To test or not to test for thrombophilia after a first episode of venous thromboembolism: a randomized controlled trial to assess effects on clinical outcomes, quality of life, and costs.
07 / 2006 - unknown
The last two decades several hereditary risk factors associated with venous thromboembolism (VTE) have been discovered, often interacting with classical environmental risk factors. In 50-60% of patients with a first episode of VTE such a thrombophilic defect can be detected in blood. This has resulted in widespread testing, also in patients with a first episode, but whether this is effective is unknown. One of the potential implications of detecting thrombophilia would be to prolong the duration of anticoagulant treatment after the acute episode of VTE, as is suggested in for instance the guidelines of the American College of Chest Physicians 2004 (grade 2 level of evidence). Whether this is justified is intensely debated and depends on the balance between potentially beneficial and harmful effects, besides costs. Venous thromboembolism (VTE) consists of deep vein thrombosis and pulmonary embolism (or a combination of both) and is a prevalent disease with an incidence of 2 to 3 per 1000 per year (9), affecting approximately 35,000 patients annually in The Netherlands. The initial treatment consists of (low molecular weight) heparin, followed by anticoagulant treatment with vitamin K antagonists for a period of 3 to 12 months, depending on the clinical setting of the thrombotic episode. Internists, pulmonologists, and general practitioners are involved in the usual care for patients with VTE, as well as surgeons, anesthesiologists and gynaecologists who often have to consider specific prophylactic measures in patients with a history of VTE. This proposal aims to assess the efficiency of thrombophilia testing in patients with a first episode of VTE. The research question is whether testing for thrombophilia in patients with a first episode of VTE and subsequent additional anticoagulant treatment in those in whom thrombophilia is detected is beneficial as compared to no testing and standard duration of therapy in all patients. Efficacy and safety outcomes are risk for recurrent VTE and clinically important bleeding (also as a composite outcome) in patients with thrombophilia. Other outcomes are quality of life and costs. The indication for thrombophilia testing in patients with VTE is intensely debated and depends on the balance between potentially beneficial treatment or preventive strategies on one hand, and potentially harmful effects on the other hand. Thusfar, only opinions of experts who are pro or con thrombophilia testing have been published (4,5), along with few decision analyses that are criticized for the baseline estimates used and that are therefore of limited use (1,6,8). The results of the proposed study will provide direct clinically relevant level 1 evidence on whether testing for thrombophilia is effective in patients with a first episode of VTE. Testing will be effective if patients with thrombophilia benefit from a prolonged course of anticoagulation in terms of a efficacy outcome of recurrent VTE and a safety outcome of clinically important bleeding, as well as the composite of both.. The impact of quality of life of thrombophilia testing in patients with a first episode of VTE will be assessed as well, as well as the costs. To the knowledge of the members of the project group, who represent the majority of academic centers active in thrombophilia research in The Netherlands, no similar studies are underway, either nationally or internationally. A report by national advisory boards on the subject is not available. The CBO Guideline 'Diepe veneuze trombose en longembolie' (1998) does not mention the subject in particular.