Background Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to... Show moreBackground Statins are a potential treatment for venous thromboembolism (VTE) prophylaxis complementary to conventional anticoagulants without associated bleeding complications. This study aimed to compare pro-thrombotic activities of different classes of lipid-lowering drugs in an active comparator design and determine whether there is a relation between statin versus fibrate/niacin use and pro-coagulant factor outcomes. Methods This is a cross-sectional analysis of participants from the Netherlands Epidemiology of Obesity study using any class of lipid-lowering drugs, including any types of statins, niacin, and fibrates. We performed linear regression analyses to determine fibrinogen, factor (F) VIII, FIX, and FXI activity in statins versus fibrate/niacin users and adjusted for age, sex, tobacco smoking, body mass index (BMI), hypertension, diabetes, and prevalent cardiovascular disease. Results Among 1043 participants, the mean age was 58.4 +/- 5.2 years, 61% were men, and the mean BMI was 31.3 +/- 4.5 kg/m(2). Clinical characteristics were balanced between statin and fibrate/niacin users. Statin users had lower mean FXI (18.3 IU/dL, 95% confidence interval (CI) 9.4 to 27.3) levels compared to fibrate/niacin users. The level of FVIII (15.8 IU/dL, 95% CI - 0.003 to 31.6), and FIX (11.3 IU/dL, 95% CI - 0.4 to 23.2) were lower in statin users than fibrate/niacin users with marginal statistical significance. Conclusion Current statin use was associated with lower plasma levels of FXI than fibrate/niacin use. The effects on coagulation factors may, in part, explain the benefit of statin therapy rendered in primary and secondary prevention of VTE. Show less
Zielinski, G.D.; Rein, N. van; Teichert, M.; Klok, F.A.; Rosendaal, F.R.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2021
Background Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials.Aims To assess adherence to DOACs in atrial... Show moreBackground Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials.Aims To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence.Methods Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) >= 80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up.Results A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC >= 80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age <= 60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC >= 80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year.Conclusions Non-adherence to DOACs was associated with age <= 60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence. Show less
Glucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to... Show moreGlucocorticoid treatment increases venous thromboembolism (VTE) risk. Whether this is due to the medication or the underlying disease, or affects the risk of VTE recurrence, has been difficult to determine. The aim of our present study was to quantify the risk for first and recurrent VTE associated with oral glucocorticoids use, considering the underlying disease. A total of 2547 patients with VTE from the Multiple Environmental and Genetic Assessment of Risk Factors for Venous Thrombosis (MEGA) study were linked to the Dutch Pharmaceutical Statistics register. The risk of first VTE during periods of exposure with oral glucocorticoids was estimated by the self-controlled case series method and that of recurrent VTE was examined in a cohort design. The incidence rate ratio (IRR) of first VTE in the period of glucocorticoid treatment was 3 center dot 51 [95% confidence interval (CI) 2 center dot 55-4 center dot 80]. This IRR was 2 center dot 53 (95% CI 1 center dot 10-5 center dot 72) in the week before treatment started, 5 center dot 28 (95% CI 2 center dot 89-9 center dot 53) in the first 7 days of treatment, remained elevated afterwards and decreased to 1 center dot 55 (95% CI 0 center dot 85-3 center dot 12) after 6 months, as compared to unexposed periods. The hazard ratio for recurrence was 2 center dot 72 (95% CI 1 center dot 64-4 center dot 78) in treatment periods as compared with no treatment. The increased risk of VTE associated with oral glucocorticoid treatment is due to a combined effect of the treatment and the underlying disease, remaining high during the first months of prescription. Show less
Background: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there... Show moreBackground: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients. In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped.Methods: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status.Findings: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients.Interpretation: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Background: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there... Show moreBackground: Short-term follow-up of COVID-19 patients reveals pulmonary dysfunction, myocardial damage and severe psychological distress. Little is known of the burden of these sequelae, and there are no clear recommendations for follow-up of COVID-19 patients. In this multi-disciplinary evaluation, cardiopulmonary function and psychological impairment after hospitalization for COVID-19 are mapped.Methods: We evaluated patients at our outpatient clinic 6 weeks after discharge. Cardiopulmonary function was measured by echocardiography, 24-hours ECG monitoring and pulmonary function testing. Psychological adjustment was measured using questionnaires and semi-structured clinical interviews. A comparison was made between patients admitted to the general ward and Intensive care unit (ICU), and between patients with a high versus low functional status.Findings: Eighty-one patients were included of whom 34 (41%) had been admitted to the ICU. New York Heart Association class II-III was present in 62% of the patients. Left ventricular function was normal in 78% of patients. ICU patients had a lower diffusion capacity (mean difference 12,5% P = 0.01), lower forced expiratory volume in one second and forced vital capacity (mean difference 14.9%; P<0.001; 15.4%; P<0.001; respectively). Risk of depression, anxiety and PTSD were 17%, 5% and 10% respectively and similar for both ICU and non-ICU patients.Interpretation: Overall, most patients suffered from functional limitations. Dyspnea on exertion was most frequently reported, possibly related to decreased DLCOc. This could be caused by pulmonary fibrosis, which should be investigated in long-term follow-up. In addition, mechanical ventilation, deconditioning, or pulmonary embolism may play an important role. (C) 2021 The Author(s). Published by Elsevier Ltd. Show less
Background: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels... Show moreBackground: Von Willebrand factor (VWF) levels are regulated by genetic and acquired factors. The acquired factors are mostly related to age and could be mediators of the age effect on VWF levels.Objectives: To disentangle the role of genetic (sex, blood group) and acquired factors (comorbidities, body mass index, reduced kidney function, hormone use, and inflammation) in regulating von Willebrand factor antigen (VWF:Ag) and factor VIII activity (FVIII:C) levels in the normal population.Methods: Analysis were performed in a large population sample (2923 individuals) from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA study), after exclusion of individuals with active cancer and women who were pregnant or within nine months postpartum. The increase of VWF:Ag and FVIII:C with age was evaluated by linear regression after the age of 40 years. Analyses were adjusted for acquired factors and stratified for sex and blood group.Results: VWF:Ag and FVIII:C increased with age: increase per decade of age for VWF:Ag 18 IU/dL (95%CI 15-20) and for FVIII:C 12 IU/dL (95%CI 10-14). After adjustment for acquired factors, the increase per decade was 13 IU/dL (95%CI 10-16) for VWF:Ag and 9 IU/dL (95%CI 6-11) for FVIII:C. The stratified analysis for blood group showed higher increase in the non-O group, but these differences were annulled after adjustment for acquired factors.Conclusions: VWF:Ag and FVIII:C increase with age. Carriers of blood group non-O present a steeper increase of VWF:Ag and FVIII:C with age, that is mediated by acquired factors. Show less
Morelli, V.M.; Mutsert, R. de; Roos, A. de; Lamb, H.J.; Vlieg, A.V.; Bos, M.H.A.; ... ; Cannegieter, S.C. 2020
Objective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate... Show moreObjective:Whether hepatic triglyceride content (HTGC) contributes to hypercoagulability beyond total body fat (TBF) and visceral adipose tissue (VAT) is unclear. We, therefore, aimed to investigate the association between HTGC and coagulation factors (F)I (fibrinogen), VIII, IX, and XI while adjusting for TBF and VAT.Approach and Results:In this cross-sectional analysis of the NEO study (Netherlands Epidemiology of Obesity; n=6671), a random subset of participants underwent magnetic resonance imaging and magnetic resonance spectroscopy to assess VAT and HTGC (n=2580). We excluded participants without complete imaging and coagulation assessment, and with history of liver disease, venous thrombosis, or on anticoagulation. Mean differences in coagulation factor levels across HTGC quartiles were estimated by linear regression adjusted for age, sex, ethnicity, education, alcohol intake, physical activity, smoking, estrogen, and menopause, in addition to TBF and VAT. Among the 1946 participants included, median HTGC was 2.66% (interquartile range: 1.34%-6.27%). Coagulation factor levels increased dose-dependently across HTGC quartiles. Mean differences between the fourth and first quartiles were 14.7 mg/dL (95% CI, 2.1-27.2) for fibrinogen, 6.7 IU/dL (95% CI, 0.5-12.9) for FVIII, 26.1 IU/dL (95% CI, 22.4-29.8) for FIX, and 8.6 IU/dL (95% CI, 4.6-12.6) for FXI. With further adjustment for TBF and VAT, the dose-response association of HTGC with FIX persisted, whereas associations with other factors disappeared.Conclusions:HTGC was associated with various coagulation factors, of which FIX remained associated with HTGC after adjustment for TBF and VAT. HTGC might contribute to venous thrombosis risk beyond total body and visceral fat through FIX levels. Show less
Direct oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are... Show moreDirect oral anticoagulants (DOACs) are increasingly used for treatment and prevention of thromboembolic diseases, used in fixed dose regimens. Although their safety and efficacy profiles are considered optimal, clinical events still occur. Given that anticoagulation treatment is a delicate balance between clotting and bleeding, it is possible that an optimal target spot exists where the effect of anticoagulation achieves both the lowest possible risk of bleeding and thrombosis. Other currently available anticoagulants (ie, vitamin K antagonists and heparins) provide important clues for this. If such a target spot exists, tailored DOAC therapy may further benefit patients. This opinion article summarizes the current available evidence that suggests that such a tailored strategy could work. It also describes research suggestions for conducting studies in patient populations such as patients with extremes of body weight or impaired kidney function to evaluate whether tailored treatment with DOACs could lead to better patient outcomes. Show less
BackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19... Show moreBackgroundTo evaluate the association between crowding and transmission of viral respiratory infectious diseases, we investigated the change in transmission patterns of influenza and COVID-19 before and after a mass gathering event (i.e., carnival) in the Netherlands.MethodsInformation on individual hospitalizations related to the 2017/2018 influenza epidemic were accessed from Statistics Netherlands. The influenza cases were stratified between non-carnival and carnival regions. Distributions of influenza cases were plotted with time and compared between regions. A similar investigation in the early outbreak of COVID-19 was also conducted using open data from the Dutch National Institute for Public Health and the Environment.ResultsBaseline characteristics between non-carnival and carnival regions were broadly similar. There were 13,836 influenza-related hospitalizations in the 2017/2018 influenza epidemic, and carnival fell about 1week before the peak of these hospitalizations. The distributions of new influenza-related hospitalizations per 100,000 inhabitants with time between regions followed the same pattern with a surge of new cases in the carnival region about 1week after carnival, which did not occur in the non-carnival region. The increase of new cases for COVID-19 in the carnival region exceeded that in the non-carnival region about 1week after the first case was reported, but these results warrant caution as for COVID-19 there were no cases reported before the carnival and social measures were introduced shortly after carnival.ConclusionIn this study, a mass gathering event (carnival) was associated with aggravating the spread of viral respiratory infectious diseases. Show less
Venous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an... Show moreVenous thromboembolism (VTE) is a chronic disease. Strategies to assess groups at a high risk of recurrence are needed. We reported that patients without prior risk situation for VTE had an incidence rate ratio (IRR) three times higher when compared with those with this history. The aim of this study was to re-evaluate the cohort, with a longer follow-up and evaluated the association between the absence of a prior risk situation for VTE with an increased risk for recurrence. A total of 289 patients with a previous VTE were followed for 116 months. Patients were advised to attend the outpatients' clinic in case of suspected VTE recurrence. Incidence rates of recurrent thrombotic events were calculated as the number of events over the accumulated observation time. Recurrent VTE occurred in 52 (18%) patients. Patients with a provoked first event and positive prior risk situations for VTE had an incidence rate for recurrence of 1.2 [95% confidence interval (95% CI), 0.7-1.9] per 100 patient-years. The IRR of this subgroup compared with patients with a provoked event without prior risk situations for VTE was 0.9 (95% CI 0.4-2.4). IRR was 2.5 (95% CI, 1.3-4.9) in patients with an unprovoked event and positive prior risk situations and 5.9 (95% CI, 32.8-12.5) in patients with an unprovoked event and no prior risk situations compared with patients with a provoked event without other prior risk situations for VTE. Exposure to prior risk situations for VTE was a protective factor among those patients whose first VTE event was unprovoked. Show less
Over the past decade opioid use has risen globally. The causes and consequences of this increase, especially in Europe, are poorly understood. We conducted a population-based cohort study using... Show moreOver the past decade opioid use has risen globally. The causes and consequences of this increase, especially in Europe, are poorly understood. We conducted a population-based cohort study using national statistics on analgesics prescriptions, opioid poisoning hospital admissions and deaths in the Netherlands from 2013 to 2017. Pain prevalence and severity was determined by using results of 2014-2017 Health Interview Surveys. Between 2013 and 2017 the proportion of residents receiving opioid prescription rose from 4.9% to 6.0%, and the proportion of those receiving NSAIDs decreased from 15.5% to 13.7%. Self-reported pain prevalence and severity remained constant, as 44.7% of 5,119 respondents reported no pain-impeded activities-of-daily-living in 2014 (aRR, 1.00 [95% CI, 0.95-1.06] in 2017 vs 2014). Over the observation period, the incidence of opioid poisoning hospitalization and death increased from 8.6 to 12.9 per 100,000 inhabitants. The incidence of severe outcomes related to opioid use increased, as 3.9% of 1,343 hospitalized for opioid poisoning died in 2013 and 4.6% of 2,055 in 2017. We demonstrated that NSAIDs prescription decreased and opioid prescription increased in the Netherlands since 2013, without an increase in pain prevalence and severity. Consequently, the incidence of severe outcomes related to opioids increased. Show less
Toorop, M.M.A.; Rein, N. van; Cannegieter, S.C.; Meer, F.J.M. van der; Reitsma, P.H.; Lijfering, W.M.; Bos, M.H.A. 2020
Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while... Show moreBackground Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case-cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1-3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (>= 4) in the presence of high (>= 70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1-12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR. Show less
Toorop, M.M.A.; Rein, N. van; Nierman, M.C.; Vermaas, H.W.; Huisman, M.V.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2020
Background Since direct oral anticoagulants (DOACs) have been introduced for treatment and prevention of thromboembolic diseases, patients on vitamin K antagonists (VKA) have to decide whether to... Show moreBackground Since direct oral anticoagulants (DOACs) have been introduced for treatment and prevention of thromboembolic diseases, patients on vitamin K antagonists (VKA) have to decide whether to remain on VKA or switch to DOAC. The goal of this study was to evaluate treatment satisfaction, preferences, and concerns among those who already have switched from VKA to DOAC.Methods A questionnaire was sent to 2920 former patients of three anticoagulation clinics in the Netherlands, who switched from VKA to DOAC (2016-2017). Questions concerned demographics, treatment satisfaction, concerns, perspectives on antidotes, and monitoring. To identify predictors for being concerned about adverse events, logistic regression was used to estimate crude- and adjusted (age and sex) odds ratios (OR) and 95% confidence intervals (95% CI).Results One thousand, three hundred ninety-nine questionnaires (response rate 48%) were used for analysis. DOAC treatment satisfaction was high (mean 8.8 of a maximum 10-point score). A quarter of patients expressed concerns about adverse events. Predictors for being concerned were age < 60 years (vs age > 75 years, OR 4.1, 95% CI 2.6-6.4), female sex (OR 1.3, 95% CI 1.0-1.6), and high education (OR 1.6, 95% CI 1.2-2.2). Fifty-nine percent of all patients indicated antidote availability as important, 73% would be willing to participate in DOAC monitoring.Conclusions DOAC treatment satisfaction was high. A substantial number of patients expressed concerns about adverse events, especially women, patients aged < 60 years, or highly educated patients. Our findings among patients who already had switched to DOAC may assist in the process of shared decision-making when switching a patient from VKA to DOAC is considered. Show less
BackgroundMultiple studies have described a higher incidence of venous thromboembolism (VTE) in people living with an HIV infection (PWH). However, data on the risk of recurrent VTE in this... Show moreBackgroundMultiple studies have described a higher incidence of venous thromboembolism (VTE) in people living with an HIV infection (PWH). However, data on the risk of recurrent VTE in this population are lacking, although this question is more important for clinical practice. This study aims to estimate the risk of recurrent VTE in PWH compared to controls and to identify risk factors for recurrence within this population.Methods and findingsPWH with a first VTE were derived from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort (2003-2015), a nationwide ongoing cohort following up PWH in care in the Netherlands. Uninfected controls were derived from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) follow-up study (19992003), a cohort of patients with a first VTE who initially participated in a case-control study in the Netherlands who were followed up for recurrent VTE. Selection was limited to persons with an index VTE suffering from deep vein thrombosis in the lower limbs and/or pulmonary embolism (PE). Participants were followed from withdrawal of anticoagulation to VTE recurrence, loss to follow-up, death, or end of study. We estimated incidence rates, cumulative incidence (accounting for competing risk of death) and hazard ratios (HRs) using Cox proportional hazards regression, adjusting for age, sex, and whether the index event was provoked or unprovoked. When analyzing risk factors among PWH, the main focus of analysis was the role of immune markers (cluster of differentiation 4 [CD4]+ T-cell count).There were 153 PWH (82% men, median 48 years) and 4,005 uninfected controls (45% men, median 49 years) with a first VTE (71% unprovoked in PWH, 34% unprovoked in controls) available for analysis. With 40 VTE recurrences during 774 person-years of follow-up (PYFU) in PWH and 635 VTE recurrences during 20,215 PYFU in controls, the incidence rates were 5.2 and 3.1 per 100 PYFU (HR: 1.70, 95% CI 1.23-2.36, p = 0.003). VTE consistently recurred more frequently per 100 PYFU in PWH in all predefined subgroups of men (5.6 versus 4.8), women (3.6 versus 1.9), and unprovoked (6.0 versus 5.2) or provoked (3.1 versus 2.1) first VTE. After adjustment, the VTE recurrence risk was higher in PWH compared to controls in the first year after anticoagulant discontinuation (HR: 1.67, 95% CI 1.04-2.70, p = 0.03) with higher cumulative incidences in PWH at 1 year (12.5% versus 5.6%) and 5 years (23.4% versus 15.3%) of follow-up. VTE recurred less frequently in PWH who were more immunodeficient at the first VTE, marked by a better CD4+ T-cell recovery on antiretroviral therapy and during anticoagulant therapy for the first VTE (adjusted HR: 0.81 per 100 cells/mm3 increase, 95% CI 0.67-0.97, p = 0.02). Sensitivity analyses addressing potential sources of bias confirmed our principal analyses. The main study limitations are that VTEs were adjudicated differently in the cohorts and that diagnostic practices changed during the 20-year study period.ConclusionsOverall, the risk of recurrent VTE was elevated in PWH compared to controls. Among PWH, recurrence risk appeared to decrease with greater CD4+ T-cell recovery after a first VTE. This is relevant when deciding to (dis)continue anticoagulant therapy in PWH with otherwise unprovoked first VTE.Author summaryWhy was this study done?The HIV pandemic affects approximately 40 million people and causes significant morbidity, including a markedly increased risk of a venous thromboembolism (VTE).The recurrence risk of VTE in people living with HIV (PWH) is unknown, although this risk drives the anticoagulant therapy duration after a first VTE.Our study determined the recurrent VTE risk in PWH compared to uninfected controls.What did the researchers do and find?We performed an observational cohort study using data from the national ATHENA PWH cohort (2003-2015) in the Netherlands and the Dutch Multiple Environmental Show less
It is not known whether the synergistic effect of genetic markers, increasing the risk of venous thrombosis (VT), and combined oral contraceptives (COC) use varies between different types of... Show moreIt is not known whether the synergistic effect of genetic markers, increasing the risk of venous thrombosis (VT), and combined oral contraceptives (COC) use varies between different types of progestogens in these preparations. We investigated the joint effect of genetic risk factor, that is, F5 rs6025, F2 rs1799963, and FGG rs2066865 mutations, and different progestogens on the risk of VT. The constrained maximum likelihood estimation (CMLE) method was used to calculate joint effects, expressed as odds ratio (OR) with 95% confidence intervals [CI]. As the dose of estrogen is known to be a risk factor for VT, analyses were restricted to COC with 30 mu g estrogen and each progestogen. Overall, the joint effect of COC and genetic variants was lowest for COC containing the progestogen levonorgestrel, albeit CIs were wide. The OR (95% CI) of the four different analyses (i.e. joint effect with F5 rs6025, F2 rs1799963, F5 rs6025 or F2 rs1799963 and FGG rs2066865) ranged between 7 center dot 4 (5 center dot 4-10 center dot 2) and 24 center dot 8 (12 center dot 3-50 center dot 0) for levonorgestrel. For gestodene the joint effect ranged between 11 center dot 7 (7 center dot 2-19 center dot 1) and 30 center dot 9 (10 center dot 6-89 center dot 9). Desogestrel and cyproterone acetate had the highest risk estimates: 14 center dot 6 (9 center dot 7-21 center dot 9) and 32 center dot 6 (13 center dot 2-80 center dot 6) and 15 center dot 5 (9 center dot 7-24 center dot 9) and 44 center dot 4 (16 center dot 9-116 center dot 3) respectively. In women with inherited thrombophilia, COC containing levonorgestrel were associated with the lowest risk of VT, albeit the CIs were wide. Show less
We conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce... Show moreWe conducted a study to assess the effect of rosuvastatin use on fibrinolysis in patients with previous venous thromboembolism (VTE). This was a post hoc analysis within the STAtins Reduce Thrombophilia (START) study (NCT01613794). Plasma fibrinolytic potential, fibrinogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) were measured before and after four weeks of rosuvastatin or no treatment in participants with prior confirmed VTE, after ending anticoagulant therapy. In the non-rosuvastatin group (n = 121), plasma fibrinolytic potential and individual fibrinolysis parameters did not change at the end of the study versus the baseline, whereas in the rosuvastatin group (n = 126), plasma fibrinolytic potential increased: the mean clot lysis time decreased by 8 center dot 75 min (95% CI -13 center dot 8 to -3 center dot 72), and plasmin inhibitor levels and TAFI activity were lower at the end of the study (-0 center dot 05 U/ml; 95% CI -0 center dot 07 to -0 center dot 02 and -4 center dot 77%; 95% CI -6 center dot 81 to -2 center dot 73, respectively). PAI-1 levels did not change and fibrinogen levels were 0 center dot 17 g/l (95% CI 0 center dot 04-0 center dot 29) higher. In participants with prior VTE, rosuvastatin use led to an increased fibrinolytic potential compared with non-statin use. Our findings support the need for further studies on the possible role for statins in the secondary prevention of VTE. Show less
Background: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to... Show moreBackground: The adipocyte-derived hormone leptin has been associated with altered blood coagulation in in vitro studies. However, it is unclear whether this association is relevant in vivo and to what extent this association is influenced by total body fat. Therefore, we aimed to examine the association between serum leptin and blood coagulation while taking total body fat into account in a population-based cohort study.Methods: We performed a cross-sectional analysis with baseline measurements of 5797 participants of the Netherlands Epidemiology of Obesity (NEO) study, a population-based cohort of middle-aged men and women. We examined associations between serum leptin concentration and coagulation factor concentrations and parameters of platelet activation in linear regression analyses. All analyses were adjusted for multiple covariates, including total body fat.Results: In multivariable adjusted analyses a 1 mu g/L higher serum leptin concentration was associated with a 0.22 IU/dL (95% CI: 0.11, 0.32) higher FVIII concentration and a 0.20 IU/dL (95% CI: 0.14, 0.27) higher FIX concentration (3.5 IU/dL FVIII and 3.2 IU/dL FIX per SD leptin). Serum leptin concentration was not associated with FXI, fibrinogen, platelet count, mean platelet volume and platelet distribution width in multivariable adjusted analyses.Discussion: This study showed that serum leptin concentration was associated with higher concentrations of FVIII and FIX in an observational study, which could be clinically relevant. Show less
Toorop, M.M.A.; Rein, N. van; Nierman, M.C.; Vermaas, H.W.; Huisman, M.V.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2020
BackgroundMany patients who used vitamin K antagonists (VKAs) for long-term prevention of thromboembolism are now actively switched to a direct oral anticoagulant (DOAC). Strict adherence to a DOAC... Show moreBackgroundMany patients who used vitamin K antagonists (VKAs) for long-term prevention of thromboembolism are now actively switched to a direct oral anticoagulant (DOAC). Strict adherence to a DOAC is crucial for its success. However, therapy adherence and clinical factors that predict nonadherence are currently not well studied among patients who switched from a VKA to a DOAC.MethodsA questionnaire was developed and sent to 2920 former patients of 3 anticoagulation clinics in the Netherlands, who switched from a VKA to a DOAC between January 2016 and December 2017. Questions concerned demographics, treatment persistence, adherence, and the occurrence of bleeding or thromboembolic events on DOACs. To identify predictors for nonadherence, logistic regression models were used to estimate crude and age/sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 1399 questionnaires (response rate 48%) were used for analysis. DOAC treatment persistence (94%) and adherence (86%) rates were high. Several predictors of nonadherence were identified, including young age (OR, 5.9; 95% CI, 3.6-9.8 for <60 years compared to >75 years), low consultation frequency with a specialist (OR, 1.6; 95% CI, 1.1-2.2), a history of minor bleeding on DOACs (OR, 1.9; 95% CI, 1.3-2.8), and a twice-daily dosing regimen (OR, 1.9; 95% CI, 1.3-2.6).ConclusionsSelf-reported treatment persistence and adherence were high in our study population, and several predictors of nonadherence were identified. Factors that can be influenced (low consult frequency with medical specialist, daily dosing regimen) may be used to improve therapy adherence. Show less
Hypertension during pregnancy and preeclampsia are associated with increased arterial thrombotic risk in later life. Whether these complications are associated with risk of venous thromboembolism ... Show moreHypertension during pregnancy and preeclampsia are associated with increased arterial thrombotic risk in later life. Whether these complications are associated with risk of venous thromboembolism (VTE) on the short term after pregnancy and on the long term, that is, outside pregnancy, is largely unknown. We conducted a nationwide cohort study in women with at least 1 pregnancy and their first VTE risk by linking the Dutch perinatal registry (Perined) to anticoagulation clinics. We used Cox proportional hazard models to estimate hazard ratios (HRs) and corresponding 95% CI for VTE risk in women with hypertension during pregnancy, women with preeclampsia, compared with women with uncomplicated pregnancies (reference). A total of 1 919 918 women were followed for a median of 13.7 (interquartile range, 7.6-19.2) years for a total of 24 531 118 person-years in which 5759 first VTEs occurred; incidence rate: 2.3 (95% CI, 2.3-2.4) per 10 000 person-years. In the first pregnancy and 3-month postpartum period, VTE risk was higher in women with hypertension, HR, 2.0 (95% CI, 1.7-2.4), and highest among women with preeclampsia, HR, 7.8 (95% CI, 5.4-11.3), versus the reference group. On the long term, women with hypertension during pregnancy and preeclampsia had a higher VTE risk: HR, 1.5 (95% CI, 1.4-1.6) and HR, 2.1 (95% CI, 1.8-2.4), respectively, versus the reference group. When excluding events during pregnancy and postpartum, these HRs were 1.4 (95% CI, 1.3-1.5) and 1.6 (95% CI, 1.4-2.0), respectively. In conclusion, hypertension during pregnancy and preeclampsia are associated with an increased VTE risk during pregnancy and postpartum period and in the 13 years after. Show less
