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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?

Philip S. Wells
1   Departments of Medicine, University of Ottawa, Ottawa, Canada
4   Department of Medicine, Ottawa Hospital, Ottawa, Canada
,
Nicole J. Langlois
3   Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
,
Marc A. Webster
1   Departments of Medicine, University of Ottawa, Ottawa, Canada
,
James Jaffey
3   Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
4   Department of Medicine, Ottawa Hospital, Ottawa, Canada
,
Josdalyne A. Anderson
3   Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Canada
› Author AffiliationsFinancial support: This study was supported, in part, by the Heart and Stroke Foundation of Ontario, Grant NA4507. Dr. Wells is a Canada Research Chair.
Further Information

Publication History

Received 07 January 2005

Accepted after revision 24 February 2005

Publication Date:
11 December 2017 (online)

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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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