Elevated factor VIII is a risk factor for idiopathic venous thromboembolism in Canada – is it necessary to define a new upper reference range for factor VIII?

Philip S. Wells; Nicole J. Langlois; Marc A. Webster; James Jaffey; Josdalyne A. Anderson

doi:10.1160/TH05-01-0013

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2005; 93(05): 842-846
DOI: 10.1160/TH05-01-0013

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Elevated factor VIII is a risk factor for idiopathic venous thromboembolism in Canada – is it necessary to define a new upper reference range for factor VIII?

Authors

Philip S. Wells

¹Departments of Medicine, University of Ottawa, Ottawa, Canada

⁴Department of Medicine, Ottawa Hospital, Ottawa, Canada
Nicole J. Langlois

³Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
Marc A. Webster

¹Departments of Medicine, University of Ottawa, Ottawa, Canada
James Jaffey

³Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada

⁴Department of Medicine, Ottawa Hospital, Ottawa, Canada
Josdalyne A. Anderson

³Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada

Abstract

Summary

Previous studies suggest elevated factor VIII is a common, independent risk factor for venous thromboembolism (VTE); however, these studies included secondary and idiopathic VTE. We sought to explore the association between elevated factor VIII and VTE in Canadian patients with idiopathic thrombosis, and confirm the current upper factor VIII reference range was appropriate. We enrolled 300 consecutive patients with idiopathic VTE who were matched to friend controls by age, sex and ethnicity. Factor VIII levels were measured and compared between cases and controls. The optimal cut-off value to designate factor VIII levels as elevated was determined using a variety of methods. The optimal upper cut-off value for factor VIII levels was 270 IU/dl. In the logistic regression analysis, cases were more likely to have elevated factor VIII levels (OR:8.76), as were females (OR:1.93) and older subjects (OR:1.05). Factor VIII cutoffs for a 95% specificity by age were 238 IU/dl for subjects <40 years, 248 IU/dl age 40–55 years, 261 IU/dl age 56–70 years, and 313 IU/dl age >70. Our findings confirm that elevated factor VIII is associated with an increased risk of idiopathic VTE. In our patients and matched controls, the current upper limit of normal (150 IU/dl) for factor VIII is not of clinical use. We propose that the upper limit be increased to 270 IU/dl or individual labs should establish their upper limit if they wish their assays to be discriminatory in patients with VTE. Age specific cut-offs may be clinically relevant.

Keywords

Case-control - factor VIII - risk factors - thrombophilia - venous thromboembolism

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Referenzen

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