A Reduced Sensitivity for Activated Protein C in the Absence of Factor V Leiden Increases the Risk of Venous Thrombosis
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- Marieke C.H. de Visser
- From the Hemostasis and Thrombosis Research Center, Department of Hematology, and the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
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- Frits R. Rosendaal
- From the Hemostasis and Thrombosis Research Center, Department of Hematology, and the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
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- Rogier M. Bertina
- From the Hemostasis and Thrombosis Research Center, Department of Hematology, and the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Abstract
<jats:title>Abstract</jats:title> <jats:p>Activated protein C (APC) resistance caused by the factor V Leiden mutation is associated with an increased risk of venous thrombosis. We investigated whether a reduced response to APC, not due to the factor V point mutation, is also a risk factor for venous thrombosis. For this analysis, we used the Leiden Thrombophilia Study (LETS), a case-control study for venous thrombosis including 474 patients with a first deep-vein thrombosis and 474 age- and sex-matched controls. All carriers of the factor V Leiden mutation were excluded. A dose-response relationship was observed between the sensitivity for APC and the risk of thrombosis: the lower the normalized APC sensitivity ratio, the higher the associated risk. The risk for the lowest quartile of normalized APC-SR (<0.92), which included 16.5% of the healthy controls, compared with the highest quartile (normalized APC-SR > 1.05) was greater than fourfold increased (OR = 4.4; 95% confidence interval, 2.9 to 6.6). We adjusted for VIII:C levels, which appeared to affect our APC resistance test. The adjusted (age, sex, FVIII:C) odds ratio for the lowest quartile was 2.5 (95% confidence interval, 1.5 to 4.2). So, after adjustment for factor VIII levels, a reduced response to APC remained a risk factor. Our results show that a reduced sensitivity for APC, not caused by the factor V Leiden mutation, is a risk factor for venous thrombosis.</jats:p>
Journal
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- Blood
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Blood 93 (4), 1271-1276, 1999-02-15
American Society of Hematology
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Keywords
Details 詳細情報について
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- CRID
- 1362544420766293632
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- ISSN
- 15280020
- 00064971
- http://id.crossref.org/issn/00064971
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- Data Source
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- Crossref