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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4258-4263. Prepublished online as a Blood First Edition Paper on January 23, 2007; DOI 10.1182/blood-2006-08-040774. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-040774v1 109/10/4258    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Corral, J. Articles by Vicente, V. Search for Related Content PubMed PubMed Citation Articles by Corral, J. Articles by Vicente, V. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 11, 2006 Accepted January 5, 2007 Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis Javier Corral*, David Hernandez-Espinosa, Jose Manual Soria, Rocio Gonzalez-Conejero, Adriana Ordonez, Jose Ramon Gonzalez-Porras, Elena Perez-Ceballos, Ramon Lecumberri, Ignacio Sanchez, Vanessa Roldan, Jose Mateo, Antonia Minano, Marcos Gonzalez, Ignacio Alberca, Jordi Fontcuberta, and Vicente Vicente Centro Regional de Hemodonacion, Universidad de Murcia, Spain Unitat d'Hemostasia i Trombosi, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain Hematology Service, Hospital Clinico Universitario, Salamanca, Spain Hematology Service, Clinica Universitaria de Navarra, Pamplona, Spain * Corresponding author; email: javier.corral{at}carm.es. The antithrombin A384S mutation has a relatively high frequency in the British population but has not been identified in other populations. This variant has been associated with cases of thrombotic disease, but its clinical relevance in venous thrombosis remained unclear. We have conducted a secondary analysis of the prevalence of the mutation in a large case-control study including 1018 consecutive Spanish patients with venous thromboembolism. In addition, we evaluated its functional consequences in 20 carriers (4 homozygous). This mutation, even in the homozygous state, did not affect anti-Xa activity nor antigen levels, and only slightly impaired anti-IIa activity. Thus, routine clinical methods cannot detect this anomaly, and accordingly, this alteration could have been underestimated. We identified this mutation in 0.2% of Spanish controls. Among patients, this variant represented the first cause of antithrombin anomalies. Indeed, 1.7% patients carried the A384S mutation but 0.6% had any other antithrombin deficiency. The mutated allele was associated with an increased risk of venous thrombosis with an adjusted OR of 9.75 (95% CI: 2.2-42.5). This is the first study supporting that antithrombin A384S mutation is a prevalent genetic risk factor for venous thrombosis and is the most frequent cause of antithrombin deficiency in Caucasian populations. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: V. Picard, I. Presot, P.-Y. Scarabin, M. Aiach, J. Emmerich, and M. Alhenc-Gelas Antithrombin Cambridge II (A384S): prevalence in patients of the Paris Thrombosis Study (PATHROS) Blood, October 1, 2007; 110(7): 2777 - 2778. [Full Text] [PDF]

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