients with thrombotic thrombocytopenic,purpura. (Arterioscler Thromb Vasc Biol. 2003;23:388-396.) Key Words: von Willebrand factor,thrombotic thrombocytopenic,purpura,ADAMTS13 shear stress

Pathophysiology of thrombotic thrombocytopenic purpura

International Journal of Hematology, 2010

Thrombotic thrombocytopenic purpura (TTP) is a disorder with characteristic von Willebrand factor (VWF)-rich microthrombi affecting the arterioles and capillaries of multiple organs. The disorder frequently leads to early death unless the patients are treated with plasma exchange or infusion. Studies in the last decade have provided ample evidence to support that TTP is caused by deficiency of a plasma metalloprotease, ADAMTS13. When exposed to high shear stress in the microcirculation, VWF and platelets are prone to form aggregates. This propensity of VWF and platelet to form microvascular thrombosis is mitigated by ADAMTS13, which cleaves VWF before it is activated by shear stress to cause platelet aggregation in the circulation. Deficiency of ADAMTS13, due to autoimmune inhibitors in patients with acquired TTP and mutations of the ADAMTS13 gene in hereditary cases, leads to VWF-platelet aggregation and microvascular thrombosis of TTP. In this review, we discuss the current knowledge on the pathogenesis, diagnosis and management of TTP, address the ongoing controversies, and indicate the directions of future investigations.