Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein C (PC) is the central component of a major antithrombotic regulatory system with both anticoagulant and profibrinolytic properties. A deficiency of PC is one of several hereditary abnormalities of haemostatic proteins that have been described in patients with a propensity for thromboembolic complications. Major morbidity is often seen in these patients. The various aspects of hereditary PC deficiency in terms of clinical presentation, genetics, diagnosis and treatment of both homozygous and heterozygous states will be presented. In heterozygous deficiency, the levels of plasma PC are usually between 35% and 65% of normal, whereas the majority of normal individuals have levels between 70% and 130%. PC-deficient patients usually develop venous thrombotic complications between the ages of 15 and 40 years with a high incidence of DVT and pulmonary embolism. The majority of thrombotic lesions appear to develop spontaneously; others are associated with trauma, surgery or pregnancy. Treatment of symptomatic patients is initial heparin therapy followed by coumadin. After multiple thrombotic events, lifelong oral anticoagulant therapy is necessary. The potential complications of treatment are coumadin-induced skin necrosis, heparin-induced thrombocytopenia and bleeding. Homozygous PC deficiency, a rare but fatal hereditary condition, manifests itself with massive DIC and purpura fulminans in the newborn period. Effective treatment for these infants can be instituted with either oral anticoagulant therapy or PC replacement. The heterozygous deficiency of PC is similar to that found in other inherited disorders in that several genetic mechanisms are responsible for the expression of the disease. Both quantitative and qualitative decreases in PC exist, the former being type I deficiency and the latter, type II. The best initial diagnosis of either form involves a clotting (functional) assay while differentiation between the two also requires an antigenic (immunological) assay. Autosomal inheritance with significant variable penetrance is found with profound clinical implications. In summary, PC deficiency is one of a group of inherited disorders termed hereditary thrombotic disease, which may have serious implications for patient morbidity and mortality.
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PMID:Hereditary protein C deficiency: a review of the genetics, clinical presentation, diagnosis and treatment. 210 16

Thrombomodulin (TM) is a 557-amino acid protein with a broad cell and tissue distribution consistent with its wide-ranging physiological roles. When expressed on the lumenal surface of vascular endothelial cells in both large vessels and capillaries, its primary function is to mediate endothelial thromboresistance. The complete integral membrane-bound protein form displays five distinct functional domains, although shorter soluble (functional) variants comprising the extracellular domains have also been reported in fluids such as serum and urine. TM-mediated binding of thrombin is known to enhance the specificity of the latter serine protease toward both protein C and thrombin activatable fibrinolysis inhibitor (TAFI), increasing their proteolytic activation rate by almost three orders of magnitude with concomitant anticoagulant, antifibrinolytic, and anti-inflammatory benefits to the vascular wall. Recent years have seen an abundance of research into the cellular mechanisms governing endothelial TM production, processing, and regulation (including flow-mediated mechanoregulation)--from transcriptional and posttranscriptional (miRNA) regulation of TM gene expression, to posttranslational processing and release of the expressed protein--facilitating greater exploitation of its therapeutic potential. The goal of the present paper is to comprehensively review the endothelial/TM system from these regulatory perspectives and draw some fresh conclusions. This paper will conclude with a timely examination of the current status of TM's growing therapeutic appeal, from novel strategies to improve the clinical efficacy of recombinant TM analogs for resolution of vascular disorders such as disseminated intravascular coagulation (DIC), to an examination of the complex pleiotropic relationship between statin treatment and TM expression.
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PMID:Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects. 2360 13