Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activated protein C (APC) resistance, defined as a low APC ratio, is associated with the factor V mutation R506Q (factor V Leiden). APC ratio may also be influenced by other clinical and coagulation variables, which we studied in 460 men and 495 women aged 25-74 years, from a random population sample (Glasgow MONICA Survey). APC ratio correlated positively with APTT; and inversely with factor VIIIc, factor IXc, antithrombin activity, prothrombin F1+2 fragment, and thrombin-antithrombin complexes; but not with other coagulation variables. APC ratio decreased with age, but APTT did not. APC ratio and APTT were significantly lower in women versus men, and were significantly lower in users of oral contraceptives or hormone replacement therapy. The FV:R506Q mutation (prevalence 2.5%) was associated with lower APC ratio and protein C and S activities and with higher factor VIIIc levels; but not with increases in F1+2 fragment or thrombin-antithrombin complexes. APC ratio correlated inversely with total cholesterol and diastolic blood pressure; and in women with triglycerides, systolic blood pressure, and body mass index. Obesity was associated with a significantly lower APC ratio. In contrast, smoking markers correlated positively with APC ratio in men. These associations of APC ratio may be relevant to the increased risks of venous thrombosis with age, female sex, oestrogen use, obesity and high factor VIIIc levels. The association of APC resistance with elevated plasma levels of coagulation markers suggests that this phenotype represents an in vivo hypercoagulable state.
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PMID:Activated protein C resistance and the FV:R506Q mutation in a random population sample--associations with cardiovascular risk factors and coagulation variables. 1040 68

The identified main causes of inherited thrombophilia are deficiencies of antithrombin, protein C and protein S, activated protein C (APC) resistance and the factor V Leiden mutation, mutant factor II, and inherited hyperhomocysteinemia. In women from symptomatic families these defects may be associated with an increased risk of venous thrombosis in pregnancy and recurrent fetal loss. Inherited thrombophilia is common and appears to be a multigene disorder. The thrombotic risk would seem to be greatest in women with antithrombin deficiency and more than one thrombophilia defect. The abnormalities that are now recognized represent only part of the genetic predisposition to thrombosis. In assessing thrombotic risk in pregnancy, acquired risk factors as well as genetic predisposition should be considered. Increasing age, obesity, immobility, and delivery by cesarean section are major risk factors. Pregnancy should be planned, and each patient should be managed on an individual basis. In pregnancy, heparin is the anticoagulant of choice, and as far as possible, treatment with warfarin should be avoided because of the risks to the fetus. When patients are on long-term treatment with warfarin, pregnancy should be avoided, and warfarin should be discontinued prior to embarking on a pregnancy or as soon as pregnancy is suspected and before 6 weeks' gestation. In women from symptomatic families with antithrombin deficiency, adjusted dose heparin throughout pregnancy is recommended and warfarin for at least 3 months post partum. In protein C and protein S deficiency, factor V Leiden, or mutant factor II, treatment can be based on personal and family history. Thromboprophylaxis in late pregnancy and post partum should be considered. Fetal loss may be increased in women with inherited thrombophilia. The risk appears greatest in women with antithrombin deficiency and women with more than one thrombophilia defect. A number of reports have claimed that prophylactic treatment with heparin during pregnancy has resulted in successful pregnancy in women with recurrent fetal death and inherited thrombophilia.
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PMID:Perinatal aspects of inherited thrombophilia. 1062 6

Venous Thromboembolism develops as the result of multiple interactions between non-genetic and genetic risk factors. The most important non-genetic risk factors are age, tissue damage, oral contraception, pregnancy, obesity and lack of physical activity. Inborn factors predisposing to thrombosis are present in the majority of patients. These comprise defects affecting the anticoagulant pathways of blood coagulation like antithrombin III, protein C and protein S. Together these defects are found in 15-20% of thrombophilia families. The relatively rare defects of antithrombin III, protein C and protein S stand in contrast to two common genetic polymorphisms of procoagulant molecules, factor V-Leiden, the most frequent cause for resistance to activated protein C, and the prothrombin 20210 A allele. Together, these anomalies are found in almost two third of the thrombophilia families. The identification of factor FV-Leiden and prothrombin 20210 A has allowed to examine in detail interactions between genetic and non-genetic risk factors of thromboembolism. The results of these studies indicate that many symptomatic individuals are endowed with more than one (genetic and/or environmental) risk factor. Thrombophilia thus represents an oligogenetic rather than monogenetic clinical phenotype, the expression of which is amplified by circumstantial risk factors. As a consequence of the "multiple hit" concept, the laboratory screening of thrombosis patients needs to include all of the known genetic risk factors even if the "clinical" situation seemingly provides sufficient "explanation" for a thrombotic event.
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PMID:The molecular mechanisms of inherited thrombophilia. 1095 82

From the information presented in this article, it can be concluded that clinical suspicion of VTE should be increased in patients with a history of VTE, recent surgery, spinal cord injury, trauma, or malignancy. A variety of medical illnesses also increase the risk of venous thrombosis, including congestive heart failure, myocardial infarction, stroke with paresis, nephrotic syndrome, cigarette smoking, and obesity. Hypercoagulable states, such as antithrombin III deficiency, protein C deficiency, protein S deficiency, or factor V Leiden mutation should be considered in those patients who develop VTE in the absence of known risk factors. Additionally, the presence of vena caval filters does not exclude the possibility of PE or recurrent DVT. With a careful assessment of risk, physicians can hope to increase the diagnostic yield of VTE and decrease the significant morbidity and mortality of caused by this disease.
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PMID:Epidemiology of venous thromboembolic disease. 1176 74

The aim of this study was to investigate prospectively the incidence of deep venous thrombosis (DVT) after surgery for morbid obesity. The series comprised 116 consecutive patients undergoing Roux-en-Y gastric bypass. The median age and body mass index were 35 years (range 19-59 years) and 42 kg/m2 (range 32-68 kg/m2), respectively. The patients were examined with duplex ultrasonography pre- and postoperatively. No patient had any symptoms or signs of DVT postoperatively, and ultrasonography showed no signs of thrombosis in iliac, femoral, and popliteal veins in any of the patients. Two patients (1.7%) had a thrombus in the peroneal vein of one leg. Repeated ultrasonographic investigation after 1 week showed complete resolution of both. One patient with a previously unknown activated protein C resistance had an angiographically confirmed minor pulmonary embolus. The incidence of venous thromboembolism after obesity surgery seems to be low, and obesity as a risk factor for thromboembolic disease might have been overestimated in the past.
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PMID:Incidence of deep venous thrombosis in patients undergoing obesity surgery. 1191 Apr 82

Calciphylaxis is a small vessel vasculopathy involving mural calcification with intimal proliferation, fibrosis, and thrombosis. This syndrome occurs predominantly in individuals with renal failure and results in ischemia and necrosis of skin, subcutaneous fat, visceral organs, and skeletal muscle. The syndrome causes significant morbidity in the form of infection, organ failure, and pain. Mortality rates are high. In individuals with renal failure, risk factors for the development of calciphylaxis include female sex, Caucasian race, obesity, and diabetes mellitus. Many cases occur within the first year of dialysis treatment. Several recent reports demonstrate that prolonged hyperphosphatemia and/or elevated calcium x phosphorus products are associated with the syndrome. Protein malnutrition increases the likelihood of calciphylaxis, as does warfarin use and hypercoagulable states, such as protein C and/or protein S deficiency. Recent advances in diagnostic tools and therapeutic strategies have helped in the management of patients with calciphylaxis.
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PMID:Calciphylaxis: emerging concepts in prevention, diagnosis, and treatment. 1210 Apr 55

Oral contraceptive therapy (OCT) is widely used in the world. It is usually safe and effective but side effects are occasionally seen. Venous thromboembolism is one of the most feared side effects. To avoid this complication adequate guidelines are needed. These have to take into account family history, personal history, and suitable laboratory investigations. The presence of an idiopathic venous thrombosis in the family or in the personal history is of paramount importance. However it is often difficult to ascertain whether a venous thrombosis is idiopathic or not. Even when there is doubt, a coagulation study should be carried out. An adequate coagulation study in this case should include at least an evaluation of antithrombin, protein C, and protein S. A search for homozygosity of factor V Leiden appears advisable. These defects represent absolute contraindications to the use of OCT. Relative contraindications may be represented by other minor coagulation disorders such as heterozygous factor V Leiden, fibrinolysis defects, and a G-to-A 20210 prothrombin abnormality. Other noncoagulation-related conditions such as hypertension, liver damage, and obesity may represent absolute or relative contraindications to the use of OCT.
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PMID:Tentative guidelines and practical suggestions to avoid venous thromboembolism during oral contraceptive therapy. 1212 Oct 63

Abnormalities in coagulation and haemostasis represent a well-known link between obesity and thrombosis (both arterial and venous). Several studies have shown that obese patients have higher plasma concentrations of all pro-thrombotic factors (fibrinogen, vonWillebrand factor (vWF), and factor VII), as compared to non-obese controls, with a positive association with central fat. Similarly, plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be higher in obese patients as compared to non-obese controls and to be directly correlated with visceral fat. Furthermore, obesity is characterized by higher plasma concentrations of anti-thrombotic factors, such as tissue-type plasminogen activator (t-PA) and protein C, as compared to non-obese controls, the increase in these factors being likely to represent a protective response partly counteracting the increase in pro-thrombotic factors. The issue of whether adipose tissue contributes directly to plasma PAI-1, its products stimulating other cells to produce PAI-1, or whether it primarily contributes indirectly has not yet been resolved. It has been proposed that the secretion of interleukin-6 (IL-6) by adipose tissue, combined with the actions of adipose tissue-expressed TNF-alpha in obesity, could underlie the association of insulin resistance with endothelial dysfunction, coagulopathy, and coronary heart disease. The role of leptin in impairing haemostasis and promoting thrombosis has been recently reported. Finally, some hormonal abnormalities (androgen, F, catecholamines) associated with the accumulation of body fat may contribute to the impairment of coagulative pathway in obesity. As to intervention strategies, dietary (i.e., low-fat high-fiber diet) and lifestyle (i.e., physical activity) measures have been demonstrated to be effective in improving the obesity-associated pro-thrombotic risk profile.
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PMID:Coagulation and fibrinolysis abnormalities in obesity. 1250 53

Frequently an inherited predisposition to thrombosis remains clinically silent until an additional environmental factor intervenes. The present study aimed to assess distribution of inherited risk factors of venous thrombosis in patients with venous thromboembolism (VTE). The prevalences of factor V Leiden (FV Leiden), prothrombin factor II G20210A (FII G20210A), C677T and A1298C of methylenetetrahydrofolate reductase (MTHFR) mutations were studied in 149 VTE patients and 100 controls. The following key risks were established: previous deep venous thrombosis or pulmonary embolism (23.5%), bed rest (34.2%), immobilisation of lower limb (10.1%), hospitalisation (30.9%) and obesity (28.9%). In 29 (19%) patients and in three (3%) controls FV Leiden was found. A significant association between VTE and FV Leiden was established. There were six (4%) carriers of the FII G20210A among VTE patients and one in the controls. No associations between VTE and MTHFR polymorphisms (C677T, A1298C) were found. In three of 149 patients both FV Leiden and FII G20210A polymorphisms were observed. The mean protein C activity was slightly, though nonsignificantly, smaller in VTE patients. In conclusion, there was a positive association between venous thromboembolism and factor V Leiden. Only a weak trend favouring a relationship between prothrombin factor II G20210A and venous thrombolism was present. No associations between common polymorphisms of methylenetetrahydrofolate reductase and venous thromboembolism were found.
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PMID:Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. 1257 Jan 4

It has been suggested that thrombotic tendency increases the risk of myocardial infarction (MI). To investigate the association between the risk of MI at a young age and genetic thrombogenic disorders (G20210A mutation in the prothrombin gene, G1691A mutation in the factor V gene and deficiencies of protein C, protein S and antithrombin III) we conducted a case-control study among 70 survivors of MI who had experienced the event before the age of 36 and 260 healthy subjects. The G20210A mutation in the prothrombin gene was found more often in young patients with MI than among controls (11.4 versus 3.1%). The odds ratio (OR) for MI for carriers versus non-carriers was 4 (95% confidence interval [CI], 1.5 to 11.3). The adjusted OR for major cardiovascular risk factors (smoking, hypecholesterolaemia, diabetes mellitus, hypertension and obesity) was 4.3 (95% CI, 1.3 to 14). The simultaneous presence of both G20210A mutation in the prothrombin gene and smoking further increased the risk of MI compared with nonsmokers and non-carriers (OR, 58; 95% CI, 11.4-294). The G1691A mutation in factor V gene was not associated with an increased relative risk for MI (OR, 0.87; 95% CI, 0.26 to 2.5). Finally, there was no significant difference in the prevalence of deficiencies of protein C, protein S and antithrombin III between cases and controls. In conclusion, our data indicate that the G20210A mutation in the prothrombin gene was the only genetic prothrombotic risk factor associated with the risk of developing MI under the age of 36 years.
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PMID:Myocardial infarction under the age of 36: prevalence of thrombophilic disorders. 1573 21


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