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Cerebral venous thrombosis (CVT) predominantly affects young to middle-aged women. Scarce data exist regarding the long-term prognosis. We examined the clinical course of patients with CVT overall and according to their age and sex. Using Danish registries, we identified all patients with a first-time primary inpatient diagnosis of CVT from 1996-2018 (N = 653; median age, 41 years; 67% women) and individuals from the general population matched for age, sex, and calendar year (N = 65 300). Patients with CVT were at an increased risk of venous thromboembolism (VTE) at other sites, ischemic stroke, major bleeding, and mortality. For both sexes, the increased risks of VTE at other sites were most prominent among younger patients (18-54 years), whereas the increased risks of ischemic stroke, major bleeding, and mortality were most prominent among older patients (≥55 years). Among young women, the 10-year risks of VTE at other sites for patients with CVT compared with members of the matched cohort were 2.2% vs 0.4% (risk difference, 1.8%; 95% confidence interval [CI], 0.0-3.6). Among older women, compared with members of the matched cohort, the 10-year risks were 12.8% vs 3.1% (risk difference, 9.7%; 95% CI, 1.6-17.9) for ischemic stroke, 11.1% vs 4.6% (risk difference, 6.5%; 95% CI, -1.0 to 14.1) for major bleeding, and 43.1% vs 26.7% (risk difference, 16.4%; 95% CI, 3.7-29.1) for all-cause mortality. The risk of myocardial infarction was not elevated. Clinicians should be aware of the importance of age and sex heterogeneity in the prognosis of CVT., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Intuitively, researchers do not include subjects who do not have the opportunity to be exposed, such as men in studies on oral contraceptives (OCs). We aimed to explore in which situations it is nevertheless beneficial to do so. We considered the effect of including men in case-control analyses of 8 different hypothetical data sets on the effect of OC use and venous thrombosis. In all scenarios, OC use was the exposure of interest, sex the factor that determined exposure opportunity, and air travel another risk factor. In some of these scenarios, sex and air travel were included as confounders or effect modifiers. Logistic regression was used to estimate odds ratios. Standard errors of the estimated log odds ratios, including and excluding men, were compared. We also studied the effect of including men using data from 1999-2004 from a case-control study on risk factors for venous thrombosis, conducted in the Netherlands. In all hypothetical examples, and in the real-data study, addition of men to the analysis yielded the same odds ratios when correctly adjusting for confounding. Moreover, use of additional subjects often led to more precise estimates. We suggest that subjects who do not have the opportunity to be exposed should not routinely be excluded from epidemiologic studies., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: A potentially useful role for instrumental variable (IV) analysis may be as a complementary analysis to assess the presence of confounding when studying adverse drug effects. There has been discussion on whether the observed increased risk of venous thromboembolism (VTE) for third-generation oral contraceptives versus second-generation oral contraceptives could be (partially) attributed to confounding. We investigated how prescribing preference IV estimates compare with conventional estimates., Methods: Women in the Clinical Practice Research Database who started a second-generation or third-generation oral contraceptive from 1989 to 2013 were included. Ordinary least squares and two-stage least squares regression were used to estimate risk differences in VTE. Cox regression and IV for Cox proportional hazards regression were used to calculate hazard ratios (HR). The instrument used was the proportion of prescriptions for third-generation oral contraceptives by the general practitioner in the year preceding the current prescription., Results: All analyses pointed in the direction of an increased VTE risk for third-generation oral contraceptives. The adjusted HR from the conventional Cox regression was 1.62 (95% confidence interval 1.16-2.27) and the fully adjusted HR from the IV Cox regression was 3.45 (95% confidence interval; 0.97-11.7), showing a larger risk and wider confidence intervals in the IV analysis., Conclusions: The similarity in direction of results from the IV analyses and conventional analyses suggests that major confounding is unlikely. IV analysis can be a useful complementary analysis to assess the presence of confounding in studies of adverse drug effects in very large databases., (Copyright © 2016 John Wiley & Sons, Ltd.)

Recently, it has become apparent that superficial vein thrombosis (SVT) can have serious complications. However, the magnitude of the risk of subsequent deep venous and arterial thrombotic events remains unknown. We examined this in a nationwide population-based setting during a period when SVT was not treated routinely with anticoagulants. The Danish National Registry of Patients, covering all Danish hospitals, was used to identify 10 973 patients with a first-time diagnosis of SVT between 1980 and 2012. A comparison cohort of 515 067 subjects, matched by age, gender, and calendar year, was selected from the general Danish population. Outcomes were venous thromboembolism, acute myocardial infarction, ischemic stroke, and death. During median follow-up of 7 years, the incidence rate of venous thromboembolism was 18.0/1000 person-years (95% confidence interval [CI], 17.2-18.9). The highest risk occurred in the first 3 months (3.4%; 95% CI, 3.0-3.7). Compared with the general population, the hazard ratio was 71.4 (95% CI, 60.2-84.7) in this period, steadily decreasing to 5.1 (95% CI 4.6-5.5), 5 years after the SVT. The hazard ratios for acute myocardial infarction, stroke, and death were 1.2 (95% CI, 1.1-1.3), 1.3 (95% CI, 1.2-1.4), and 1.3 (95% CI, 1.2-1.3), respectively, with the highest risk also shortly after SVT. These data indicate the prognostic importance of SVT and may form the basis for clinical decision-making regarding anticoagulation., (© 2015 by The American Society of Hematology.)

Venous thrombosis and arterial thrombosis are traditionally regarded as two different diseases with respect to pathophysiology, epidemiology, and treatment strategies. Research findings of the past few years suggest that this categorical distinction may be too strict. However, whether the described relationship between venous and arterial thrombosis is real or a result of other factors such as confounding, chance, or bias is still unclear. In this review, we discuss the current literature while using causal diagrams to better understand possible causal relations between cardiovascular risk factors, atherosclerosis, arterial thrombosis, and venous thrombosis. Furthermore, we propose study designs to investigate the causal link between venous and arterial thrombosis. In addition, we comment on the effect of statin use on the occurrence of both arterial and venous thrombosis. The possible clinical implications of these findings are discussed., (© Thieme Medical Publishers.)

Context: Data on the recurrence rate of venous thrombotic events and the effect of several risk factors, including thrombophilia, remain controversial. The potential benefit of screening for thrombophilia with respect to prophylactic strategies and duration of anticoagulant treatment is not yet known., Objectives: To estimate the recurrence rate of thrombotic events in patients after a first thrombotic event and its determinants, including thrombophilic abnormalities., Design, Setting, and Patients: Prospective follow-up study of 474 consecutive patients aged 18 to 70 years without a known malignancy treated for a first objectively confirmed thrombotic event at anticoagulation clinics in the Netherlands. The Leiden Thrombophilia Study (LETS) was conducted from 1988 through 1992 and patients were followed up through 2000., Main Outcome Measures: Recurrent thrombotic event based on thrombophilic risk factors, sex, type of initial thrombotic event (idiopathic or provoked), oral contraceptive use, elevated levels of factors VIII, IX, XI, fibrinogen, homocysteine, and anticoagulant deficiencies., Results: A total of 474 patients were followed up for mean (SD) of 7.3 (2.7) years and complete follow-up was achieved in 447 (94%). Recurrence of thrombotic events occurred in 90 patients during a total of 3477 patient-years. The rate of thrombotic event recurrence was 25.9 per 1000 patient-years (95% confidence interval [CI], 20.8-31.8 per 1000 patient-years). The incidence rate of recurrence was highest during the first 2 years (31.9 per 1000 patient-years; 95% CI, 20.3-43.5 per 1000 patient-years). The risk of thrombotic event recurrence was 2.7 times (95% CI, 1.8-4.2 times) higher in men than in women. Patients whose initial thrombotic event was idiopathic had a higher risk of a thrombotic event recurrence than patients whose initial event was provoked (hazard ratio [HR], 1.9; 95% CI, 1.2-2.9). Women who used oral contraceptives during follow-up had a higher thrombotic event recurrence rate (28.0 per 1000 patient-years; 95% CI, 15.9-49.4 per 1000 patient-years) than those who did not (12.9 per 1000 patient-years; 95% CI, 7.9-21.2 per 1000 patient-years). Recurrence risks of a thrombotic event by laboratory abnormality ranged from an HR of 0.6 (95% CI, 0.3-1.1) in patients with elevated levels of factor XI to an HR of 1.8 (95% CI, 0.9-3.7) for patients with anticoagulant deficiencies., Conclusions: Prothrombotic abnormalities do not appear to play an important role in the risk of a recurrent thrombotic event. Testing for prothrombotic defects has little consequence with respect to prophylactic strategies. Clinical factors are probably more important than laboratory abnormalities in determining the duration of anticoagulation therapy.

In gynaecology, women are exposed to sex steroids when using oral contraceptives, hormone replacement therapy or when undergoing in vitro fertilization treatment and ovulation induction. Oral contraceptives and the use of hormone replacement therapy increase the risk of venous thrombosis. The risk is highest in the first year of use and higher among women with clotting defects. Women taking third-generation oral contraceptives have an almost twofold increased risk of venous thrombosis compared with those taking second-generation oral contraceptives. Inherited clotting defects, which are themselves risk factors of venous thrombosis, (e.g. factor V Leiden mutation, deficiency of protein C, protein S or antithrombin, high plasma levels of factor VIII, and prothrombin mutation) appear synergistically increase the risk of venous thrombosis caused by oral contraceptives. Recent studies also point to an interaction between hormone replacement therapy and coagulation defects in causing venous thrombosis. Emerging studies show that in vitro fertilization treatment and ovulation induction are also risk factors for venous thrombosis; the role of coagulation defects in this association is not yet clear.

Background: In an autopsy series, 10 out of 27 deaths in which 'idiopathic' pulmonary emboli were discerned as the sole cause of death had occurred in psychiatric patients.Aims: To investigate whether antipsychotic medication is a risk factor for venous thrombosis.Method: A description of the 10 psychiatric patients was obtained from the pulmonary emboli autopsy reports. We carried out a brief historic overview of the literature. We re-analysed data from the Leiden Thrombophilia Study (LETS), a case-control study on patients with venous thrombosis.Results: In the autopsy reports, five out of 10 psychiatric patients with fatal pulmonary embolism had confirmed use of antipsychotic drugs. After the application of chlorpromazine and its analogues a higher incidence of venous thrombosis in psychiatric patients was described in the German literature between 1953 and 1977. In the re-analysis of the LETS case-control study, four patients used antipsychotic drugs versus none in the control group. Recent epidemiological studies of good methodological quality have confirmed these findings.Conclusions: Venous thrombosis appears to be associated with the use of antipsychotic drugs in psychiatric patients. [ABSTRACT FROM AUTHOR]

Investigates whether the occurrence of venous thrombosis in young women who use oral contraceptives might be explained by the factor V Leiden mutation. Mutation's production of resistance to activated protein C; Mutation's enhancement of susceptibility to thrombosis; Risk of thrombosis among carriers and non-carriers.

Reports on developments in the understanding of venous thrombosis resulting from oral contraceptive use. Risks associated with low-dose oral contraceptives; Possible effect of progestin on increased risk of venous thrombosis; The effect of progestins in combined preparations; Susceptibility to prothrombotic states; Mechanisms of venous thrombosis induced by oral contraceptives.

Presents a commentary on three studies of venous thrombosis. Risk of venous thromboembolism with estrogen-only and with combined estrogen-progestagen hormone-replacement therapy; Why the findings of the studies are important; Progestagens in replacement therapy; Hormone replacement; Venous thrombosis associated with oral contraceptives in younger women; The risk factors for venous thromboembolism.