High plasma levels of factor VIII and risk of recurrence of venous thromboembolism.

The aim of this study was to evaluate the relationship between factor VIII (FVIII) levels, measured by chromogenic and clotting assays, and risk of venous thromboembolism (VTE) recurrence. A total of 564 patients underwent clinical follow-up after oral anticoagulant withdrawal (total follow-up = 924.4 years). Recurrent VTE developed in 39 of 309 (12.6%) patients with a first idiopathic VTE and in 14 of 255 (5.5%) patients whose first event was secondary. In patients with a first idiopathic VTE, the risk of recurrence was more than fivefold higher in patients with FVIII levels exceeding the 90th percentile [chromogenic FVIII: relative risk (RR) 5.43 (95% CI 1.76-16.8); clotting FVIII: RR 6.21 (95% CI 1.57-24.5)] after adjustment for all possible confounding variables. In patients with a first secondary VTE, the risk of recurrence was slightly higher in patients with high FVIII levels [chromogenic FVIII: RR 2.62 (95% CI 0.34-19.9); clotting FVIII: RR 1.74 (95% CI 0.25-12.1)], but, given the low number of recurrences, the 95% CI were very large. In conclusion, this study shows that high FVIII levels are associated with increased risk of VTE recurrence in patients with a first idiopathic VTE. Although the measurement of FVIII levels by a specific chromogenic assay might, in principle, be preferred to avoid the risk of aspecific clotting effects, no significant differences in results obtained by chromogenic or clotting methods were found.