Thrombotic Microangiopathies: Towards a Pathophysiology-Based Classification

Author(s): Paul Coppo, Agnes Veyradier

Journal Name: Cardiovascular & Hematological Disorders-Drug Targets
Formerly Current Drug Targets - Cardiovascular & Hematological Disorders

Volume 9 , Issue 1 , 2009

Become EABM
Become Reviewer
Call for Editor


Thrombotic microangiopathies (TMA) encompass various diseases characterized by a microangiopathic hemolytic anemia, platelet clumping, and organ failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) is a particularly severe form of TMA characterized by systemic organ failure which results from a severe defect in ADAMTS13, a plasma enzyme specifically involved in the cleavage of highly hemostatic unusually large (UL) von Willebrand factor (VWF) multimers into smaller and less adhesive VWF forms. Failure to degrade these UL-VWF multimers leads to excessive platelet aggregates and capillary occlusion. ADAMTS13 deficiency results from bi-allelic mutations in hereditary TTP, whereas in acquired forms it results from autoantibodies that alter the protein function. Patients with acquired idiopathic TTP have a trend to develop autoimmunity, since a clinical context of autoimmunity may be found in 30 p. cent of cases. Moreover, the remarkable efficiency of monoclonal antibodies directed against CD20 antigen of B lymphocytes in refractory or chronic relapsing forms provides an additional indirect argument to consider acquired TTP as an autoimmune disease. Hemolytic uremic syndrome (HUS) is characterized prominently by a renal failure. In most cases, HUS is caused by entero- hemorrhagic Escherichia coli (diarrhea-positive HUS). Diarrhea-negative HUS, termed atypical HUS, was associated with a dysfunction in complement pathway involving mutations in factor H, factor I, CD46/MCP, factor B and C3 components. The major improvement in our understanding of TMA pathophysiology allows now a more accurate molecular classification of TMA syndromes, which opens fascinating perspectives of targeted therapies in the forthcoming years.

Keywords: Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, thrombotic microangiopathies, thrombocytopenia, ADAMTS13, autoimmune disease, complement

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2009
Page: [36 - 50]
Pages: 15
DOI: 10.2174/187152909787581318

Article Metrics

PDF: 69