Cardiovascular & hematological disorders drug targets
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Cardiovasc Hematol Disord Drug Targets · Mar 2009
ReviewThrombotic microangiopathies: towards a pathophysiology-based classification.
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. ⋯ 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.