Antithrombin Cambridge II (A384S) supports a role for antithrombin deficiency in arterial thrombosis

Vanessa Roldán; Adriana Ordoñez; Francisco Marín; Esther Zorio; José M. Soria; Antonia Miñano; Francisco España; Rocio González-Conejero; Javier Pineda; Amparo Estellés; Jordi Fontcuberta; Vicente Vicente; Javier Corral

doi:10.1160/TH08-09-0583

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2009; 101(03): 483-486
DOI: 10.1160/TH08-09-0583

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Antithrombin Cambridge II (A384S) supports a role for antithrombin deficiency in arterial thrombosis

Authors

Vanessa Roldán

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
Adriana Ordoñez

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
Francisco Marín

²Servicio de Cardiología, Hospital Virgen de la Arrixaca, Murcia, Spain
Esther Zorio

³Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
José M. Soria

⁴Unitat d’Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Antonia Miñano

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
Francisco España

³Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
Rocio González-Conejero

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
Javier Pineda

⁵Servicio de Cardiología, Hospital General Universitario, Alicante, Spain
Amparo Estellés

³Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
Jordi Fontcuberta

⁴Unitat d’Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Vicente Vicente

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
Javier Corral

¹Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain

Abstract

Summary

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.

Keywords

Genetics - myocardial infarction - thrombosis - risk factors - anticoagulants

Full Text

References

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