Lower Risk Of Venous Thrombosis Research Articles

Hormonal Contraceptives and the Risk of Venous Thrombosis.

The risk of venous thrombosis (VT) varies according to the type of progestogen that is found in combined oral contraceptives (COCs). When combined with the estrogen component ethinylestradiol (EE), the androgenic progestogens are better able to counteract the EE-induced stimulation of liver proteins and hence are associated with a twofold decreased risk of VT compared with non- or antiandrogenic progestogens, which exert limited counteraction of EE. Because EE is responsible for the increased risk, novel estrogens such as estradiol were developed and seem to have a lower risk of VT than EE. Besides COCs, there are other methods of hormonal contraceptives, such as progestogen-only contraceptives, which do not increase VT risk, except for injectables. Other nonoral contraceptives are combined vaginal rings and patches. There is insufficient evidence regarding the risk of VT associated with these two methods compared with COCs. The increased risk associated with COCs is more pronounced in women with inherited thrombophilia. In these women, the progestogen levonorgestrel seems to be associated with the lowest risk of VT. Currently, there are no studies that have investigated the risk of VT in women who switch COCs. We hypothesize that switching COCs, even when switching from a high- to a low-risk COC, increases the risk of VT. Finally, risk prediction models in women who use COCs are lacking. Since there is a large number of VT cases associated with COC use, it is important to identify women at risk of VT and advise them on alternative contraception methods.

Thrombin generation in newly diagnosed multiple myeloma during the first three cycles of treatment: An observational cohort study

BackgroundMultiple myeloma (MM) is associated with a high risk of thrombosis, particularly during the first months of treatment including immunomodulatory drugs (IMiDs). There is no consensus on prevention of thromboembolic risk in patients with de novo MM, and identification of patients requiring anticoagulant thromboprophylaxis remains challenging. Evaluating coagulability by an in vitro thrombin generation (TG) test might be a way of identifying such patients. ObjectiveTo determine whether TG assessment could reveal an increase in coagulability during the first three chemotherapy cycles. MethodsThis prospective and longitudinal observational study included patients newly diagnosed with MM. TG was determined in platelet‐rich and platelet‐poor plasma using calibrated automated thrombography with a low tissue factor (TF) concentration. ResultsSeventy‐one patients were enrolled, allowing TG analysis during 213 chemotherapy cycles. TG remained unchanged throughout follow‐up irrespective of treatment regimen, but values determined before cycles 2 and 3 were significantly higher in patients receiving iMiDs‐containing regimens. No association was found between TG and its changes and thrombosis occurrence during follow‐up: venous thrombosis in eight patients; no cardiovascular event. A significantly (87%) lower risk of venous thrombosis was observed in patients receiving prophylaxis with a low‐molecular‐weight heparin (LMWH; OR: 0.13 (95% CI: 0.02‐0.76). Neither bortezomib‐ nor dexamethasone‐containing regimens were associated with thrombotic risk. Changes in TG, as studied, were not associated with thrombotic events. ConclusionsThe only factor associated with a reduction in early thrombotic risk was prophylaxis with LMWH. The issue of how to identify patients requiring prophylactic anticoagulation remains unresolved.

Risk Factors for Arterial Versus Venous Thrombosis in Polycythemia Vera: Single Center Experience in 587 Patients

▪BackgroundA recent study from the International Working Group on Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) identified prior arterial events and hypertension as risk factors for subsequent arterial thrombosis and prior venous events and age 65 years or older as risk factors for venous thrombosis in polycythemia vera (PV) (Blood 2014;124:3021). In the current single center study, we sought to validate the aforementioned findings from the IWG-MRT and look into further details regarding arterial versus venous thrombosis in PV.MethodsStudy patients were selected from our institutional database of myeloproliferative neoplasms (MPN) and fulfilled the 2008 World Health Organization (WHO) criteria for the diagnosis of PV (Blood. 2009;114:937). Screening for the two most frequent mutations other than JAK2 (TET2 and ASXL1) were performed according to conventional methods (Leukemia. 2014;28:2206). Statistical analyses considered clinical and laboratory parameters obtained at time of diagnosis.ResultsPatient characteristics:Analysis was conducted on 587 patients (median age 60 years; 48% males). ASXL1 and TET2 mutational status was available in 133 patients. Among informative cases, 31% had palpable splenomegaly, 34% microcirculatory symptoms, 30% pruritus, 8% erythromelalgia, 42% hypertension, 9% diabetes and 11% were active tobacco users. TET2 and ASXL1 mutations were documented in 18% and 11%, respectively. During follow-up, 224 (38%) patients died and median follow-up for living patients was 109 months. Median survival was 16 years and leukemic or fibrotic transformations were documented in 4% and 14%, respectively.Thrombotic events:A total of 235 (40%) patients experienced at least one thrombotic event before or after diagnosis and included 153 (26%) arterial and 104 (18%) venous events. Thrombotic events were recorded before or at time of diagnosis in 146 (25%) patients and included 97 (17%) arterial and 55 (9%) venous events. Thrombotic events after diagnosis were recorded in 128 (22%) patients and included 82 (14%) arterial and 57 (10%) venous events.Associations for arterial, venous or all thrombotic events occurring at any time before or after time of diagnosis:The occurrence of any thrombotic event before or after diagnosis correlated with active tobacco use (p=0.04), diabetes history (p=0.03), hyperlipidemia (p=0.04) and major hemorrhage (p=0.03). The occurrence of any arterial event before or after diagnosis correlated with advanced age (p=0.006), diabetes history (p=0.005), hypertension history (p=0.004) and hyperlipidemia (p<0.0001). The occurrence of any venous event before or after diagnosis correlated with female sex (p=0.008), younger age (p<0.0001), lower platelet count (p=0.0014) and palpable splenomegaly (p=0.006). TET2 or ASXL1 mutations did not correlate with overall, arterial or venous thrombosis.Risk factors for arterial versus venous events after time of diagnosis:In univariate/multivariable analysis, thrombosis-free survival (TFS) was adversely affected by prior vascular events (p=0.002/0.03 multivariable) and increased leukocyte count (p=0.03/0.03); arterial thrombosis-free survival was adversely affected by prior arterial events (p<0.0001/P<0.0001), hyperlipidemia (p=0.001/0.03), hypertension (p=0.02/NS) and advanced age (p=0.02/NS); venous thrombosis-free survival was adversely affected by prior venous events (p=0.04/0.05), increased leukocyte count (p=0.0009/0.002), and younger age (p=0.02/NS). In addition, major hemorrhage at diagnosis was associated subsequent venous thrombosis in both univariate and multivariable analysis. TET2 or ASXL1 mutations did not affect the risk of overall, arterial or venous thrombosis.ConclusionsIn contemporarily managed patients with PV, prior vascular events predict future events for both arterial and venous thrombosis; additional risk factors included hyperlipidemia for arterial and increased leukocyte count for venous thrombosis. The current study also identifies association of arterial thrombosis in general with older age and history of hypertension, diabetes or hyperlipidemia whereas venous thrombosis was associated with younger age, female sex and palpable splenomegaly. Additional findings included association of major hemorrhage with thrombosis and higher platelet count with lower risk of venous thrombosis. DisclosuresNo relevant conflicts of interest to declare.

Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study

Whether vitamin supplements decrease venous thrombosis risk is controversial. Previous reports did not all take confounding fully into account, either by randomization or by extensive adjustment. The aim of our study was to determine whether vitamin supplementation decreases the risk of venous thrombosis. A large case-control study included 2506 patients with venous thrombosis, 2506 partner controls, and 2684 random-digit dialing (RDD) controls. When patients were compared with RDD controls, unconditional logistic regression was used to calculate ORs with 95% CIs. When patients were compared with partner controls, conditional logistic regression was used, providing further adjustment for unmeasured confounding. Vitamin use yielded a 37% lower risk of venous thrombosis than no vitamin use (OR: 0.63; 95% CI: 0.57, 0.70) when comparing patients with RDD controls. Adjustment for several putative confounders did not change the estimate (OR: 0.68; 95% CI: 0.61, 0.77). The fully adjusted ORs for vitamin A, vitamin B-6, vitamin B-12, folic acid, vitamin C, vitamin D, vitamin E, and multivitamin use were in the same range. However, when patients were compared with partner controls, ORs attenuated to unity. Results were similar for provoked and unprovoked events, as well as for deep vein thrombosis and pulmonary embolism. After extensive adjustments, vitamin supplementation was no longer associated with a decreased risk of venous thrombosis in this study. Previous positive results may have been spurious as a result of uncontrolled confounding.

Gamma Prime Fibrinogen and Childhood Obesity: Ready for Prime Time?

Gamma Prime Fibrinogen and Childhood Obesity: Ready for Prime Time?

Coffee consumption is associated with a reduced risk of venous thrombosis that is mediated through hemostatic factor levels

Coffee consumption is associated with a lower risk of venous thrombosis, but the role of confounding and the pathophysiology behind these findings are unclear. To assess the role of hemostatic factors in the relationship between coffee consumption and venous thrombosis. From a large case-control study, 1803 patients with a first venous thrombosis and 1803 partner controls were included. With conditional logistic regression, odds ratios (ORs) and 95% confidence intervals (CIs) for venous thrombosis were calculated for coffee consumption vs. no coffee consumption. In addition, mean differences in hemostatic factor levels between these groups were calculated in the controls. Coffee consumption yielded a 30% lower risk of venous thrombosis than no coffee consumption (OR 0.7, 95% CI 0.5-0.9). Adjustment for several putative confounders (age, sex, body mass index, smoking, hormonal factors, statin, aspirin, alcohol, malignancy, and chronic disease) yielded an OR of 0.8 (95% CI 0.6-1.1). Results were similar for provoked and unprovoked events, and for deep vein thrombosis and pulmonary embolism. In controls, von Willebrand factor levels were 11 (3-19) IU dL(-1) lower and factor (F) VIII levels were 11 (1-21) IU dL(-1) lower in coffee consumers than in non-consumers. After adjustment of the risk estimates for these hemostatic factors, the inverse association between coffee consumption and venous thrombosis diminished (OR 1.0, 95% CI 0.7-1.4). There was no association between coffee consumption and anticoagulant proteins, fibrinogen levels, or fibrinolytic markers. Coffee consumption is associated with a lower risk of venous thrombosis, which seems to be mediated through von Willebrand factor and FVIII.

Risk of venous thromboembolism in first- and second-generation immigrants in Sweden

Background There are ethnic differences in the incidence of venous thromboembolism. This is the first nationwide study to examine whether there is an association between country of birth in first-generation immigrants and first hospitalisation for venous thrombosis (VT) and pulmonary embolism (PE), and to study whether a similar association exists in second-generation immigrants. Methods The study is a nationwide follow-up study. The study subjects were first- and second-generation immigrants residing in Sweden between January 1, 1964 and December 31, 2007. The reference population comprised first- and second-generation Swedish-born individuals. Standardised incidence ratios (SIRs) for VT and PE, standardised with regard to age, geographic region of residence, time period, and socioeconomic status, were estimated by sex in first- and second-generation immigrants. Results First-generation male and/or female immigrants from Greece, Italy, Spain, Finland, Baltic countries, Central Europe, Eastern Europe, Russia, Latin America, Turkey, Iran, and Iraq had a lower risk of VT and/or PE than Swedish-born individuals. The lower risk of VT and/or PE in some first-generation immigrant groups was not replicated in the second generation. However, in certain second-generation immigrant groups, the risk of VT/PE was similar to that in the corresponding parental groups. Conclusions Country of birth affects the risk of VT and PE in several immigrant groups. Our study indicates that ethnicity-related inherited and acquired venous thromboembolism risk factors play a role in the aetiology of venous thromboembolism. Ethnic differences in thromboembolism risk even exist in Caucasian European populations, and may thus be important to consider in genetic studies.

Associations of the β-fibrinogen Hae III and factor XIII Val34Leu gene variants with venous thrombosis

Introduction The factor XIII Val34Leu (100 G → T) and β-fibrinogen Hae III (− 455 G → A) gene variants have been associated with reduced risk of venous thrombosis, but not in all studies. Methods We investigated the associations of these polymorphisms with risk of venous thrombosis in a prospective, population-based study of 21,680 men and women aged 45–100 years at enrollment. Factor XIII 100 G/T and β-fibrinogen − 455 G/A were analyzed on stored DNA from 511 thrombosis cases and 1028 control subjects without thrombosis during follow up. Results The β-fibrinogen A allele was present in 24.4% of cases and 32.3% of controls. Compared to GG subjects, the age, race, and sex adjusted odds ratio (OR) of venous thrombosis was 0.77 (95% CI 0.59–0.99) for GA subjects, and 0.60 (95% CI 0.31–1.16) for AA subjects. The adjusted OR of thrombosis associated with factor XIII 100 G/T was 1.01 (95% CI 0.81–1.26) for GT subjects and 0.45 (95% CI 0.44–1.19) for TT subjects, compared to GG. For both genotypes, ORs of thrombosis were similar in whites and non-whites, although there were no non-white fibrinogen AA cases. β-fibrinogen − 455 GA or AA attenuated the thrombosis risk associated with obesity (from 2.14 to 1.25) and factor V Leiden (from 3.89 to 2.36). Conclusions β-fibrinogen − 455 G/A, but not factor XIII 100 G/T, was associated with a lower risk of venous thrombosis in this general population sample. β-fibrinogen − 455 A may attenuate the increased thrombosis risk associated with obesity or factor V Leiden.

HMG CoA reductase inhibitors and the risk of venous thrombosis among postmenopausal women

HMG CoA reductase inhibitors and the risk of venous thrombosis among postmenopausal women

Polymorphisms in the 5' regulatory region of the tissue factor gene and the risk of myocardial infarction and venous thromboembolism: the ECTIM and PATHROS studies. Etude Cas-Témoins de l'Infarctus du Myocarde. Paris Thrombosis case-control Study.

Tissue factor (TF) is a transmembrane protein considered to be responsible for the initiation of coagulation. TF gene expression may be induced in monocytes and endothelial cells and is present in atherosclerotic plaque to initiate thrombus formation. To investigate whether individual differences in TF gene expression could predispose subjects to thrombosis, we sequenced the 5' domain of the gene up to nucleotide 2732 and found 6 different polymorphisms: 4 of them were completely concordant and defined 2 haplotypes with similar frequencies, designated as 1208 D and 1208 I. Genotyping of patients with myocardial infarction in a case-control study involving 2354 subjects showed no association between the polymorphisms and nonfatal coronary thrombosis. In another study involving 255 patients with venous thromboembolism and 1204 controls, allele D was less common in the cases (P=0.022). The odds ratio associated with the presence of at least 1 D allele was 0.72 (P=0. 031). Comparison of subgroups of control subjects who were homozygous for the D or I allele demonstrated a lower plasma TF concentration in DD homozygotes. These results indicate that the TF gene promoter exists in 2 major forms differing at 4 sites. The 1208 D haplotype is not associated with coronary thrombosis but is associated with reduced plasma TF levels and a lower risk of venous thrombosis.