Risk Of First Venous Thromboembolism Research Articles

Relationship between neighborhood socioeconomic status and venous thromboembolism: results from a population‐based study

Background The association between socioeconomic status and arterial cardiovascular disease is well established. However, despite its high burden of disability-adjusted life years, little research has been carried out to determine whether socioeconomic status is associated with venous thromboembolism. Objective To determine if neighborhood socioeconomic status is associated with venous thromboembolism in a population-based study from the Netherlands. Methods We identified all patients aged 15 years and older with a first event of venous thromboembolism from inhabitants who lived in the urban districts of The Hague, Leiden and Utrecht in the Netherlands in 2008-2012. Neighborhood socioeconomic status was based on the status score, which combines educational level, income and unemployment on a four-digit postal code level. Incidence rate ratios of venous thromboembolism were calculated for different levels of neighborhood socioeconomic status, with adjustments for age and sex. Results A total of 7373 patients with a first venous thromboembolism (median age 61 years; 50% deep vein thrombosis) were identified among more than 1.4 million inhabitants. Higher neighborhood SES was associated with lower incidence of VTE. In the two highest status score groups (i.e. the 95-99th and > 99th percentile), the adjusted incidence rate ratios were 0.91 (95% confidence interval [CI], 0.84-1.00) and 0.80 (95% CI, 0.69-0.93), respectively, compared with the reference status score group (i.e. 30-70th percentile). Conclusions High neighborhood socioeconomic status is associated with a lower risk of first venous thromboembolism.

Variation in the risk of venous thromboembolism following colectomy.

Guidelines recommend extended thromboprophylaxis following colectomy for malignant disease, but not for non-malignant disease. The aim of this study was to determine absolute and relative rates of venous thromboembolism (VTE) following colectomy by indication, admission type and time after surgery. A cohort study of patients undergoing colectomy in England was undertaken using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care data (2001-2011). Crude rates and adjusted hazard ratios (HRs) were calculated for the risk of first VTE following colectomy using Cox regression analysis. Some 12,388 patients were identified; 312 (2·5 per cent) developed VTE after surgery, giving a rate of 29·59 (95 per cent c.i. 26·48 to 33·06) per 1000 person-years in the first year after surgery. Overall rates were 2·2-fold higher (adjusted HR 2·23, 95 per cent c.i. 1·76 to 2·50) for emergency compared with elective admissions (39·44 versus 25·78 per 1000 person-years respectively). Rates of VTE were 2·8-fold higher in patients with malignant disease versus those with non-malignant disease (adjusted HR 2·84, 2·04 to 3·94). The rate of VTE was highest in the first month after emergency surgery, and declined from 121·68 per 1000 person-years in the first month to 25·65 per 1000 person-years during the rest of the follow-up interval. Crude rates of VTE were similar for malignant and non-malignant disease (114·76 versus 120·98 per 1000 person-years respectively) during the first month after emergency surgery. Patients undergoing emergency colectomy for non-malignant disease have a similar risk of VTE as patients with malignant disease in the first month after surgery.

Prospective study of plasma D-dimer and incident venous thromboembolism: The Atherosclerosis Risk in Communities (ARIC) Study

IntroductionPlasma D-dimer is a useful clinical test for acute venous thromboembolism (VTE), and concentrations remain higher in VTE patients after treatment than in controls. Yet, evidence is limited on whether higher basal D-dimer concentrations in the general population are associated with greater risk of first VTE. ObjectiveTo assess the prospective association between D-dimer and incident VTE over a long follow-up. MethodsWe measured plasma D-dimer in 12,097 participants, initially free of VTE, in the Atherosclerosis Risk in Communities Study. Over a median follow-up of 17years, we identified 521 VTEs. We calculated hazard ratios of VTE using proportional hazards regression. ResultsThe age, race, and sex adjusted hazard ratios of VTE across quintiles of D-dimer were 1, 1.5, 1.8, 2.1, and 3.2 (p for trend <0.0001). For the first 10years of follow-up, the hazard ratio for the highest versus lowest quintile was 3.5, and was 2.9 after 10years. In both whites and African Americans, VTE risk remained strongly associated with D-dimer after further adjustment for diabetes, body mass index, kidney function, and several thrombophilia genetic markers. D-dimer was associated with both unprovoked and provoked VTE, but more strongly with unprovoked. ConclusionsA higher basal level of plasma D-dimer in the general population, presumably reflecting a predisposition to thrombosis, is a strong, long-term risk factor for a first VTE.

Natural anticoagulants deficiency and the risk of venous thromboembolism: a meta-analysis of observational studies

IntroductionNatural anticoagulants deficiency (antithrombin [AT], protein C [PC], protein S [PS]) is a rare, but potent risk factor for venous thromboembolism (VTE). We performed a meta-analysis of observational studies evaluating the impact of inherited natural anticoagulants deficiency on VTE risk. Materials and MethodsCase–control and cohort studies evaluating the association of these abnormalities with VTE were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. ResultsTwenty-one studies were included in the analysis. Thirteen studies (3,452 cases and 11,562 controls) showed an increased risk of first VTE in AT deficient subjects compared to controls (OR: 16.26, 95%CI:9.90-26.70; P<0.00001). An increased risk of first VTE was also found in PC (11 studies, 2,554 cases and 9,355 controls; OR: 7.51, 95%CI:3.21-17.52; P<0.00001) and PS deficient patients (14 studies, 4,955 cases and 9,267 controls; OR: 5.37; 95%CI:2.70-10.67; P<0.00001) compared to controls. Evaluating the risk of VTE recurrence, we found a significant association with AT (4 studies, 142 cases and 1,927 controls; OR: 3.61; 95%CI:1.46-8.95; P=0.006) and with PC (2 studies, 80 cases and 546 controls; OR: 2.94; 95%CI:1.43-6.04; P=0.03), but not with PS deficiency (2 studies, 57 cases and 589 controls; OR: 2.52; 95%CI:0.89-7.16; P=0.08). Sensitivity and subgroup analyses confirmed these results. The association among natural anticoagulants deficiency and VTE was maximal for patients with unprovoked events. ConclusionThe VTE risk is increased in patients with natural anticoagulants deficiency, but additional studies are warranted to better assess the risk of VTE recurrence.

Risk of First Venous Thromboembolism in Pregnant Women in Hospital

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Journal Watch November 2013 – February 2014

Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England.

Risk of first venous thromboembolism in pregnant women in hospital: population based cohort study from England

Objective To examine the potential for preventing venous thromboembolism during and after antepartum hospital admissions in pregnant women.Design Cohort study using linked primary (Clinical Practice Research Datalink) and secondary (Hospital...

Risk of first venous thromboembolism in and around pregnancy: a population‐based cohort study

Knowledge of the absolute and relative risk of venous thromboembolism (VTE) in and around pregnancy would be crucial in identifying when to commence and cease thromboprophylaxis in women who would benefit from such intervention. We addressed this hypothesis using a large prospective primary care database from the United Kingdom, containing details on 972683 women aged 15-44years between 1987 and 2004. Risks of a first VTE during antepartum, postpartum and outside of pregnancy were compared using Poisson regression. The rate of VTE during the third trimester antepartum was six times higher than time outside pregnancy [Incidence Rate Ratio (IRR)=6·1; 95% confidence interval, 4·7-7·9]. In contrast, both the first (IRR=1·6) and second (IRR=2·1) trimesters conferred little increase in risk. The first 6weeks postpartum was associated with a 22-fold increase in risk, with the peak occurring in the first 3weeks. Increased age was found to be associated with VTE during postpartum and outside of pregnancy, but not during antepartum. Our findings of a notably raised risk of VTE persisting for 3 weeks postpartum and of a raised antepartum risk constrained to the third trimester have implications for modifying the current recommendations for VTE prophylaxis in pregnancy and the puerperium.

Thrombophilia and Cardiovascular Risk Factors On the Absolute Risk of First and Recurrent Venous Thrombosis. Results From a Retrospective Family Cohort Study Involving 2097 Relatives.

Abstract 2974Poster Board II-951 Introduction:Arterial and venous thromboembolism (VTE) share or seem to share cardiovascular risk factors such as older age, overweight and obesity, and possibly also hypertension, diabetes mellitus, dyslipidemia, and smoking. Little is known if subjects with common thrombophilia, (i.e. factor V Leiden, prothrombin G20210A or high factor VIII levels) are at higher risk of first or recurrent VTE due to cardiovascular risk factors. For subjects with rare thrombophilia (i.e. antithrombin, protein C or protein S deficiency), or non-carriers of thrombophilia no information is currently available whether contribution of cardiovascular risk factors increases the risk of first or recurrent VTE. Methods:In a multi-center retrospective cohort study of families with thrombophilia, we performed a post-hoc analysis to identify if relatives with rare thrombophilia, common thrombophilia, and relatives without one of these thrombophilic defects were at increased risk of first or recurrent VTE due to cardiovascular risk factors. Known cardiovascular risk factors were recorded: hypertension, hyperlipidemia, the presence of diabetes mellitus, smoking habits and overweight/obesity defined by body mass index (BMI) ≥25-30 kg/m2 or ≥30 kg/m2, respectively. Observation time for first VTE started at the age of 15, and for recurrent VTE on the date when initial anticoagulant treatment was withdrawn. Observation time ended on the date of first VTE or recurrence, respectively, or at date of enrollment. First, the absolute risk of first VTE for cardiovascular risk factors was calculated for the whole cohort. Sensitivity analyses were performed to assess the effect of idiopathic or provoked classification of initial thrombotic event and type of event (deep vein thrombosis or pulmonary embolism). When a positive association was found, a further stratification was subsequently made to analyze whether relatives with rare, common, or no thrombophilia influenced these risks. A Cox-proportional hazards model was used to evaluate risks between groups for adjustments of age and sex. Results:Of a total of 2097 relatives, 55% were female, 180 (12%) had first VTE at a median age of 35 years and 52 (2%) had a recurrence at a median age of 40 years. Of relatives, 20% had hypertension, 13% dyslipidemia, 5% diabetes mellitus, 22% were previous smokers, 35% were overweight and 15% were obese. Point estimates of adjusted hazard ratios in relatives with hypertension, hyperlipidemia, diabetes mellitus or previous smokers, compared to their reference groups ranged between 0.9 and 1.1 and were not statistically significant. Relatives with VTE were heavier than relatives without VTE (mean BMI 27.0 vs 25.5 kg/m2, P< 0.001); adjusted hazard ratio for each 1-point increase in BMI was 1.035 (95% CI, 1.010-1.066). Absolute risk of first VTE in normal weight, overweight or obese subjects was 0.16% (95% CI, 0.12-0.20), 0.20% (95% CI, 0.16-0.25), and 0.26% (95% CI, 0.19-0.36), respectively. Sensitivity analyses did not change these outcomes. Annual incidences of first VTE in non-carriers of thrombophilia, common thrombophilia carriers and rare thrombophilia carriers were 0.04%, 0.20% and 0.97%. In the non-carrier group, adjusted hazard ratios for first VTE in overweight or obese relatives were 6.1 (95% CI, 1.3-28.1) and 6.7 (95% CI, 1.2-37.6), compared to non-carriers of normal weight. In common thrombophilia carriers these risks were 1.7 (95% CI, 1.0-2.9) and 2.1 (95% CI, 1.2-3.8) fold increased. In rare thrombophilia carriers, overweight or obesity was not associated with an increased risk of first VTE (adjusted hazard ratios 0.8; 95% CI, 0.5-1.4 and 0.8; 95% CI, 0.4-1.7, respectively). For recurrence, overweight and obese relatives with common or rare thrombophilia seemed to have a slightly higher risk of recurrence than normal weight relatives, but the overall 10 year recurrence rate in both groups was similar. Conclusion:Venous thrombotic risk increases with increasing BMI in non-carriers and common thrombophilia carriers. This effect is overruled in carriers of rare thrombophilia, where a deficiency itself irrespective of BMI apparently is sufficient to generate very high risk of thrombosis. Overweight and obesity seemed to increase the risk of recurrence in carriers of both common and rare thrombophilia. Other cardiovascular risk factors did not increase the risk of VTE in this thrombophilic family cohort. Disclosures:No relevant conflicts of interest to declare.

Age at First Venous Thromboembolism and Risk of Recurrence

Risk of first venous thromboembolism (VTE) increases with age. We investigated whether age is related to the risk of recurrent VTE. We followed 694 patients for a mean of 40 months after first unprovoked proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE) and withdrawal of anticoagulants. We excluded patients with natural inhibitor deficiency, lupus anticoagulant, or cancer; patients who required indefinite anticoagulation; pregnant women; and women who had VTE related to female hormone use. The endpoint was symptomatic recurrent VTE.VTE recurred in 152 patients (22%). The adjusted hazard ratio (HR) of recurrence for a 10-year increase in age was 0.94 (95% confidence interval [CI], 0.82-1.08; p = 0.4). Compared with patients aged younger than 47 years (1st tercile of patient population) no significant increase in the risk of recurrent VTE was found among patients 47-61 years old (2nd tercile) or patients older than 61 years (3rd tercile) ([HR, 1.25; 95% CI, 0.78-2.01] and [HR, 0.93l; 95% CI, 0.56-1.53], respectively). Compared to patients older than 80 years, the HR of recurrence among patients younger than 50 years was 1.11 (95% CI, 0.11-10.3; p = 0.9). After 5 years, probability of recurrence was 32% (95% CI, 24%-40%) among patients aged less than 47 years; 21% (95% CI, 15%-28%) among patients 47-61 years old; and 33% (95% CI, 24%-42%) among patients older than 61 years (p = 0.5).Our results show that in patients with first unprovoked proximal DVT and/or PE, risk of recurrence is not related to age at first VTE. Regardless of age, these patients have a high risk of recurrence.

The risk of first venous thromboembolism during pregnancy and puerperium in double heterozygotes for factor V Leiden and prothrombin G20210A.

The risk of venous thromboembolism (VTE) during pregnancy in double heterozygous carriers of factor (F) V Leiden and prothrombin G20210A is not established. Hence, whether or not these women deserve antithrombotic prophylaxis when pregnant is unknown. In the frame of a multicenter family study, 52 double heterozygous carriers of FV Leiden and prothrombin G20210A who had remained pregnant at least once before knowledge of thrombophilia, were retrospectively investigated with respect to the occurrence of first VTE during pregnancy and puerperium. They were compared with 104 heterozygous carriers of FV Leiden, 104 of prothrombin G20210A and 104 women without thrombophilia. Double heterozygotes were similar to single heterozygous carriers and non-carriers for the age at first pregnancy, age at testing and rate of full-term pregnancies. No VTE during pregnancy was observed in the four groups of women, whereas in the puerperium it occurred in two double carriers (1.8% of pregnancies, 95% CI: 0.5-6.3), three single FV Leiden carriers (1.5%, 0.5-4.3), two single prothrombin G20210A carriers (1%, 0.2-3.6) and one non-carrier (0.4%, 0-2.5). The risk of first VTE during pregnancy and puerperium in double heterozygous carriers of FV Leiden and prothrombin G20210A is low and similar to that of single carriers. As for single heterozygotes, antithrombotic prophylaxis in asymptomatic double heterozygous carriers appears to be justified only in puerperium.

Low vitamin B6 levels and the risk of recurrent venous thromboembolism

Low plasma vitamin B6, measured as pyridoxal-5'-phosphate (PLP), is associated with an increased risk of first venous thromboembolism (VTE). In a prospective cohort of 757 patients with first VTE we investigated the association of PLP levels with risk of recurrent VTE. After 4 years, the likelihood of VTE recurrence among patients with PLP < or =23.3 nmol/L and 14.4% (11.5%-17.4%) among those with PLP >23.3 nmol/L was 22.5% (95% CI 13.6%-31.5%) (p=0.01). Patients with PLP ''23.3 nmol/L had 1.8-fold higher recurrence risk (1.01-3.14) than patients with PLP >23.3 nmol/L (adjusted for confounders including homocysteine). Therefore, low vitamin B6 is a risk factor of recurrent VTE.

G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism

OBJECTIVESThe study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden.BACKGROUNDSeveral inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial.METHODSA total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years.RESULTSA total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9–12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0–14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up.CONCLUSIONSIn a prospective evaluation of 218 men, the presence of prothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.