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)

Purpura fulminans is associated with homozygous protein C and homozygous protein S deficiency or may follow bacterial or viral infections. We present 2 children from 2 unrelated Arab families with purpura fulminans who were double heterozygotes for factor V Leiden inherited from their fathers and protein S deficiency inherited from their mothers. No previous thrombotic events have occurred in either patient or their respective family members. In one patient sepsis accompanied by disseminated intravascular coagulation appeared to be the trigger of purpura fulminans. In the other patient varicella infection preceded purpura fulminans and was also associated with disseminated intravascular coagulation. This report emphasizes the need for evaluation of hereditary defects in the inhibitory mechanisms of blood coagulation in patients with purpura fulminans at any age.
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PMID:Purpura fulminans induced by disseminated intravascular coagulation following infection in 2 unrelated children with double heterozygosity for factor V Leiden and protein S deficiency. 924 37

With the success of pediatric live donor liver transplantation (LDLT) and the continued shortage of cadaveric donors, adult-to-adult LDLT has been performed at some centers, including ours. We performed a detailed histologic review of all liver specimens obtained from 9 adult recipients at and after LDLT and correlated these findings with the patients' course and outcome. Five patients had histologic evidence of biliary tract pathology; 3 of 5 required surgical or radiologic intervention. The other 2 had clinically insignificant biliary disease. Diffuse hepatocytic hemorrhagic necrosis secondary to massive portal blood flow after portal venous revascularization resulted in graft failure and retransplantation in a single patient with severe preoperative portal hypertension. Two perioperative deaths were caused by sepsis and multiorgan failure (day 25) and generalized thrombosis related to factor V Leiden (day 6). The preoperative diagnosis, presence of portal vein thrombosis in the native liver, postoperative cholangiopathy, and subcapsular hemorrhagic necrosis in donor liver wedge biopsies did not affect the short-term outcome. In conclusion, biliary tract pathology is common after adult-to-adult LDLT but does not negatively affect graft or patient survival. Infrequent but catastrophic vascular complications related to portal hemodynamics or thrombosis can result in graft loss and/or patient death.
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PMID:Adult-to-adult live donor liver transplantation: a short-term clinicopathologic study. 1152 Dec 25

Sepsis is associated with systemic inflammation, coagulopathy, and disrupted protein C (PC) pathway function. The effect of prothrombotic polymorphism, factor V Leiden (Arg506Gln; FV Leiden), was examined in a large clinical trial (PROWESS) of severe sepsis and a mouse endotoxemia model. In PROWESS, 4.1% (n = 65) of patients were heterozygous FV Leiden (VL+/-) carriers. The 28-day mortality was lower in VL+/- (13.9%) than in non-FV Leiden (VL-/-; 27.9%) patients (P =.013). The mortality benefit of recombinant human activated PC (rhAPC) treatment was similar in VL+/- (placebo, 15.6%; rhAPC,12.1%) and VL-/- patients (placebo, 31.0%; rhAPC, 24.7%; interaction P =.981). VL+/- status did not appear to influence baseline biomarkers of coagulopathy and inflammation or disease severity, with the exception that vasopressor usage was less in VL+/- patients (46.2% versus 63.0%; P =.009). In a median lethal dose (40 mg/kg) endotoxin mouse model, VL+/- mice had lower mortality than wild-type mice (19% versus 57%; P =.008), whereas the mortality of homozygous (VL+/+) mice was almost identical to that of wild-type mice (65% versus 57%; P =.76). The findings suggest that FV Leiden constitutes a rare example of a balanced gene polymorphism that maintains the FV Leiden mutation in the general gene pool due to a survival advantage of VL+/- in severe sepsis.
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PMID:Survival advantage associated with heterozygous factor V Leiden mutation in patients with severe sepsis and in mouse endotoxemia. 1286 95

Thrombosis of the internal jugular vein is a rare event but one that can have serious consequences. Most cases reported in the literature have occurred in patients with indwelling central venous catheters, in association with head and neck sepsis, or in hypercoagulable states. However, a small number of cases have been associated with in vitro fertilization and more often with the ovarian hyperstimulation syndrome (OHSS). We report the case of a 30-year-old woman heterozygous for both the prothrombin 3' UTR mutation and for the factor V Leiden mutation who presented with a proximal deep vein thrombosis following in vitro fertilization. She subsequently developed an internal jugular vein thrombosis extending into the subclavian and axillary vein despite therapeutic anticoagulation with a low molecular weight heparin. Thromboembolic events can occur in the absence of other clinical features of OHSS, especially in patients with underlying prothrombotic abnormalities. Neck pain and swelling in a pregnant woman, especially one that has undergone in vitro fertilization, should be taken seriously and investigated with duplex scanning and/or MRI. Women with a personal or family history of thrombosis undergoing in vitro fertilization should be made fully aware of the potential thrombotic risks and should be considered for a thrombophilia screen.
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PMID:Deep vein thrombosis followed by internal jugular vein thrombosis as a complication of in vitro fertilization in a woman heterozygous for the prothrombin 3' UTR and factor V Leiden mutations. 1287 33

We report the case of a 18-year-old woman with portal vein thrombosis and chronic hepatitis C virus. Portal vein thrombosis was diagnosed by chance on ultrasound examination during initial hepatitis C virus-positive patient screening. The patient interview revealed a history including exchange transfusion at birth, followed by necrotising ulcerocolitis and septicemia. The investigation of general factors favoring thrombosis showed acquired protein S deficiency and heterozygous factor V Leiden mutation. This case demonstrates the value of systematic investigations for general thrombophilic factors in cases of portal vein thrombosis even when a local cause is found.
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PMID:[Portal vein thrombosis associated with factor V Leiden mutation in a woman who underwent exchange transfusion at birth]. 1291 Feb 30

Cerebral infarcts are an important cause of neonatal convulsions. We report the etiologic factors, and clinical and neuroradiologic findings of four full term neonates who presented with neonatal convulsions and had cerebral infarct. In our patients the risk factors for the cerebral infarct were perinatal asphyxia, sepsis, dehydration and catheter application. All had convulsions as the initial sign of infarct and had cranial imaging which revealed the definitive diagnosis. The patients underwent an extensive evaluation for hereditary causes of cerebral infarct that included anticoagulant factors (Proteins C and S, antithrombin III, antiphospholipid antibodies), factor V Leiden and prothrombin gene mutations, blood and urine amino acid and urine organic acid levels. The results were found to be within normal limits. In conclusion, neonatal convulsions can be the first sign of cerebral infarct. For this reason it seems preferable to include cranial imaging by computed tomography or magnetic resonance imaging (MRI) in the work-up of cases with unexplained neonatal convulsions.
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PMID:Cerebral infarcts in full term neonates. 1292 2

Individuals vary considerably in their susceptibility to infection and in their ability to recover from apparently similar infectious processes. These differences can be partially explained by polymorphisms of the genes encoding proteins involved in mediating and controlling the innate immune response, the inflammatory cascade, coagulation, and fibrinolysis. It is evident from experimental studies that dysregulation of the coagulation system, which is characteristic of the pathophysiology of septic shock (a procoagulant and antifibrinolytic state), contributes to systemic inflammation and death in sepsis. Several genetic variations in proteins that increase coagulation or impair anticoagulation and fibrinolysis have been described. Thus, polymorphisms have been reported in prothrombin, fibrinogen, factor V, tissue factor, endothelial protein C receptor, and plasminogen activator inhibitor-1 genes. Some of them are associated with an increased risk of pulmonary emboli, acute myocardial infarction, stroke, and severe sepsis. Hence, the deletion polymorphism (4G) within the promoter region of the plasminogen activator inhibitor-1 gene leads to impaired fibrinolysis and influences the severity and outcome of meningococcal disease and the susceptibility to severe sepsis and multiple organ failure after trauma. The factor V Leiden mutation is associated with thrombotic events and has been reported to exacerbate purpura fulminans in meningococcal infection. Surprisingly, this genetic variant seems to provide a survival advantage in severe sepsis, underlying the extreme complexity of the interaction between inflammation and coagulation. The study of genetic polymorphisms might provide important insights into the pathogenesis of severe sepsis and could make it possible to identify individuals who are at risk of developing or dying of severe infections. As genetic associations are discovered, medical practice can become more preemptive, using the predictive ability of genetics to anticipate disease and recommend therapy.
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PMID:Importance of hemostatic gene polymorphisms for susceptibility to and outcome of severe sepsis. 1511 37

No identifiable cause can be found in more than half of the cases of portal vein thrombosis (PVT). Our aim was to assess the prevalence of factor V Leiden mutation and other thrombophilic factors as risk factors in the development of PVT in the pediatric age group. From March 2001 to January 2002, 40 children with PVT were enrolled in the study, in addition to 20 age-matched and sex-matched controls. Protein C, protein S, antithrombin III, and activated protein C resistance (APCR) were assayed. Molecular study of factor II and factor V mutations was carried out. Of the patients, 25 had detectable hereditary thrombophilia (62.5%), 12 had factor V Leiden mutation (30%), 11 had protein C deficiency (27.5%), 6 had factor II mutation (15%), 1 had antithrombin III deficiency (2.5%), and none had protein S deficiency. Five children had concurrence of more than one defect. Factor V Leiden mutation is the most common hereditary thrombophilia associated with PVT and the relative risk of factor V Leiden mutation, as a cause of PVT, was six times more than in controls (odds ratio=6). Concurrence of more than one hereditary thrombophilic factor was seen in 12.5% of our patients. Circumstantial risk factors (neonatal sepsis, umbilical sepsis, umbilical catheterization) were not more significantly prevalent among patients with hereditary thrombophilia than among those with no detectable abnormalities in anticoagulation.
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PMID:Prevalence of factor V Leiden mutation and other hereditary thrombophilic factors in Egyptian children with portal vein thrombosis: results of a single-center case-control study. 1530 26

The protein C pathway is a major regulator of blood coagulation, since it controls the conversion of prothrombin to thrombin through a feedback inhibition mechanism. Protein C circulates in plasma as an inactive zymogen and is activated on the surface of endothelial cells by the thrombin-thrombomodulin complex, a process that can be further enhanced when protein C binds to its membrane receptor, the endothelial-cell protein C receptor. Activated protein C (APC) is then released from the complex, binds protein S and inhibits thrombin formation by inactivating coagulation factors Va and VIIIa. The importance of the protein C anticoagulant pathway is emphasized by the increased risk of venous thromboembolism (VTE) associated with protein C and protein S deficiencies, the factor V Leiden mutation, and reduced circulating APC levels. The protein C pathway also plays a significant role in inflammatory processes, since it prevents the lethal effects of E. coli-associated sepsis in animal models and improves the outcome of patients with severe sepsis. APC seems to display anti-apoptotic and neuroprotective activities. Thus, it reduces organ damage in animal models of sepsis, ischemic injury, endothelial cell injury, or stroke. Further research will hopefully widen the current therapeutic perspectives in all these illnesses, where these effects might play a crucial role in their treatment. This review will summarize the mechanisms that contribute to these biological activities of the protein C pathway.
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PMID:The multifunctional protein C system. 1585 99

Several genetic polymorphisms have been identified in patients with sepsis and severe sepsis, such as the tumor necrosis factor-alpha (TNF-alpha) and TNF-beta genes, the interleukin-1 (IL-1) family, the IL-6, the IL-10, the CD-14, the Toll-like receptors, plasminogen activator inhibitor type 1, and the factor V 1691G-A mutations. In this study, the relationship between the TNF-alpha 308G/A, the IL-6-174 G/C, the PAI-1, the FVL, the EPCR, and the Cathepsin G (Ars 125 Ser) polymorphisms and the development and outcome of sepsis in pediatric patients was studied. TNF-alpha 308 G/A, PAI-1 4G/4G, and EPCR mutations influence the risk of severe sepsis in children. IL-6 174 G/C, FVL, and Cathepsin G (Ars 125 Ser) did not influence the incidence and mortality of severe sepsis.
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PMID:Effect of various genetic polymorphisms on the incidence and outcome of severe sepsis. 1644 34


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