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

Abstract

SummaryThe 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 ¼ 924AE4 years). Recurrent VTE developed in 39 of 309 (12AE6%) patients with a first idiopathic VTE and in 14 of 255 (5AE5%) 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) 5AE43 (95% CI 1AE76-16AE8); clotting FVIII: RR 6AE21 (95% CI 1AE57-24AE5)] 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 2AE62 (95% CI 0AE34-19AE9); clotting FVIII: RR 1AE74 (95% CI 0AE25-12AE1)], 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.

6 versus 30 months anticoagulation for recurrent venous thrombosis in patients with high factor VIII

“…The probability of recurrence 2 years after discontinuation of anticoagulation was 36% among patients with high factor VIII as compared with 5% among patients with lower levels. These data were confirmed by an Italian study in which recurrence risk of patients with idiopathic VTE was more than fivefold higher, if factor VIII levels exceeded the 90th percentile [4]. In contrast, in the Leiden Thrombophilia Study high factor VIII levels were not associated with an increased risk of recurrence [5].…”

Higher prevalence of thrombophilia in patients with varicose veins and venous ulcers than controls

“…17,26,27 The risk of a first DVT increases by 10% with each 10% increase in activity, even when FVIII values are within the normal range 28,29 ; recurrence of thrombosis is common. 30,31 Hereditary factors appear to set the baseline levels; other factors (obesity, smoking, hormones, exercise, acute phase reactants, eg, infection, inflammation and malignancy) can lead to a further rise. The present study shows CVU and VV patients (to a lesser extent) had significantly increased FVIII levels vs controls.…”

Heparin and warfarin anticoagulation intensity as predictors of recurrence after deep vein thrombosis or pulmonary embolism: a population-based cohort study

“…7 Therefore, we believe that these patients were relatively heparin resistant, possibly because of high factor VIII activity, 35,36 which is a predictor of VTE recurrence. 37 The duration of overlapping heparin and warfarin therapy was not a predictor of VTE recurrence. Given the narrow CIs around our estimated HR of recurrence per day of overlap, it is unlikely that a longer duration of heparin/warfarin overlap provides an important reduction in VTE recurrence risk, and our simulated analyses support this conclusion.…”