D‐dimer, factor VIII coagulant activity, low‐intensity warfarin and the risk of recurrent venous thromboembolism

• Published in: Journal of thrombosis and haemostasis Vol. 4; no. 6; pp. 1208 - 1214
• Main Authors: SHRIVASTAVA, S., RIDKER, P. M., GLYNN, R. J., GOLDHABER, S. Z., MOLL, S., BOUNAMEAUX, H., BAUER, K. A., KESSLER, C. M., CUSHMAN, M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2006
• Subjects: Adult; Aged; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; anticoagulation; Biomarkers - blood; blood coagulation; deep vein thrombosis; Double-Blind Method; Drug Administration Schedule; Factor VIII - metabolism; Female; Fibrin Fibrinogen Degradation Products - metabolism; Humans; Male; Middle Aged; pulmonary embolus; Risk Factors; Secondary Prevention; Thromboembolism - blood; Thromboembolism - drug therapy; Thromboembolism - prevention & control; venous thrombosis; Venous Thrombosis - blood; Venous Thrombosis - drug therapy; Venous Thrombosis - prevention & control; Warfarin - administration & dosage; Warfarin - therapeutic use
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/j.1538-7836.2006.01935.x

Background: Elevated plasma D‐dimer and factor VIII coagulant activity (FVIIIc) may be associated with the risk of recurrent venous thromboembolism (VTE). Objectives: To evaluate D‐dimer and FVIIIc as risk factors for recurrent VTE and assess the efficacy of extended low‐intensity warfarin (target International Normalized Ratio 1.5–2.0) in preventing recurrence by biomarker level. Patients and methods: In the Prevention of Recurrent Venous Thromboembolism trial, 508 idiopathic VTE patients treated for ≥ 3 months with full‐intensity warfarin, and who had stopped warfarin for 7 weeks on average, were randomized to low‐intensity warfarin or placebo and followed for 2.1 years for recurrent VTE. Prerandomization blood samples were analysed for D‐dimer and FVIIIc. Results: One‐third of participants had elevated baseline D‐dimer (≥ 500 ng mL−1) and one‐fourth, elevated FVIIIc (≥ 150 IU dL−1). Adjusting for other risk factors, the hazard ratios (HRs) for recurrent VTE with elevated D‐dimer or FVIIIc were 2.0 [95% confidence interval (CI) 1.2–3.4] and 1.5 (95% CI 0.8–2.8), respectively. The association of elevated D‐dimer with recurrence was larger among patients with one prior VTE (HR 3.2, 95% CI 1.3–8.0) than in patients with more than one event (HR 1.4, 95% CI 0.7–2.2). For patients with one prior VTE on placebo, the annual recurrence incidence was 10.9% with elevated D‐dimer and 2.9% with normal values. Low‐intensity warfarin was equally effective in recurrence risk reduction in those with normal or elevated biomarkers. Conclusions: Among patients with idiopathic VTE, measurement of D‐dimer, but not FVIIIc, might be useful for risk stratification. The efficacy of extended low‐intensity warfarin therapy did not vary by biomarker level.