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P01.152 Evaluation of Factor V Leiden variant as risk a factor for venous thromboembolism in glioblastoma patients

ABSTRACT: Abstract Introduction Venous thromboembolic events (VTE) are common complications in patients with glioblastoma (GBM). Factor V Leiden (FVL) polymorphism (rs6025, c.1601 G>A) is a known risk factor for VTE, evaluated in cancer associated thrombosis (CAT) in different tumor types. Little is known about the role of this variant in development of CAT in patients with GBM. Material and Methods A cohort of 116 GBM patients (73 males and 43 females) all treated with concomitant temozolomide and radiotherapy, were genotyped for FVL using PCR- pyrosequencing. Of the cohort, 40 patients were diagnosed with and 76 without VTE. Allele frequencies of respective variant were also compared with data from the SweGen Variant Frequency Browser (https://swegen-exac.nbis.se/). Statistical analyses in regard to VTE and its association with FVL and prognostic factors were performed. Results The variant A/G of FVL was carried by 17 (15%) of the patients and 99 (85%) were wild type, G/G. Chi2 test including the prognostic factors age, type of surgery, gender and blood group showed that these were evenly distributed between those with G/G and A/G, except for blood group in relation to FVL variant, which showed a borderline significance (p=0.07). Among the patients having blood group 0, 32% (n= 32) were G/G and 59% (n= 10) were A/G. Statistical tests did not reveal any correlation between blood group and FVL variant. In the logistic regression analysis apart from FVL, age, gender and blood group were included. This showed a significant difference for blood group 0 versus non-0 (A, B or AB) for decreased risk of VTE (P=0.014). There was no significant difference between heterozygous FVL (A/G) versus the G/G genotype in VTE risk (p=0.09). There were no differences in survival in relation to VTE or not or variant of FVL. The FVL AG variant is slightly overrepresented among GBM compared to the normal Swedish population, but does not reach statistical significance, OR 1.63 (0.93–2.84). Conclusions We examined the influence of FVL variants together with clinical factors in a homogenously treated cohort of GBM patients for the risk to develop a VTE. We confirmed blood group 0 versus non-0 as reducing the VTE risk. For FVL c.1601 G>A variant, the differences between AG vs GG did not reach statistical significance. In our cohort we found a trend towards increased risk of developing GBM for the A/G variant. We plan to further study other factors involved in coagulation for their potential role in GBM patients.

SUBMITTER: Heenkenda M

PROVIDER: S-EPMC6143968 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Project description:BackgroundABO blood type locus has been reported to be an important genetic determinant of venous and arterial thrombosis in genome-wide association studies. We tested the hypothesis that ABO blood type alone and in combination with mutations in factor V Leiden R506Q and prothrombin G20210A is associated with the risk of venous thromboembolism and myocardial infarction in the general population.MethodsWe used data from 2 Danish studies that followed members of the general public from 1977 through 2010. We obtained the genotype of 66 001 white participants for ABO blood type, factor V Leiden R506Q and prothrombin G20210A. We calculated hazard ratios (HRs) and population attributable risk. Our main outcome measures were venous thromboembolism and myocardial infarction.ResultsThe multivariable adjusted HR for venous thromboembolism was 1.4 (95% confidence interval [CI] 1.3-1.5) for non-O blood type (v. O blood type). For the factor V Leiden R506Q mutation, the adjusted HR was 2.2 (95% CI 2.0-2.5) for heterozygous participants and 7.0 (95%CI 4.8-10) for homozygous participants (v. participants without the mutation). For prothrombin G20210A, the adjusted HR was 1.5 (95%CI 1.2-1.9) for heterozygous participants and 11 (95% CI 2.8-44) for homozygous participants (v. participants without the mutation). When we combined ABO blood type and factor V Leiden R506Q or prothrombin G20210A genotype, there was a stepwise increase in the risk of venous thromboembolism (trend, p<0.001). The population attributable risk of venous thromboembolism was 20% for ABO blood type, 10% for factor V Leiden R506Q and 1% for prothrombin G20210A. Multivariable adjusted HRs for myocardial infarction by genotypes did not differ from 1.0.InterpretationABO blood type had an additive effect on the risk of venous thromboembolism when combined with factor V Leiden R506Q and prothrombin G20210A mutations; blood type was the most important risk factor for venous thromboembolism in the general population.

Project description:Importance:Although malignancy is an established risk factor for venous thromboembolism (VTE), the risk of VTE specifically in patients with keratinocyte carcinoma (KC) has not been previously studied. Objective:To determine the risk of VTE in patients with KC compared with patients not diagnosed with cancer and with patients diagnosed with common malignant neoplasms associated with VTE. Design, Setting, and Participants:Population-based retrospective analysis of patient insurance claims made between January 1, 2007, and December 31, 2014, from the Truven MarketScan Commercial and Medicare Supplemental Databases. Patients treated across the United States were divided into 3 cohorts: patients with KC, patients with pancreatic cancer or acute myelogenous leukemia who are thus at high risk for VTE, and patients without a history of common malignant neoplasms. Patients were excluded from the KC cohort if they had a history of another type of cancer. Data were analyzed between April 1, 2017, and January 15, 2018. Main Outcomes and Measures:Diagnosis of VTE within 1 year following the index date (for the KC and high-risk cohorts, the date of the initial diagnosis of cancer; for the control cohort, the date following 365 days of continuous insurance enrollment). Logistic regression was used to assess the risk of VTE in the KC cohort compared with the high-risk and control cohorts before and after matching across patient characteristics and known risk factors for VTE. Results:Of 5 753 613 potentially eligible patients, the final sample consisted of 740 246 patients (12.8%) across 3 cohorts. Of the 740 246 study participants, 417 839 were in the KC cohort (223 986 [53.6%] men, mean [SD] age, 64.2 [13.6] years); 314 736 were in the control cohort (135 203 [43.0%] men, 42.9 [15.2] years); and 7671 were in the high-risk cohort (3502 [45.7%] men, 59.4 [14.4] years) The risk of VTE in the KC cohort was lower compared with the high-risk cohort in univariable analysis (odds ratio [OR], 0.22; 95% CI, 0.20-0.23; P < .001), multivariable analysis (OR, 0.29; 95% CI, 0.26-0.32; P < .001), and after matching across patient characteristics and known risk factors (OR, 0.52; 95% CI, 0.35-0.78; P = .001). The risk of VTE in the KC cohort was higher in the univariable analysis (OR, 2.31; 95% CI, 2.23-2.41; P < .001), lower in the multivariable analysis (OR, 0.85; 95% CI, 0.80-0.90; P < .001), and not different after matching of patient characteristics and risk factors (OR, 0.95; 95% CI, 0.89-1.01; P = .08) than that of the control cohort. Conclusions and Relevance:The results of this study provided no evidence supporting the increased risk of VTE in the KC cohort compared with the control cohort. Given the inherent risks of chemoprophylaxis, the need for prophylactic anticoagulation in patients with KC who are scheduled for surgery should be carefully considered. Level of Evidence:NA.

Project description:ImportanceThe size of the risk of recurrent venous thromboembolism (VTE) after surgery in patients with a history of VTE is not well known.ObjectivesTo estimate the risk of and to identify the factors associated with recurrent VTE in patients undergoing surgery who have a history of VTE.Design, setting, and participantsThis population-based, follow-up cohort study includes patients with VTE who participated in the Multiple Environment and Genetic Assessment (MEGA) study. Original data were collected from March 1999 to April 2010. Data analysis began in June 1999 and ended in April 2010.ExposuresSurgery following a first VTE.Main outcomes and measurementsKaplan-Meier analyses were used to estimate cumulative incidences of recurrent VTE. Cox regression with a time-dependent covariate (surgery) was used to calculate the hazard ratio (HR) for developing recurrent VTE after surgery compared with no surgery.ResultsOverall, 3741 patients (mean [SD] age, 48.4 [12.8] years; 2020 [54.0%] women) with a history of VTE were included in the analysis, amounting to 18 899 person-years, with a median (interquartile range) follow-up of 5.7 (3.0-7.2) years. Of the 3741 patients, 580 (15.5%) underwent surgery and 601 (16.1%) developed a recurrent thrombotic event. The 1-month cumulative incidence of recurrent VTE for all surgery types was 2.1% (95% CI, 1.2%-3.6%), which increased to 3.3% (95% CI, 2.1%-5.1%) at 3 months and 4.6% (95% CI, 3.1%-6.6%) at 6 months. At 6 months, risk of recurrent VTE ranged from 2.3% to 9.3%, depending on surgery type. In addition to surgery type, factor V Leiden mutation (HR, 3.4; 95% CI, 1.6-7.4) and male sex (HR, 2.7; 95% CI, 1.3-5.8) were associated with increased risk of recurrent VTE.Conclusions and relevanceSurgery was associated with an increased risk of recurrent VTE in patients with a history of VTE; risk remained high for up to 6 months after the procedure. This study suggests that high-risk individuals may be identified based on surgery type, sex, and the presence of factor V Leiden mutation. These findings stress the need for revision of the current thromboprophylactic approach to prevent recurrence in these patients.

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P01.152 Evaluation of Factor V Leiden variant as risk a factor for venous thromboembolism in glioblastoma patients

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