Presence Of Factor V Leiden Mutation Research Articles

Determination of vWF, ADAMTS-13 and Thrombospondin-1 in Venous Thromboembolism and Relating Them to the Presence of Factor V Leiden Mutation.

Thrombophilia in venous thromboembolism (VTE) is multifactorial. Von Willebrand factor (vWF) plays a major role in primary hemostasis. While elevated vWF levels are well documented in VTE, findings related to its cleaving protease (ADAMTS-13) are contradicting. The aim of this study was to determine vWF, ADAMTS-13, and the multifactorial Thrombospondin-1 (TSP-1) protein levels in patients after 3-6 months following an unprovoked VTE episode. We also explored a possible association with factor V Leiden (FVL) mutation. vWF, ADAMTS-13 and TSP-1 were analyzed using ELISA kits in 60 VTE patients and 60 controls. Patients had higher levels of vWF antigen (P = .021), vWF collagen-binding activity (P = .008), and TSP-1 protein (P < .001) compared to controls. ADAMTS-13 antigen was lower in patients (P = .046) compared to controls but ADAMTS-13 activity was comparable between the two groups (P = .172). TSP-1 showed positive correlation with vWF antigen (rho = 0.303, P = .021) and negative correlation with ADAMTS-13 activity (rho = -0.244, P = .033) and ADAMTS-13 activity/vWF antigen ratio (rho = -0.348, P = .007). A significant association was found between the presence of FVL mutation and VTE (odds ratio (OR): 9.672 (95% confidence interval (CI) 2.074-45.091- P = .004), but no association was found between the mutation and the studied proteins (P > .05). There appears to be an imbalance between vWF and ADAMTS-13 in VTE patients even after 3-6 months following the onset of VTE. We report that the odds of developing VTE in carriers of FVL mutation are 9.672 times those without the mutation, but the presence of this mutation is not associated with the studied proteins.

Association of factor V Leiden mutation with retinal vein thrombosis in a set of Iraqi patients

Background: Retinal vein occlusion is the most common retinal vascular disorder after diabetic retinopathy with several ocular and systemic disorders associated with retinal veins thrombosis. Factor V Leiden (FVL) mutation as part of inherited thrombophilia may associated with retinal vein thrombosis. Objectives: Determine the presence of FVL mutation in a set of Iraqi patients with retinal vein thrombosis and evaluate its role in the etiology of thrombosis in those patients. Patients, Materials and Methods: A case-control study conducted for 6 months, a total number of 69 patients who were diagnosed with retinal vein thrombosis while attending ophthalmology outpatient clinic in Diwania city in Iraq. Only sixty patients were eligible for the study. From each patient, venous blood was withdrawn for complete blood count, blood film, erythrocyte sedimentation rate, kaolin clotting time, anticardiolipin antibodies, antinuclear antibody, thyroid-stimulating hormone, renal function test, random blood sugar, and serum cholesterol in addition to determine the presence of FVL mutation by polymerase chain reaction (PCR)-restriction fragment length polymorphism. For 84 individuals of control group, only the presence of FVL mutation by PCR was done. Results: Sixty out of 69 patients with retinal vein thrombosis were eligible for the study. There were a total of 34 males and 26 females with a mean age of 49.1 ± 2.03 years with no significant statistical differences in mean age and sex between the patients and the control groups. The proportion of patients with FVL mutation was higher than that of control subjects, 21.7% versus 8.3% (P = 0.023). FVL mutation in patients group showing a significant risk factor to develop retinal vein thrombosis than control group (odd ratio: 3.043). Conclusions: FVL plays a role in etiology of retinal vein thrombosis and measurement of this mutation with proper prophylaxis may be useful in prevention of venous thrombosis.

Factor V Leiden Mutation Is a Risk Factor for Hepatic Artery Thrombosis in Liver Transplantation

BackgroundHepatic artery thrombosis (HAT) after orthotopic liver transplantation (OLT) is associated with significant morbidity and mortality. Factor V Leiden (FVL) mutation is the most common genetic defect that predisposes to thrombosis. The reconstruction of hepatic artery with arterial graft is a documented risk factor for HAT. However, the relationship among FVL mutation, arterial graft, and HAT remains to be determined. MethodsWe randomly genotyped 485 patients who underwent OLT from April 2002 to January 2011 and studied the incidence of Hepatic artery thrombosis in the presence of FVL mutation. ResultsOf 485 patients, 21 patients (4.3%) developed HAT (13 male, 8 female); 10 patients (4 male, 6 female) were heterozygous for the FVL mutation. The incidences of HAT in patients without versus with the FVL mutation were 3.8% and 30% (P = .007). Of patients with HAT, 8 hepatic arteries were reconstructed with infrarenal aortic conduits. All 3 patients (100%) with vs 5 (28%) without FVL who received arterial grafts developed HAT (P = .042). ConclusionOur study suggested that the FVL mutation may be a risk factor for HAT in liver transplantation; the risk is augmented in the presence of an arterial graft.

Should factor V Leiden mutation and prothrombin gene polymorphism testing be done in women with recurrent miscarriage from North India?

Role of thrombophilic factor (FV) in the etiology of recurrent miscarriages is not confirmed till date. It has been hypothesized that thrombophilic G1691A factor V Leiden (FVL), if detected well ahead in time among recurrent miscarriages may be a treatable. The role of FVL mutation in the pathogenesis of sporadic and recurrent miscarriages among North Indian women was studied to construct the frequency data in this part of the country. Further, we have evaluated the cost-benefit factor. This is a case-control study, women with recurrent miscarriages (n = 1,000) as cases and healthy parous women (n = 500) as controls were enrolled in the study between January 2003 and January 2012. DNA was extracted from peripheral blood and analyzed for the presence of FVL mutation and prothrombin gene polymorphism (G20210A). We have carried out the meta-analysis taking into consideration 20 other world populations. In total, 50 (5.0 %) cases and 12 (2.4 %) controls were heterozygous for the FVL mutation. The incidence of FVL was higher in recurrent miscarriage cases as compared to the control group (OR 2.14; 95 % CI 1.12-4.05). Our results revealed the absence of FVL mutation in a homozygous state among patients and controls. Although the heterozygous mutation is almost double in cases as compared to controls, we still suggest that looking at the cost-benefit analysis this test may not be included in the battery of tests performed on recurrent miscarriages among North Indians from this part of the country.

High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis

Among candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control "EDITH" study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by the American College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2-18). Prophylaxis was judged as adequate in 116 cases (88.5%) and in 129 controls (87.2%) (p=0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p=0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomatic VTE occurring after surgery despite prophylaxis.

Racial differences in the prevalence of Factor V Leiden mutation among patients on chronic warfarin therapy

We report the prevalence of Factor V Leiden (FVL) in European American and African American patients on warfarin therapy residing in Alabama. Methods. Detailed history was obtained and FVL genotype was determined for 288 patients enrolled in a prospective cohort: Pharmacogenetic Optimization of Anticoagulation Therapy. Racial differences in genotype frequency were assessed by the Chi-square statistics and HWE assumptions by G-statistics. Race-specific analysis for the association between site of thromboembolism and the presence of FVL mutation was assessed using logistic regression. Results. The overall heterozygote (GA genotype) frequency was 4.9%. No patient was found to be homozygous (AA) for the variant allele. The prevalence of GA was higher in European American (8.6%) compared to African American (1.4%) patients ( p = 0.004). The FVL genotype frequency was significantly different across race for venous thromboembolic events ( p = 0.014) but not for arterial thromboembolic events ( p = 0.20). Multivariable race-specific analysis highlights the contribution of FVL mutation to the risk of venous thromboembolic events in European American ( p = 0.03) but not in African American patients ( p = 0.95). European American patients with the GA mutation were approximately 6.3 times more likely to have experienced a venous, rather than arterial thromboembolic event. Conclusion. In Alabama, among patients on warfarin, the GA genotype is more prevalent in European Americans compared to African Americans. In European Americans, but not in African Americans, the GA genotype was more prevalent in patients with venous compared to arterial thromboembolic events.

The Prevalence and Clinical Significance of Inherited Thrombophilic Risk Factors in Patients with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is defined as the occurrence of thrombosis and/or recurrent fetal losses in association with the presence of antiphospholipid antibodies (APLA). Although it has been suggested that APLA have a pathogenic role in the thrombotic complications of APS, pathogenicity of APLA has not been conclusively proven. It has been speculated that other inherited or acquired thrombogenic risk factors might influence the development of thrombosis in patients with APS. In the present study, we examined the effect of well known inherited thrombophilic risk factors (inherited protein C (PC), protein S (PS) and antithrombin (AT) deficiencies; factor V Leiden (FVL) G1691A mutation, and prothrombin G20210A mutation) in the development of thrombosis in APS patients. Seventy-three definite APS patients with arterial and venous thrombosis (group 1: APS patients with thrombosis), 29 antiphospholipid antibody-positive patients with first trimester abortus and/or thrombocytopenia and no history of thrombosis (group 2: APLA-positive patients without thrombosis), and 126 healthy controls (group 3) were included into the study. PC, PS, and AT deficiencies were screened with functional assays; the presence of FVL mutation and prothrombin mutation were detected by polymerase chain reaction. PS and AT activities were found to be normal in all groups. Only a single APS patient with thrombosis had been found to have PC deficiency, PC activities were normal in both APLA-positive patients without thrombosis and healthy controls. The frequencies of FVL A allele for APS patients with thrombosis, APLA-positive patients without thrombosis, and healthy controls were 10.4%, 6.8%, and 4.9%, respectively. The frequency of FVL A allele was significantly higher in APS patients with thrombosis compared with healthy controls (10.4% vs 4.9%, p= 0.02 with chi-square test). The frequencies of prothrombin A allele for APS patients with thrombosis, APLA-positive patients without thrombosis and healthy controls were 3.4%, 0%, and 1.3%, respectively. Although the frequency of A allele was higher in APS patients with thrombosis compared with both APLA-positive patients without thrombosis and healthy controls, it was not statistically significant. Our results showed that inherited PC, PS, AT deficiencies, and prothrombin G20210A mutation are not common in patients with APS. FVL G1691A mutation may contribute to the development of thrombosis in a small group of APS patients. This study suggests that the known inherited thrombophilic risk factors are not responsible for the development of thrombosis in the majority of APS patients. Further prospective studies in larger cohorts of patients are needed to delineate the exact role of thrombophilic mutations in the development of thrombosis in APS.

Prevalence of the factor VLeiden mutation among autopsy patients with pulmonary thromboembolic disease using an improved method for factor VLeiden detection.

Activated protein C resistance caused by factor VLeiden mutation is the most common inherited predisposing cause of venous thromboembolism, including pulmonary embolism (PE). We studied whether the incidence of factor VLeiden is higher among patients with PE evident at autopsy than in the general population. Paraffin-embedded fixed tissue blocks from all autopsy patients with diagnosed pulmonary thromboembolic disease during a 4-year period were collected for DNA extraction. Extraction and molecular analysis of the DNA was performed with an improved technique with an internal control to determine the presence of factor VLeiden mutation. Analysis of 82 autopsy cases with PE yielded 5 patients who were heterozygotes. Seventy-seven of the 82 patients analyzed were normal, and no homozygotes for factor VLeiden mutation were identified. This yielded a positive rate of 6% overall and 7% among white patients, which is similar to the incidence of heterozygotes in the white population. This study indicates that routine determination of factor VLeiden mutation is not warranted for patients with PE diagnosed at autopsy.