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Eichinger S, Minar E, Bialonczyk C, et al. D-Dimer Levels and Risk of Recurrent Venous Thromboembolism. JAMA. 2003;290(8):1071–1074. doi:10.1001/jama.290.8.1071
Author Affiliations: Department of Internal Medicine I (Drs Eichinger, Weltermann, and Kyrle), Ludwig-Boltzmann Institute (Dr Kyrle), Department of Internal Medicine II (Dr Minar), Clinical Institute of Medical and Chemical Laboratory Diagnostics (Drs Quehenberger and Wagner), and Institute of Medical Statistics (Dr Schneider), University of Vienna, Austria; and Wilhelminenspital (Dr Bialonczyk) and Hanuschkrankenhaus (Dr Hirschl), Vienna, Austria.
Context Widespread screening of patients with venous thromboembolism (VTE) for
thrombophilic risk factors has become common clinical practice. Because of
the increasing number of risk factors, assessing the risk of recurrence in
an individual patient is intricate; therefore, a laboratory method that measures
multifactorial thrombophilia is required.
Objective To prospectively study the relationship between the risk of recurrent
VTE and D-dimer, a global marker of coagulation activation and fibrinolysis.
Design, Setting, and Participants Prospective cohort study of 610 patients older than 18 years who were
treated with oral anticoagulants for at least 3 months with a first spontaneous
VTE, in whom D-dimer levels were measured shortly after discontinuation of
oral anticoagulation. The study was conducted at the Department of Internal
Medicine I, University Hospital, Vienna, Austria. Patients entered the study
at time of discontinuation of oral anticoagulants and were observed at 3-month
intervals during the first year and every 6 months thereafter from July 1992
to October 2002.
Main Outcome Measure Objectively documented symptomatic recurrent VTE.
Results A total of 79 (13%) of 610 patients had recurrent VTE with a mean observation
time of 38 months. Patients with recurrence had significantly higher D-dimer
levels compared with those without recurrence (553 ng/mL vs 427 ng/mL, P = .01). Compared with patients with D-dimer levels of
750 ng/mL or higher, the relative risk (RR) of recurrence was 0.6 (95% confidence
interval [CI], 0.3-1.4), 0.6 (95% CI, 0.3-1.2), and 0.3 (95% CI, 0.1-0.6)
in patients with D-dimer levels of 500 to 749 ng/mL, 250 to 499 ng/mL, and
less than 250 ng/mL, respectively. The cumulative probability of recurrent
VTE at 2 years was 3.7% (95% CI, 0.9%-6.5%) among patients with D-dimer levels
of less than 250 ng/mL compared with 11.5% (95% CI, 8.0%-15.0%) among patients
with higher levels (P = .001). Patients with D-dimer
levels of less than 250 ng/mL had a 60% lower RR of recurrence compared with
patients with higher levels (RR, 0.4; 95% CI, 0.2-0.8).
Conclusion Patients with a first spontaneous VTE and a D-dimer level of less than
250 ng/mL after withdrawal of oral anticoagulation have a low risk of VTE
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