Letter by Kovacs Regarding Article, “Diagnosis and Management of Cerebral Venous Thrombosis: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association”
To the Editor:
The American Heart Association scientific statement with respect to diagnosis and management of cerebral vein thrombosis contains recommendations about thrombophilia testing that are common misconceptions.1 First, it states that proteins C and S, as well as antithrombin levels, are difficult to interpret during treatment with warfarin. It is not correct that antithrombin levels cannot be interpreted while patients are on warfarin. Antithrombin levels are affected by unfractionated heparin or by a recent large dose of low-molecular-weight heparin, but not by warfarin.
It is also a common misconception that proteins C and S cannot be interpreted at the time of an acute thrombotic event. There are no studies to support this statement. We have published 2 studies that support assessment of protein C and protein S at the time of an acute thrombotic event prior to initiation of warfarin.2,3 We found that 484 of 508 tests (95.3%) for protein C or protein S were normal when drawn before initiation of warfarin.2 When abnormal tests were repeated after 3 to 6 months (when the patients were taken off of warfarin), 48% were still abnormal (ie, were true positive). Thus, overall, 98.8% of initial protein C and protein S results were accurate. Since all clotting-based assays, such as protein C and protein S, that are abnormal ought to be confirmed on repeat testing off of warfarin therapy at least once, the very small percent of false-positive results are not of any concern; they will be identified.
It has also been suggested that normal protein C and protein S results at the time of acute venous thromboembolism could be falsely normal. In response, we took 99 patients who had normal protein C and protein S at the time of acute thrombotic event, and repeated testing when the patients were off of warfarin. None had abnormal results on repeat testing.2
Therefore, it is valid to assess protein C and protein S at the time of acute venous thromboembolism prior to initiation of warfarin, with the caveat that the very small number of positive results should be repeated at a later date off of warfarin, to make sure the result is not a false positive.
Michael J. Kovacs, MD, FRCPC
Department of Hematology
London Health Sciences Centre
London, Ontario, Canada
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- © 2011 American Heart Association, Inc.