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Prepublished online as a Blood First Edition Paper on September 26, 2002; DOI 10.1182/blood-2002-05-1416.
Submitted May 15, 2002
Accepted September 17, 2002
Fibrin fragment D-dimer and the risk of future venous thrombosis
Mary Cushman*, Aaron R Folsom, Lu Wang, Nena Aleksic, Wayne D Rosamond, Russell P Tracy, and Susan R Heckbert
Department of Medicine, University of Vermont, Colchester, VT, USA; Department of Pathology, University of Vermont, Colchester, VT, USA
Division of Epidemiology, University of Minnesota School of Public Health, Minneapolis, MN, USA
Department of Internal Medicine, University of Texas, Houston, Houston, TX, USA
Department of Epidemiology, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA
Department of Pathology, University of Vermont, Colchester, VT, USA; Department of Biochemistry, University of Vermont, Colchester, VT, USA
Department of Epidemiology, University of Washington, Seattle, WA, USA
* Corresponding author; email: mary.cushman{at}uvm.edu.
Plasma D-dimer concentration rises more than one-hundred fold during acute deep vein thrombosis, but there are no prospective data concerning D-dimer as a risk factor for incident venous thrombosis in a general population. Incident venous thrombosis was ascertained in two prospective observational studies, the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Of 21,690 participants enrolled between 1987 and 1993, after 8 years of follow-up, D-dimer was measured using baseline stored plasma of 307 participants who developed venous thrombosis and 616 who did not. Relative to the first quintile of the distribution of D-dimer, the age-adjusted odds ratios for future venous thrombosis for the second to fifth quintiles of D-dimer were 1.6, 2.3, 2.3, and 4.2, respectively (p for trend < 0.0001). Following added adjustment for sex, race, body-mass index, factor V Leiden, prothrombin 20210A, and elevated factor VIIIc these odds ratios were 1.5, 2.1, 1.9, and 3.0, respectively (p for trend < 0.0001). Among those with idiopathic thrombosis or secondary thrombosis unrelated to cancer, the adjusted fifth quintile odds ratios were 3.5 and 4.8, respectively. By contrast, D-dimer in the fifth versus first quintile was not related to occurrence of cancer-associated thrombosis (odds ratio 1.1). Odds ratios for elevated D-dimer were consistently elevated in subgroups defined by age, sex, race, duration of follow up, and thrombosis type (deep vein thrombosis or pulmonary embolus). D-dimer is strongly and positively related to the occurrence of future venous thrombosis.
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