Antithrombin Cambridge II (A384S) supports a role for antithrombin deficiency in arterial thrombosis
- 1 January 2009
- journal article
- Published by Georg Thieme Verlag KG in Thrombosis and Haemostasis
- Vol. 101 (03), 483-486
- https://doi.org/10.1160/th08-09-0583
Abstract
Although the control of thrombin in the microvasculature at the endothelial cell surface is crucial to prevent atherothrombosis, the role of antithrombin in arterial thrombosis is unclear. It is widely considered that antithrombin deficiency is unlikely to contribute to arterial thrombosis, but no convincing epidemiological study has been performed because of the low frequency of this deficiency. In this study we evaluated the role in myocardial infarction (MI) of a relatively common mutation affecting antithrombin gene (A384S: Antithrombin Cambridge II) that has functional features that may impair the right control of thrombogenic events caused by injury to the vascular wall. Moreover, this deficiency, which is not detected using common methods to diagnose antithrombin deficiency, also increases the risk of venous thrombosis. We included 1,224 patients with MI (691 consecutive patients and 533 survivors of a premature event), and 1,649 controls. The mutation was identified in 0.3% of controls, but 0.8% of MI patients. After adjusting for sex and other cardiovascular risk factors, the antithrombin Cambridge II significantly increased 5.66-fold the risk of MI (95% CI: 1.53–20.88; p= 0.009). Interestingly, young patients had the highest risk of MI associated with the mutation (OR: 9.98; 95%CI: 1.60–62.24; p= 0.009). This is the first epidemiological study that supports a role for anti-thrombin deficiency in arterial thrombosis. These results suggest that deficiency of antithrombin may be an independent risk factor for MI that has been underestimated, but larger studies are needed to confirm the relevance of inhibitors of thrombin in arterial thrombosis.Funding Information
- Spanish Minister of Science and Education –MEC- and European Found for Development of Regions-FEDER (SAF2006–06212)
This publication has 21 references indexed in Scilit:
- Inherited Thrombophilia in Arterial Disease: A Selective ReviewSeminars in Hematology, 2007
- Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosisBlood, 2007
- Seven haemostatic gene polymorphisms in coronary disease: meta-analysis of 66 155 cases and 91 307 controlsThe Lancet, 2006
- Gene polymorphisms of the haemostatic system and the risk of arterial thrombotic diseaseBritish Journal of Haematology, 2001
- Complete antithrombin deficiency in mice results in embryonic lethalityJCI Insight, 2000
- Thrombin signalling and protease-activated receptorsNature, 2000
- Rapid Genetic Diagnosis in Neonatal Pulmonary Artery Thrombosis Caused by Homozygous Antithrombin Budapest 3Clinical and Applied Thrombosis/hemostasis, 2000
- Prevalence of antithrombin deficiency in the healthy populationBritish Journal of Haematology, 1994
- Deficiency of plasma protein S, protein C, or antithrombin III and arterial thrombosis.Arteriosclerosis: An Official Journal of the American Heart Association, Inc., 1987
- Inhibitors of Coagulation, Atherosclerosis, and Arterial ThrombosisSeminars in Thrombosis and Hemostasis, 1986