High plasma levels of factor VIII and the risk of recurrent venous thromboembolism

N Engl J Med. 2000 Aug 17;343(7):457-62. doi: 10.1056/NEJM200008173430702.


Background: A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients with high plasma levels of factor VIII.

Methods: We studied 360 patients for an average follow-up period of 30 months after a first episode of venous thromboembolism and discontinuation of oral anticoagulants. Patients who had recurrent or secondary venous thromboembolism, a congenital deficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism.

Results: Recurrent venous thromboembolism developed in 38 of the 360 patients (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosis was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values in the study population, the likelihood of recurrence at two years was 37 percent, as compared with a 5 percent likelihood among patients with lower levels (P<0.001). Among patients with plasma factor VIII levels above the 90th percentile, as compared with those with lower levels, the overall relative risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden or the G20210A prothrombin mutation, and the duration of oral anticoagulation.

Conclusions: Patients with a high plasma level of factor VIII have an increased risk of recurrent venous thromboembolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Factor VIII / analysis*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Embolism / blood*
  • Recurrence
  • Risk
  • Risk Factors
  • Venous Thrombosis / blood*


  • Factor VIII