Thrombotic Thrombocytopenic Purpura and the Hemolytic Uremic Syndrome
| Autor: | P.M. Carey |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
biology
business.industry Thrombotic thrombocytopenic purpura Globotriaosylceramide medicine.disease ADAMTS13 Schistocyte Complement system chemistry.chemical_compound chemistry Von Willebrand factor hemic and lymphatic diseases Atypical hemolytic uremic syndrome Immunology medicine Alternative complement pathway biology.protein business |
| Zdroj: | Pathobiology of Human Disease ISBN: 9780123864574 |
| Popis: | Thrombotic microangiopathies have often been grouped together as the same entity with a different clinical presentation. This article serves to present current information on the understanding of the pathobiology of thrombotic thrombocytopenic purpura (TTP), diarrhea-associated hemolytic uremic syndrome (HUS), and atypical HUS (aHUS). The latter are now characterized as separate clinical entities with a distinct pathogenesis. TTP pathology derives from alteration in the normal interaction between von Willebrand factor (vWF) and ADAMTS13 cleaving protease, which changes vWF into smaller multimers. Absence of ADAMTS13 as a hereditary or acquired deficit results in increased numbers of large multimers of vWF. These large vWF multimers promote spontaneous platelet aggregation, development of microvascular thrombi, and associated end organ damage. HUS was once characterized as a type of TTP. Ninety percent of cases are due to the complications of infection with an organism prone to produce an endotoxin, most commonly a Shiga toxin, during an infection with enterohemorrhagic Escherichia coli . The Shiga toxins can generate cell death and marked inflammation primarily in the kidney, but may also affect the brain and other globotriaosylceramide rich cells. Secondary generation of microvascular thrombi in the damaged organs can result in chronic disease after resolution of the infection. aHUS accounts for ~ 10% of HUS cases. This is a classic disease of complement dysregulation. Mutations to regulatory proteins or active proteins in the alternative complement pathway lead to overactivation of the alternative complement pathway, with the associated inflammation, cell death, and microvascular thrombi affecting primarily the kidney. |
| Databáze: | OpenAIRE |
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