Controversies in hypercoagulability
Recent guidelines have recommended testing certain patients for hypercoagulable states following an episode of venous thromboembolism (VTE) and others suggest how such test results might influence treatment decisions. But controversy arose last May with the publication of this study in JAMA of patients who underwent thrombophilia testing after an episode of VTE. The study showed that certain clinical factors, but not laboratory testing, were predictive of recurrent VTE events. The popular spin, simplistic as always, was that thrombophilia testing be abandoned.
How can this seemingly disparate evidence be integrated with what was known before? Older data, upon which the guidelines were based, had established that thrombophilia testing was predictive of the relative risk for initial VTE. The situation is completely different for patients who have already had a spontaneous VTE. Why? It has long been known that patients with spontaneous VTE are hypercoagulable, (untreated recurrence rates of 2% to 5% per year) no matter the result of thrombophilia testing. In part this is because comprehensive laboratory testing of clinically thrombophilic patients will yield negative results---no “laboratory lesion”--- in about 30%-40% of cases. The thinking is that those patients have a thrombophilic state that hasn’t been discovered yet. To keep it in perspective, remember that the concept of hereditary thrombophilia has been around since the discovery, in 1963, of antithrombin deficiency (Egeberg O: Inherited antithrombin deficiency causing thrombophilia. Thrombosis Diathesis Haemorrhagica 1963; 13: 516) but it was not until about a decade ago that the most common hereditary thrombophilia, Factor V Leiden, was discovered. The field will mature and as additional disorders are characterized thrombophilia testing will become more “evidence based.”
In a related controversy “NORVIT: Randomised trial of homocysteine-lowering with B vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction” was presented at the European Society of Cardiology this year. The media spin---that the homocysteine hypothesis is a “bust”---was irresponsible. Forget the media reports and view the presentation slides. What the study actually did was to suggest that the popular notion of an upper “safe” limit of homocysteine for cardiovascular health of 9 or 10 may not be valid. It also debunked the popular practice (which was never evidence based in the first place) of giving everyone combination B vitamins for secondary prevention. Homocysteine testing and selective use of folic acid and/or B6 may be clinically valid.