Predictive value of factor VIII levels for recurrent venous thrombosis: results from the MEGA follow-up study.

Background: Prediction of recurrent venous thrombosis remains a challenge in the clinic.

Objective: To investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis.

Patients/methods: Patients, aged 18-70 years with a first venous thrombosis, were followed from discontinuation of anticoagulant treatment (1999-2010 MEGA follow-up study). The levels of FVIII activity, FVIII antigen and von Willebrand factor (VWF) antigen were measured at least 3 months after cessation of anticoagulant treatment.

Results: Of 2242 patients followed for a median of 6.9 years, 343 developed recurrent thrombosis (incidence rate 2.7/100 patient-years; 95% confidence interval [CI] 2.5-3.1). Recurrence rates steadily increased with higher FVIII activity levels, from 1.4 (95% CI 1.0-1.9), 2.3 (95% CI 1.8-2.9), 3.0 (95% CI 2.4-3.7), 3.2 (95% CI 2.5-4.1), 3.9 (95% CI 2.8-5.3) to 5.1 (95% CI 3.8-6.8) per 100 patient-years, for levels ranging from < 100 IU dL(-1) to > 200 IU dL(-1) . Patients in the highest category of FVIII (> 200 IU dL(-1) ) had a three-fold higher recurrence rate than patients in the lowest category (≤ 100 IU dL(-1) ) (hazard ratio 3.4; 95% CI 2.2-5.3). Results were similar for FVIII antigen and VWF antigen levels, in several sensitivity analyses, and FVIII predicted recurrence rates over a long time period. Within subgroups of patients currently assumed to have low recurrence risks, a high level of FVIII was still predictive for recurrences. Adding FVIII to an existing prediction model (DASH score) improved its predictive value, and, after replacement of D-dimer with FVIII, the model performed equally well, if not better.

Conclusions: FVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools.