Chapter 109. Disorders of Platelets and Vessel Wall (Part 7)

Thrombotic Thrombocytopenic Purpura TTP and HUS were previously considered overlap syndromes. However, in the past few years the pathophysiology of inherited and idiopathic TTP has become better understood and clearly differs from HUS. TTP was first described in 1924 by Eli Moschcowitz and characterized by a pentad of findings that include microangiopathic hemolytic anemia, thrombocytopenia, renal failure, neurologic findings, and fever. The full-blown syndrome is less commonly seen now, probably due to earlier diagnosis. The introduction of treatment with plasma exchange markedly improved the prognosis in patients, with a decrease in mortality from 85–100% to 10–30%. The pathogenesis of inherited. | Chapter 109. Disorders of Platelets and Vessel Wall Part 7 Thrombotic Thrombocytopenic Purpura TTP and HUS were previously considered overlap syndromes. However in the past few years the pathophysiology of inherited and idiopathic TTP has become better understood and clearly differs from HUS. TTP was first described in 1924 by Eli Moschcowitz and characterized by a pentad of findings that include microangiopathic hemolytic anemia thrombocytopenia renal failure neurologic findings and fever. The full-blown syndrome is less commonly seen now probably due to earlier diagnosis. The introduction of treatment with plasma exchange markedly improved the prognosis in patients with a decrease in mortality from 85-100 to 10-30 . The pathogenesis of inherited Upshaw-Schulman syndrome and idiopathic TTP is related to a deficiency of or antibodies to a metalloprotease that cleaves vWF and ADAMTS13 respectively. vWF is normally secreted as ultralarge multimers which are then cleaved by ADAMTS13. The persistence of ultralarge vWF molecules are thought to contribute to pathogenic platelet adhesion and aggregation Fig. 109-4 . This defect alone however is not sufficient to result in TTP as individuals with a congenital absence of ADAMTS13 develop TTP only episodically. Additional provocative factors have not been defined. The level of ADAMTS13 activity as well as antibodies can now be detected by laboratory assays. However assays with sufficient sensitivity and specificity to direct clinical management have yet to be defined. Figure 109-4 Pathogenesis of thrombotic thrombocytopenic purpura TTP . Normally the ultra-high molecular-weight multimers of von Willebrand factor vWF produced by the endothelial cells are processed into smaller multimers by a plasma metalloproteinase called ADAMTS13. In TTP the activity of the protease is inhibited and the ultra-high molecular-weight multimers of vWF initiate platelet aggregation and thrombosis. From Vesely et al. Copyright American Society of

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