A test that measures the generation of a certain protein involved with blood clotting can help determine whether patients who have experienced a venous blood clot are at low risk of developing another blood clot, and thus avoiding anticoagulant treatment and its possible side effects, according to a study in the July 26 issue of JAMA.
Anticoagulant treatment for patients with venous thromboembolism (VTE - formation of blood clots, often involving the deep veins of the legs or in the lung) consists of heparin followed by vitamin K antagonists for at least 3 to 6 months. After discontinuation of anticoagulant treatment, a third of patients experience recurrence of VTE within the next 5 to 8 years, according to background information in the article. The case-fatality rate of recurrence is around 5 percent. Therefore, identification of patients who might benefit from indefinite anticoagulant treatment (i.e., patients in whom recurrent VTE is more likely than anticoagulation-associated severe bleeding) is now one of the foremost goals in thrombosis research. Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A laboratory test that would detect multifactorial thrombophilia (increased tendency for blood clots) could help determine the overall risk of recurrent VTE.
Gregor Hron, M.D., of the Medical University of Vienna, Austria and colleagues conducted a study to determine whether by measuring thrombin generation (a protein in blood that causes clotting), patients with VTE could be stratified into high- and low-risk categories for recurrence of VTE. The study, conducted between July 1992 and July 2005, included 914 patients with first spontaneous VTE who were followed-up for an average of 47 months after discontinuation of vitamin K antagonist therapy. Thrombin generation was measured by a commercially available test.
Venous thromboembolism recurred in 100 patients (11 percent). The researchers found that patients without recurrent VTE had lower thrombin generation than patients with recurrence.
"In this large prospective cohort study, we found that patients with a first spontaneous VTE and peak thrombin generation of less than 400 nM [the measurement nanomolar] after discontinuation of vitamin K antagonists have a low risk of recurrence. According to Kaplan-Meier analysis, the likelihood of recurrent VTE in these patients was as low as 7 percent after 4 years. … Compared with patients who had higher levels, those with peak thrombin generation less than 400 nM had an almost 60 percent lower risk of recurrence. Most importantly, the group of patients with low peak thrombin generation represented two-thirds of the total patient population," the authors write.
"… we believe that our findings are of major clinical relevance. Using a simple commercially available laboratory method developed to measure thrombin generation, we were able to identify patients in whom the long-term risk of recurrent VTE is almost negligible. Considering the incidence rates of severe or fatal hemorrhage related to anticoagulant therapy and the case-fatality rate of recurrent VTE, patients with low peak thrombin generation (less than 400 nM) would almost certainly not benefit from indefinite anticoagulant therapy. Consequently, extensive thrombophilia screening appears to be unnecessary in this large, low-risk patient group," the researchers conclude. (JAMA. 2006;296:397-402. Available pre-embargo to the media at www.jamamedia.org)
Editor's Note: Co-author Dr. Binder has reported that he is chief scientific officer for Technoclone GmbH, Vienna, Austria. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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