Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034065 (pulmonary embolism)
 14,979 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deficiency of the naturally occurring anticoagulant proteins, such as antithrombin, protein C and protein S, and activated protein C resistance due to the factor V Leiden gene mutation is associated with inherited thrombophilia. So far, no direct comparison of the thrombotic risk associated with these genetic defects is available. In this study, we wish to compare the lifetime probability of developing thrombosis, the type of thrombotic symptoms, and the role of circumstantial triggering factors in 723 first- and second-degree relatives of 150 index patients with different thrombophilic defects. We found higher risks for thrombosis for subjects with antithrombin (risk ratio 8.1, 95% confidence interval [CI], 3.4 to 19.6), protein C (7.3, 95% CI, 2.9 to 18.4) or protein S deficiency (8.5, 95% CI, 3. 5 to 20.8), and factor V Leiden (2.2, 95% CI, 1.1 to 4.7) than for individuals with normal coagulation. The risk of thrombosis for subjects with factor V Leiden was lower than that for those with all three other coagulation defects (0.3, 95% CI, 0.1 to 1.6), even when arterial and superficial vein thromboses were excluded and the analysis was restricted to deep vein thrombosis (0.3, 95% CI, 0.2 to 0.5). No association between coagulation defects and arterial thrombosis was found. The most frequent venous thrombotic manifestation was deep vein thrombosis with or without pulmonary embolism (90% in antithrombin, 88% in protein C, 100% in protein S deficiency, and 57% in factor V Leiden), but a relatively mild manifestation such as superficial vein thrombosis was common in factor V Leiden (43%). There was a predisposing factor at the time of venous thromboembolism in approximately 50% of cases for each of the four defects. In conclusion, factor V Leiden is associated with a relatively small risk of thrombosis, lower than that for antithrombin, protein C, or protein S deficiency. In addition, individuals with factor V Leiden develop less severe thrombotic manifestations, such as superficial vein thrombosis.
 ...
PMID:Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. 974 74

Thromboembolic episodes are common events and affect approximately one in 1,000 persons annually. Pulmonary embolism alone accounts for 50,000 to 100,000 deaths per year in the United States with > 50% of those being elderly persons. Resistance to activated protein C is the most common inherited disorder associated with hereditary thrombophilia. A missense mutation has been identified in the gene coding for coagulation factor V (codon 506) which renders this procoagulant factor resistant to inactivation by activated protein C resulting in an increased risk for venous thrombosis. Recently, a second polymorphism was identified in the prothrombin gene (factor II) which is also associated with increased risk for venous thrombosis. Because of the high prevalence of these two mutations in the general population as well as in specific patient populations, the ability readily to detect these two mutations must be feasible. In this study, we evaluated 303 patients for the prothrombin mutatin (G20210A) which were previously tested for the factor V mutation using established polymerase chain reaction-mediated restriction fragment length polymorphism assays. In these patients, 30 (9.9%) were found to be heterozygous for the factor V Leiden mutation with no homozygous mutants identified. Twenty individuals (6.6%) were heterozygous for the prothrombin G20210A mutation, and we identified two individuals (0.66%) who were homozygous for the 20210A allele. Of the total 303 individuals screened, two were double heterozygotes for both the factor V Leiden and the prothrombin gene mutations. We also describe a multiplex polymerase chain reaction-mediated restriction fragment length polymorphism assay for detecting both mutations in a single-tube double-enzyme digestion reaction making identification of these two mutations easily achievable.
 ...
PMID:Rapid multiplex analysis for the factor V Leiden and prothrombin G20210A mutations associated with hereditary thrombophilia. 978 36

It has been evident for over 30 years that combined oral contraceptive pills (OCP) increase the risk of venous thromboembolism. Recently, it has been suggested that there is an interaction between combined OCPs and the factor V Leiden mutation with the result that the relative risk of venous thromboembolism (VTE) is higher than expected in women who have this heritable thrombophilic defect using combined oral contraceptive pills. In Caucasian populations, factor V Leiden is very prevalent, being present in between 3 and 7% of Europeans and white North Americans. The high prevalence of the defect and its apparent interaction with combined oral contraceptive pills has led to the suggestion that all women should be screened for factor V Leiden prior to commencing contraceptive pills. Although the relative risk of VTE is very significantly increased in factor V Leiden positive women using contraceptive pills, the absolute incidence of venous thrombotic events is low and fatal pulmonary embolism is rare. It would be extremely costly to screen all women for the factor V Leiden mutation and unlikely to be deemed cost-effective. Widespread screening would result in 3-7% of women being denied the most effective and acceptable form of contraception and may influence negotiations with life insurers. It is suggested that only selected women, i.e. those with a personal history of previous venous thromboembolism and those with a clear family history of VTE are offered screening for thrombophilic defects.
 ...
PMID:Factor V Leiden: should all women be screened prior to commencing the contraceptive pill? 1022 5

We investigated the influence of the ABO blood group in the observed prevalences of the recently described factor V R506Q and factor II G20210A mutations in a thrombotic population. We determined the ABO blood group in a sample of 178 unselected patients (aged 17-83 years), diagnosed at our center with deep vein thrombosis or pulmonary embolism. The results of this study show a high prevalence of thrombosis in the non-O blood group. In the general population, the prevalence as a fraction of the O blood group was 2.69 (confidence interval 1.90-3.82). Of the factor V R506Q carriers (n = 28), only one had O group blood and 27 of 28 were non-O (24 A, one B and two AB). However, within the group of factor II G20210A carriers (n = 17), seven had O, nine A and one B type blood. The prevalence of the factor V R506Q mutation within the O blood group was 2.4% (one of 42), significantly lower than in the A group (23.3%, 24 of 103; P = 0.002), or in the overall non-O group (19.9%, 27 of 136; P = 0.006). This prevalence was similar to that observed previously in the non-thrombotic population in our area (3.5%; P = 0.9). We analyzed the clotting activity of factor VIII and we found higher levels in the non-O group (1.78+/-0.61 U/ml) than in the O blood group (1.30+/-0.51 U/ ml; P < 0.0001). We speculate that factor Va in individuals with the factor V Leiden mutation could interact with the high levels of factor VIII clotting activity as a necessary cofactor.
 ...
PMID:The O blood group protects against venous thromboembolism in individuals with the factor V Leiden but not the prothrombin (factor II G20210A) mutation. 1045 23

Appropriate thromboprophylaxis in hospital patients is effective in preventing clinically important venous thromboembolic events, including deep vein thrombosis (DVT) and fatal pulmonary embolism. Due to the risk of bleeding associated with pharmacological prophylaxis and the cost of administering prophylactic drugs, the clinical benefit and cost-effectiveness of thromboprophylaxis may be optimized by providing prophylaxis only to patients at risk of thrombosis, and tailoring the intensity of prophylaxis to the level of risk. Accurate assessment of patients' thromboembolic risk is therefore highly necessary. Thromboembolic risk is influenced by numerous factors. Several risk factor indices based on clinical risk factors and laboratory variables have been proposed since the 1970s, but these have not been widely adopted due to their complexity and lack of prospective validation. The method of deriving risk data on which these indices are based is questioned, and older prognostic indices excluded recently identified risk factors, particularly molecular factors such as the clotting factor V Leiden mutation, further undermining their clinical value. A number of much simpler risk assessment models (RAMs) have now been developed which stratify patients into low-, moderate- and high-risk categories. However, no RAM currently available provides comprehensive guidance for all patient groups. Use of poorly designed RAMs may fail to identify some patients at risk, leading to omission of prophylaxis and preventable thrombotic events. Certain patient groups develop DVT despite prophylaxis. Current RAMs are not validated to identify these patients. Well-designed and well-validated RAMs, incorporated into standard practice guidelines in hospitals, should contribute to improved clinical outcomes and economic benefits of prophylaxis.
 ...
PMID:Clinical limitations of risk assessment models. 1049 30

A retrospective investigation on the frequency of thrombotic events in 227 heterozygous and 16 homozygous carriers for the factor V R506Q mutation (factor V Leiden) from 102 unrelated families in the East Bohemian region is reported. A majority of 130 of the 227 (57%) heterozygous and a minority of 5 of 16 (31%) homozygous carriers for the factor V R506Q mutation remained asymptomatic. Deep venous thrombosis without pulmonary embolism in a minority was the main and the most frequent clinical manifestation in 97 of 243 carriers for the factor V R506Q mutation. Deep venous thrombosis occurred in 92 of 227 (41%) heterozygous and in 11 of 16 (69%) homozygous carriers of the factor V R506Q. Spontaneous thrombosis prevailed in symptomatic men. Thrombosis in women usually occurs during risk situations well known to elicit venous thrombosis. Oral contraceptives and pregnancy were significantly the most frequent risk factors in female carriers of the factor V R506Q mutation, which in fact can readily explain the lower average age for the first thrombotic event of 30.6 years in women compared to 37.1 years in men.
 ...
PMID:Risk of thrombosis in patients homozygous and heterozygous for factor V Leiden in the East Bohemian region. 1077 28

Identification of combined genetic factors in factor V Leiden carriers is important for a more accurate risk assessment for venous thrombosis (VT). Among these individuals, we evaluated the role of polymorphisms of the plasminogen activator inhibitor-1 (PAI-1) gene in the thrombophilic phenotype. A total of 382 factor V Leiden carriers were included in the study. This population was divided into 3 groups. Group 1 (n=168) included individuals with a personal history of VT; group 2 (n=140) included individuals without personal VT but with a familial history of VT; and group 3 (n=74) included individuals without VT and with a fortuitous discovery of the factor V Leiden mutation. We compared the genotype distribution of 2 polymorphisms, A -844G and -675 4G/5G, located in the promoter region of the PAI-1 gene among these 3 groups of individuals. The A -844G allele frequency differed significantly among the 3 groups (P=0.048), the A allele being more frequent in patients who suffered from VT (61%) than in subjects without VT (52%, P=0.015), whereas no difference was observed between the 2 groups of asymptomatic individuals. The prevalence of genotype AA carriers was higher in patients with VT (38%) than in asymptomatic individuals (21%, P=0. 015), leading to an odds ratio of 1.74 (95% confidence interval, 1.3 to 3.8). Carrying the AA genotype conferred a risk of deep VT of 2. 08 (95% confidence interval, 1.28 to 3.40), whereas it did not seem to significantly influence the risk of pulmonary embolism. Concerning the -675 4G/5G polymorphism, no significant difference was observed among the 3 groups, the 4G allele frequency being 0.54 (in group 1), 0.49 (in group 2), and 0.45 (in group 3). These data suggest a role for the -A844G PAI-1 gene polymorphism in the thrombophilic phenotype of factor V Leiden carriers.
 ...
PMID:The A -844G polymorphism in the PAI-1 gene is associated with a higher risk of venous thrombosis in factor V Leiden carriers. 1080 58

We report a case of a 35-year-old male with a history of recurrent thromboembolic events, who presented to the emergency room with right sided weakness and difficulty with speech. The patient's past medical history included two myocardial infarctions, two deep vein thromboses, and a pulmonary embolism. Subsequent laboratory evaluation indicated that the patient was heterozygous for both the factor V Leiden and prothrombin G20210A mutations. This case report emphasizes the importance of evaluating patients with suspected hereditary thrombophilia for both of these mutations.
 ...
PMID:Concurrent factor V Leiden and prothrombin G20210A gene mutations in a patient with a history of recurrent thrombosis. 1086 Feb 31

A diagnosis of recurrent venous thromboembolism is commonly suspected by physicians in the clinical setting. Many do not realize that recurrent venous thromboembolism may mimic the first venous thromboembolic event (VTE) and that only 20 to 30% of patients who have had a first VTE actually have objective recurrent thrombotic disease. Objective testing is necessary to prevent the misdiagnosis of thrombophilia in patients and the associated exposure to prolonged anticoagulant treatment that accompanies that diagnosis. In patients with clinically suspected recurrent venous thrombosis, compression ultrasonography in a new venous segment is the preferred diagnostic approach and contrast venography is an alternative test. There is insufficient evidence to know whether D-dimer testing is an effective approach to the diagnosis of thrombophilia. In patients with suspected recurrent pulmonary embolism, the diagnostic method should begin with ventilation/perfusion lung-imaging and a complementary pulmonary angiography when the results of initial tests are equivocal. Patients with recurrent venous thromboembolism should be treated with anticoagulants for longer than 6 months but the precise period depends on the patient's risk of bleeding as a result of the treatment. Finally, there is currently a lack of evidence that risk for recurrent VTE is increased in patients with a first episode of venous thromboembolism and heterozygous factor V Leiden mutation or the G2021OA prothrombin mutation.
 ...
PMID:Recurrent venous thromboembolism: diagnosis and management. 1091 42

We determined the prevalence of factor V Leiden and of prothrombin G20210A mutations in a cohort of unselected outpatients (n = 748) referred for suspected deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and a pooled analysis of similar studies was also performed. Based on the clinical presentation, the prevalence of factor V Leiden was 15.7% in the 83 patients with DVT and 14.1% in the 99 patients with PE compared with 5.3% in patients without DVT and/or PE (control group). The prevalence of the prothrombin G20210A mutation did not differ among the three groups (3.9% for controls, 4. 8% for DVT and 3.9% for PE patients). We then divided the 99 patients with PE by separately analysing those with PE but without DVT (n = 57) and those with PE and DVT (n = 42). Compared with the control group, the prevalence of factor V Leiden was 10.5%, odds ratio (OR) 2.10 [95% confidence interval (95% CI) 0.68-5.45] in patients with primary PE and 19.1%, OR 4.20 (95% CI 1.54-10.30) in patients with DVT and PE. For the prothrombin G20210A mutation, no statistically significant differences were found between the control group and the three other groups. In conclusion, our data and the pooled analysis indicate that patients with primary PE are less often affected by the factor V Leiden mutation. No statistically significant differences were observed between patients and controls for the prothrombin G20210A mutation.
 ...
PMID:Prevalence of factor V Leiden and prothrombin G20210A mutations in unselected patients with venous thromboembolism. 1093 Sep 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>