Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
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.
 ...
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.
 ...
PMID:Perinatal aspects of inherited thrombophilia. 1062 6

Recent studies of current oral contraceptives indicate that the risk of cardiovascular sequelae is low in young (age 20-24 years) reproductive-aged women. Venous thromboembolism remains the one event that occurs in users independent of the presence of risk factors. However, the attributable risk is small, in the range of 7 to 18 events per 100,000 women annually. This risk is proportional to estrogen dose until the level of 30-35 microg is reached; type of progestin may also influence risk, though recent studies are controversial. Modifiable risk factors for venous thromboembolism include the presence of hemostatic disorders, especially factor V Leiden, and perhaps obesity. Stroke is even more uncommon, with an attributable risk of about 1.5 events per 100,000 women annually. Cigarette smoking and hypertension are modifiable risk factors for both ischemic and hemorrhagic stroke; use of preparations with 50 microg of estrogen or higher and migraine headaches are risk factors for ischemic stroke. Eliminating risk factors among users substantially reduces the risk of ischemic stroke and virtually eliminates the risk of hemorrhagic stroke. Myocardial infarction is rare among young women, occurring at a rate of about 0.2 event per 100,000 women annually. Oral contraceptive users who are non-smoking and normotensive do not have an increased risk of myocardial infarction. However, the presence of these risk factors along with age acts synergistically to increase the risk among oral contraceptive users.
 ...
PMID:Cardiovascular issues with oral contraceptives: evidenced-based medicine. 1083 Nov 86

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.
 ...
PMID:Epidemiology of venous thromboembolic disease. 1176 74

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.
 ...
PMID:Tentative guidelines and practical suggestions to avoid venous thromboembolism during oral contraceptive therapy. 1212 Oct 63

"Traveller's thrombosis" is defined as a deep venous thrombosis of the leg that develops no later than two weeks following a journey lasting at least five hours. According to the WHO, traveller's thrombosis affects in particular persons with additional risk factors. These include obesity, age, such prior diseases as malignant tumours, previous surgery, use of oral contraceptives, and such inborn risk factors as antithrombin III deficiency and homozygous factor V Leiden mutation. In such patients, the (air) journey is merely the triggering event. Prophylactic measures should include counseling of high-risk patients. Depending on the risk profile, recommended general measures are compression and low-molecular-weight heparin. The much discussed use of acetylsalicylic acid, in contrast, is no certain prophylaxis.
 ...
PMID:[Traveler's thrombosis. Who is at risk--how to prevent it?]. 1239 1

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.
 ...
PMID:Genetic polymorphisms associated with acute pulmonary embolism and deep venous thrombosis. 1257 Jan 4

Inherited thrombophilias are associated with an increased risk of venous thromboembolism (VTE) and the risk is further increased during pregnancy. However, not all pregnancies or all thrombophilias carry the same risk. Deficiencies in coagulation inhibitors and especially in antithrombin are rare but are associated with a higher risk than the most frequent factor V Leiden or prothrombin (factor II) 20210A mutations. Differences may be observed depending on heterozygosity or homozygosity of the defects and on the presence of combined thrombophilias. Although we now have more information on the global risk of thrombosis in thrombophilia, the magnitude of the risk is unknown in women who do or do not have a history of VTE, and in those who are the propositus or family members. Additional risk factors may be taken into account such as age of the mother, cesarean section, obesity, and immobilization during pregnancy. Recommendations of the American College of Chest Physicians (ACCP) concerning prophylaxis during pregnancy published in 2001 are mostly 1C recommendations; they are based on observational studies and subject to changes when more information becomes available. There is now a consensus about prevention in the postpartum period in women with thrombophilia. In contrast, prophylaxis in the antepartum period is often determined on an individual basis. We give some indications of the appropriate prophylaxis on the basis of the ACCP recommendations and personal experience.
 ...
PMID:Inherited thrombophilia and gestational venous thromboembolism. 1270 16

Venous thromboembolism (VTE) is not a feature of thrombotic thrombocytopenic purpura (TTP), but there has been a recent report of VTE in association with plasma exchange (PEX) treatment for TTP using the solvent detergent (SD) plasma, PLAS+SD. We reviewed the occurrence of VTE in 68 consecutive patients with TTP (25 men, 43 women). Eight documented VTE events [six deep venous thromboses (DVTs), three pulmonary emboli] were identified in seven patients (all female) during PEX therapy. All six DVTs were associated with central lines at the site of thrombosis. Other known precipitating factors included pregnancy, immobility, obesity and factor V Leiden heterozygosity. VTE occurred at a mean of 53 d following the first PEX. The European SD plasma, Octaplas was the last plasma to be used in PEX prior to the VTE in 7/8 events. This is the first report of VTE following Octaplas infusion. VTE is a multifactorial disease and, although several known precipitating factors were present in all patients in this study, the use of large volumes of SD plasma in PEX may be an additional risk factor. We recommend prevention of VTE with graduated elastic compression stockings (class I) at diagnosis and prophylactic low-molecular-weight heparin once the platelet count rises above 50 x 10(9)/l.
 ...
PMID:Venous thromboembolism associated with the management of acute thrombotic thrombocytopenic purpura. 1278 Jul 94

The resistance to activated protein C (APC-resistance) based on the presence of factor V Leiden (F V Leiden) is the most frequent thrombophilic condition in the white race population. It contributes to the origin of thrombosis especially in the venous part of blood vessels. Significant geographic differences have been detected within Europe. The aim of this retrospective study was to determine the frequency in the occurrence of F V Leiden: 1. in healthy (asymptomatic) Slovak population, 2. in their consanguineously unrelated members with thrombosis and 3. in patients with myocardial infarction (IM) without or with other known risk factors of this disease (nicotinism, obesity, hypertension, dyslipoproteinemia, diabetes mellitus), respectively. The detection of FV Leiden was made by molecular biology methods. The occurrence in a group of 152 healthy individuals was four % (6 persons) and this frequency corresponds to the geographic localization of the Slovak Republic in Europe. In a group of 349 patients with thrombosis in anamnesis, FV Leiden was detected in 103 persons (29.5%). The occurrence was higher than the usually reported incidence in these patients (20%). Likewise, in a group of 35 patients with IM without risk factors in anamnesis, the occurrence of FV Leiden (8.6%) was significantly higher in comparison with healthy population and the incidence further increased significantly in a group of 41 patients with IM and the presence of at least one risk factor (14.6%). The authors therefore suppose an active role of the Leiden mutation of FV gene in the pathogenesis of this disease.
 ...
PMID:[Factor V Leiden and the Slovak population]. 1468 80


1 2 3 4 Next >>