Risk of recurrent venous thromboembolism in patients with HIV infection:A nationwide cohort study

Background Multiple 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 findings PWH 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. Conclusions Overall, 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 summary Why 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 Environmenta

Evidence-based approach to thrombophilia testing

Thrombophilia can be identified in about half of all patients presenting with VTE. Testing has increased tremendously for various indications, but whether the results of such tests help in the clinical management of patients has not been settled. I use evidence from observational studies to conclude that testing for hereditary thrombophilia generally does not alter the clinical management of patients with VTE, with occasional exceptions for women at fertile age. Because testing for thrombophilia only serves limited purpose this should not be performed on a routine basis

Influence of World Thrombosis Day on digital information seeking on venous thrombosis: a Google Trends study

Essentials In 2014, World Thrombosis Day (WTD) was initiated to increase global awareness of thrombosis. Google Trends can be used freely to monitor digital information seeking behavior. We used Google Trends data to assess the impact of WTD on internet searches on venous thrombosis. The WTD period was associated with more searches on thrombosis compared to control periods. Background World Thrombosis Day (WTD) was launched in 2014 and is to be held every year to increase global awareness of venous thrombosis. Measuring the impact of health awareness days is challenging; however, use of internet-based data seems promising. Methods Google Trends data were used to quantify digital searches for 'venous thrombosis' worldwide and 'trombose' in the Netherlands. The relative search volume (RSV), which is the proportion of the term of interest amongst all Google searches for a specific region and timeframe was used. Mean differences for 4 weeks surrounding WTD (period of interest) and the remaining weeks of the year (control period) were estimated with 95% confidence intervals (95% CI). This was done for 2014, 2015 and 2009-2013 (control years). Results and discussion Mean differences in RSV for worldwide searches were 2.9 (95% CI, -8.2, 14.1) in 2014 and 10.5 (95% CI, 0.4, 20.5) in 2015. These figures were 15.3 (95% CI, 4.7, 25.8) and 15.9 (95% CI, 7.8, 24.1) for the Netherlands, respectively. Relatively, this corresponds to an increase in RSV of 3.9% and 13.9% for 2014 and 2015 worldwide and a 21.9% and 23.3% increase for 2014 and 2015 in the Netherlands. There was one control year with an increase in RSV in the WTD period. Conclusion In 2014 and 2015 WTD was associated with an increase in digital information seeking on venous thrombosis worldwide. This association was more pronounced in 2015 than in 201

Hematologic variables and venous thrombosis: red cell distribution width and blood monocyte count are associated with an increased risk

Thrombosis and Hemostasi