Linda Flinterman and colleagues report on the long-term mortality rate for individuals who have experienced a first venous thrombosis or pulmonary embolism. They describe an ongoing elevated risk of death for individuals who had experienced a venous thrombosis or pulmonary embolism as compared to controls, for up to eight years after the event.

Summary.  Venous thrombosis of the upper extremity is a rare disease. Therefore, not as much is known about risk factors, treatment and the risk of recurrence as for venous thrombosis of the leg. Only central venous catheters and strenuous exercise are commonly known risk factors for an upper extremity venous thrombosis. In this review an overview of the different risk factors, possible treatments and the complications for patients with a venous thrombosis of the upper extremity is given.

AbstractRisk factors for deep-vein thrombosis have been shown not to be always the same as for pulmonary embolism. A well-known example is the factor V Leiden (FVL) paradox: the FVL mutation poses a clearly higher risk for deep-vein thrombosis (DVT) than for pulmonary embolism. We aimed to expand this paradox and therefore present risk estimates for several established risk factors for DVT and pulmonary embolism separately. When such separate risk estimates could not be retrieved from the literature, we calculated these risks in our own data, a large population-based case-control study on venous thrombosis (the MEGA study). Our results showed that the FVL paradox can be broadened (ie, the risk factors oral contraceptive use, pregnancy, puerperium, minor leg injuries, and obesity have an effect comparable with FVL). Furthermore, we found that pulmonary conditions, such as chronic obstructive pulmonary disease, pneumonia, and sickle cell disease, were risk factors with an opposite effect: a higher risk of pulmonary embolism, but little or no effect on DVT. These findings suggest that pulmonary embolism and DVT may not always have the same etiology, and encourage unraveling this phenomenon in further studies.

To cite this article: Timp JF, Lijfering WM, Flinterman LE, van Hylckama Vlieg A, le Cessie S, Rosendaal FR, Cannegieter SC. Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study. J Thromb Haemost 2015; 13: 1823-32.Summary. Background: Prediction of recurrent venous thrombosis remains a challenge in the clinic. Objective: To investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis. Patients/methods: Patients, aged 18-70 years with a first venous thrombosis, were followed from discontinuation of anticoagulant treatment (1999-2010 MEGA follow-up study). The levels of FVIII activity, FVIII antigen and von Willebrand factor (VWF) antigen were measured at least 3 months after cessation of anticoagulant treatment. Results: Of 2242 patients followed for a median of 6.9 years, 343 developed recurrent thrombosis (incidence rate 2.7/100 patient-years; 95% confidence interval [CI] 2.5-3.1). Recurrence rates steadily increased with higher FVIII activity levels, from 1.4 (95% CI 1.0-1.9), 2.3 (95% CI 1.8-2.9), 3.0 (95% CI 2.4-3.7), 3.2 (95% CI 2.5-4.1), 3.9 (95% CI 2.8-5.3) to 5.1 (95% CI 3.8-6.8) per 100 patient-years, for levels ranging from < 100 IU dL À1 to > 200 IU dL À1. Patients in the highest category of FVIII (> 200 IU dL À1 ) had a three-fold higher recurrence rate than patients in the lowest category (≤ 100 IU dL À1 ) (hazard ratio 3.4; 95% CI 2.2-5.3).Results were similar for FVIII antigen and VWF antigen levels, in several sensitivity analyses, and FVIII predicted recurrence rates over a long time period. Within subgroups of patients currently assumed to have low recurrence risks, a high level of FVIII was still predictive for recurrences. Adding FVIII to an existing prediction model (DASH score) improved its predictive value, and, after replacement of D-dimer with FVIII, the model performed equally well, if not better. Conclusions: FVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools.

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.