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

BackgroundPrediction of recurrent venous thrombosis remains a challenge in the clinic. ObjectiveTo investigate the predictive value of coagulation factor VIII (FVIII) levels for recurrent venous thrombosis. Patients/methodsPatients, aged 18-70years 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 3months after cessation of anticoagulant treatment. ResultsOf 2242 patients followed for a median of 6.9years, 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%CI1.0-1.9), 2.3 (95%CI1.8-2.9), 3.0 (95%CI2.4-3.7), 3.2 (95%CI 2.5-4.1), 3.9 (95%CI2.8-5.3) to 5.1 (95%CI3.8-6.8) per 100 patient-years, for levels ranging from <100IUdL(-1) to >200IUdL(-1). Patients in the highest category of FVIII (>200IUdL(-1)) had a three-fold higher recurrence rate than patients in the lowest category (100IUdL(-1)) (hazard ratio 3.4; 95%CI2.2-5.3). 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. ConclusionsFVIII predicted recurrence in a dose-response fashion, overall and in several subgroups, and is a strong candidate component of recurrence prediction tools.