Venous thrombosis: understanding the paradoxes of recurrence.

The decision to continue anticoagulant treatment in patients with a first venous thrombosis after the initial treatment period has strong, life-long implications. Both the risk of recurrence when treatment is stopped and the risk of bleeding when it is continued are high and will persist over a patient's lifetime. For clinicians, rational strategies to stratify their patients into levels of risk of recurrence are limited. To support in the decision to continue or not, it is of the utmost importance to understand why some people develop a second event and others do not and how these people can be identified. This is not easy as, contrary to intuition, the risk profile of a recurrent event is entirely different from that of a first: Some genetic factors that have a major effect on first thrombosis only marginally predict recurrence, while, for instance, the opposite is true for male sex. These paradoxes can be explained when we understand etiology of a first event, how rates for first and second event cannot be directly compared, and how fixed risk factors cannot be predictors, while factors that are not causes can yet be predictors. Integrating all knowledge and combining the best predicting variables will ultimately lead to ways to estimate an individual's recurrence risk and hence to decide on optimal further treatment.