Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In neonates and infants numerous clinical and environmental conditions such as the use of central lines, cardiac diseases and polycythemia, renal diseases such as congenital nephrotic syndrome and neonatal hemolytic uremic syndrome, peripartal asphyxia, infants of diabetic mothers, dehydration, septicemia, necrotizing enterocolitis, acute respiratory distress syndrome, and extracorporeal membrane oxygenation lead to elevated thrombin generation and subsequent thrombus formation. Genetic prothrombotic defects [protein C, protein S and antithrombin deficiency, mutations of coagulation factor V and factor II, elevated lipoprotein (a)] have been established as risk factors for thromboembolic events. The interpretation of laboratory results relies on age-dependent normal reference values. Because appropriate clinical trials are missing in these age groups, treatment recommendations are adapted from small-scale studies in neonates and infants and from guidelines relating to adult patient protocols. Secondary long-term anticoagulation should be administered on an individual basis.
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PMID:Neonatal thromboembolism. 1270 27

Historically, lethal exsanguinations and severe infections have been two major causes of maternal death. Gene mutations that lower the risk of profuse hemorrhage or severe infections would give a survival advantage. A single mutation of coagulation factor V, known as FV Leiden (FVL), can be such a beneficial mutation. FVL is common among Caucasians and today confers an increased risk of thromboembolism. However, the high prevalence of FVL (up to 15%) in the general population suggests that it has given an evolutionary advantage. In this review, we discuss possible mechanisms of the evolutionary survival advantage associated with FVL. In women, FVL confers lower risk of blood loss and profuse hemorrhage in association with delivery and improves the hemoglobin status. In addition, FVL carriers possibly have a survival advantage during sepsis. In conclusion, the high prevalence of FVL may be the result of one or more evolutionary selection advantages.
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PMID:Carriership of Factor V Leiden and evolutionary selection advantage. 1853 29

Derangement of the blood clotting system contributes strongly to multiple organ failure in severe sepsis. In this review, we examine two microbial modulators of the clotting system: polyphosphates and omptins. Polyphosphates are linear polymers of inorganic phosphate that are abundant in the acidocalcisomes of prokaryotes and unicellular organisms as well as in the dense granules of human platelets. Polyphosphates modulate haemostasis by: (1) triggering clotting via the contact pathway; (2) accelerating the activation of coagulation factor V (a key cofactor in blood clotting) and (3) causing fibrin to form clots whose fibrils are thicker and more resistant to fibrinolysis. While polyphosphates are found in all prokaryotes, omptins have a more limited distribution among certain Gram-negative species. Omptins are outer membrane aspartyl proteases which were recently found to proteolytically inactivate tissue factor pathway inhibitor (TFPI), the main inhibitor of the initiation phase of blood clotting. Omptin activity against TFPI requires lipopolysaccharide without O-antigen (rough LPS) such as is found on the surface of Yersinia pestis, the etiologic agent of plague. Interestingly, expression of Pla, the Yersinia pestis omptin, has a demonstrated virulence role in converting plasminogen into the fibrinolytic enzyme plasmin, which would seemingly antagonize any procoagulant effect of TFPI inactivation. However, since the rate of TFPI inactivation is much higher than the rate of plasminogen activation, we suggest that Pla may have a dual function in supporting the bubonic form of plague which is unique to Yersinia pestis.
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PMID:Polyphosphate and omptins: novel bacterial procoagulant agents. 1972 23

The inflammation-induced activation of the protein C pathway provides negative feedback inhibition of coagulation and exerts coagulation-independent anti-inflammatory and cytoprotective effects. The balance between these activities of aPC modulates the outcome of diverse inflammatory diseases such as encephalitis, diabetes, and sepsis; and is affected by naturally occurring aPC-resistance of coagulation factor V Leiden.
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PMID:Inflammation-associated activation of coagulation and immune regulation by the protein C pathway. 2475 38