Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deep hypothermic cardiopulmonary bypass with or without circulatory arrest has been used to facilitate the surgical repair of complex cerebrovascular lesions. The advantages of deep hypothermia have been tempered by the occurrence of coagulopathy that is associated with substantial morbidity and mortality. This study analyzed retrospectively the records of 13 patients who underwent cerebrovascular neurosurgery using deep hypothermic cardiopulmonary bypass with or without circulatory arrest during the period 1993 through 1999. All patients received the serine protease inhibitor aprotinin in an effort to avoid the development of a coagulopathy, defined as hemorrhage requiring reoperation. No patients developed postoperative intracranial hemorrhage. There was also no evidence of renal dysfunction, deep venous thrombosis, myocardial infarction, or pulmonary embolism. In conclusion, this study suggests that aprotinin may be beneficial to avoid the coagulopathy that is more likely to occur if deep hypothermic cardiopulmonary bypass with or without circulatory arrest is used for craniotomy without adverse effects on renal function or apparent thrombotic complications.
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PMID:Aprotinin and deep hypothermic cardiopulmonary bypass with or without circulatory arrest for craniotomy. 1190 94

Antithrombin (AT) deficiency is an autosomal dominant disorder, and identification of mutation AT variants would improve our understanding of the anticoagulant function of this serine protease inhibitor (SERPIN) and the molecular pathways underlying this disorder. In the present study, we performed whole-exome sequencing of a Chinese family with deep vein thrombosis, and identified a new small deletion that eliminates four amino acids (INEL) from exon 4 of SERPINC1 gene. This causes type I AT deficiency by enhancing the intracellular retention of this protein. AT retention leads to endoplasmic reticulum (ER) stress, which further inhibits AT release. In addition, ER stress activates ER-associated degradation, which promotes AT degradation. Suppression of ER stress enhanced the secretion of AT, while inhibition of ER-associated degradation suppressed AT release. Thus, our study identified a new mutation (INEL deletion) causing type I AT deficiency, and uncovered a novel mechanism for AT retention through enhanced ER stress, which may provide an innovative approach for treating AT deficiency.
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PMID:A small deletion in SERPINC1 causes type I antithrombin deficiency by promoting endoplasmic reticulum stress. 2770 19

Fondaparinux is a synthetic heparin pentasaccharide with a sequence identical to that found in anticoagulant heparin. It is a pure compound with a molecular weight of 1728Da. Fondaparinux catalyzes the conformational change of a serpin or serine protease inhibitor antithrombin III to accelerate the suicidal inactivation of factor Xa over 340-fold, which in turn inhibits thrombin generation in the coagulating signal transduction pathway. Fondaparinux does not inhibit thrombin activity, release tissue factor pathway inhibitor, or possess other properties of heparin such as anti-inflammatory, anti-viral, anti-angiogenesis, anti-neoplastic, and anti-metastatic effects though high affinity interactions with a variety of proteases, protease inhibitors, chemokines, cytokines, growth factors, and their respective receptors. Low antithrombin III levels in blood circulation also affects the efficacy of Fondaparinux. Thus, Fondaparinux represents a refined use of the anti-factor Xa property of heparin. As an anti-factor Xa drug, Fondaparinux has complete bioavailability subcutaneously, instant onset of action, a half-life of 15-20h, and a direct renal excretion without any metabolism. Fondaparinux has been shown to be superior to low molecular weight heparin in preventing deep vein thrombosis. Clinically, Fondaparinux is used for the prevention of deep vein thrombosis in patients who have had orthopedic surgery as well as for the treatment of deep vein thrombosis and pulmonary embolism with limitations of use in elderly, low weight, renal impaired patients and in those receiving spinal anesthesia. Clinical studies showed that Fondaparinux acts in prevention and treatment of venous thromboembolism and in ischemic heart disease without significant risk of bleeding.
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PMID:The clinical use of Fondaparinux: A synthetic heparin pentasaccharide. 3103 Jul 56