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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:731.)
© 2001 American Heart Association, Inc.

Brief Review

Elevated Factor VIII Levels and the Risk of Thrombosis

Pieter W. Kamphuisen; Jeroen C. J. Eikenboom; Rogier M. Bertina

From the Hemostasis and Thrombosis Research Center, Department of Hematology, Leiden University Medical Center, Leiden, the Netherlands.

Correspondence to Rogier M. Bertina, Hemostasis and Thrombosis Research Center, Leiden University Medical Center, C2-R, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail R.M.Bertina@lumc.nl

Key Words: thrombosis • factor VIII • von Willebrand factor • blood group

	Introduction

 
In vivo, a delicate balance exists between fibrin formation and fibrinolysis. Reduced blood flow, changes in the vessel wall, and changes in blood composition (hypercoagulability)¹ may all result in a disturbance of this balance, which favors fibrin formation and ultimately may lead to the formation of occlusive thrombi. Venous thromboembolism is the result of clot formation in a vein at sites of reduced blood flow. Arterial thrombosis involves the formation of platelet aggregates at high shear rates at sites of vessel-wall injury.

Classic acquired risk factors for venous thrombosis include trauma, immobilization, pregnancy, surgery, malignancy, and infection. These are all factors that may cause tissue damage, stasis of the blood, or changes in blood composition. Inherited risk factors for venous thrombosis,^{2 3 4 5} most of which concern defects in the procoagulant and anticoagulant pathways, account for a substantial proportion of all thrombotic events. Table 1 summarizes prevalences and relative risks of established genetic risk factors.^{6 7 8 9}

View this table: [in this window] [in a new window]   Table 1. Genetic Risk Factors for Venous Thrombosis: Prevalence and Relative Risk

These risk factors include factor V Leiden (resistance to activated protein C [APC]),⁹ prothrombin 20210A,⁸ and deficiencies in antithrombin,² protein C,^{3 4} and protein S.^{5 10 11} Elevated fibrinogen,¹² antiphospholipid antibodies,¹³ and mild hyperhomocysteinemia¹⁴ are examples of laboratory phenotypes associated with venous thrombosis. Some of these phenotypes have also been found to be associated with arterial thrombosis.^{15 16 17} Whether this is also true for genetic risk factors such as factor V Leiden or the prothrombin 20210A allele is still uncertain.^{18 19 20 21 22 23 24 25 26}

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