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

Vanessa Roldán
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
,
Adriana Ordoñez
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
,
Francisco Marín
2   Servicio de Cardiología, Hospital Virgen de la Arrixaca, Murcia, Spain
,
Esther Zorio
3   Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
,
José M. Soria
4   Unitat d’Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Antonia Miñano
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
,
Francisco España
3   Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
,
Rocio González-Conejero
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
,
Javier Pineda
5   Servicio de Cardiología, Hospital General Universitario, Alicante, Spain
,
Amparo Estellés
3   Centro de Investigación, Hospital Universitario La Fé, Valencia, Spain
,
Jordi Fontcuberta
4   Unitat d’Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
,
Vicente Vicente
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
,
Javier Corral
1   Centro Regional de Hemodonación, Universidad de Murcia, Murcia, Spain
› Author Affiliations
Financial support: Financial support: This project has been partially supported by SAF2006–06212 (Spanish Minister of Science and Education –MEC- and European Found for Development of Regions-FEDER), and RETICS (RECAVA) from the Spanish Institute of Health Carlos III – ISCIII-. A. Ordoñez has a FIS predoctoral fellowship.
Further Information

Publication History

Received: 09 September 2008

Accepted after major revision: 06 January 2008

Publication Date:
24 November 2017 (online)

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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.