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TTP/HUS BY Sahar Jasim M. Supervisor DR. Sadiq Khalf TMA definition ✓ Thrombotic microangiopathies (TMAs) are a group of heterogeneous disorders, ✓ characterized by disseminated thrombus formation in arterioles and capillaries with endothelial swelling or damage ✓ resulting in thrombocytopenia,...

TTP/HUS BY Sahar Jasim M. Supervisor DR. Sadiq Khalf TMA definition ✓ Thrombotic microangiopathies (TMAs) are a group of heterogeneous disorders, ✓ characterized by disseminated thrombus formation in arterioles and capillaries with endothelial swelling or damage ✓ resulting in thrombocytopenia, microangiopathic hemolytic anemia (MAHA), and potential end organ injury.  MAHA was initially described to result from intravascular coagulation that leads to mechanical destruction of red blood cells (i.e. anemia and fragmentation of red blood cells) as they traverse through platelet and/or fibrin-rich thrombi  ADAMTS13 ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). The ADAMTS13 gene consists of 29 exons at chromosome location 9q34.2. It synthetized in the liver (hepatic stellate cells) and vascular endothelial cells ADAMTS13 consists of a multi- domain structure with the N-terminal domains (MDTCS) responsible for proteolysis through a series of exosites for VWF binding and cleavage, whilst the C-terminal domains regulate protein latency.  The physiological function of this protease, present in plasma and platelets, is to regulate the size of VWF by disposing of ultra large multimers as soon as they are secreted from endothelial cells into plasma by cleaving the Tyr1605-Met1606 bond in the von Willebrand factor A2 domain.thereby preventing heightened platelet aggregation and thrombus formation The circulating form of ADAMTS13 is the closed form while open form of ADAMTS13 found in acute TTP Thrombotic Thrombocytopenic Purpura TTP is a rare form of (TMA), characterized by microangiopathic hemolytic anemia (MAHA), severe thrombocytopenia, and ischemic end-organ damage resulting from formation of platelet-rich thrombi in the microvasculature. Incidence