Thromb Haemost 2017; 117(06): 1040-1051
DOI: 10.1160/TH16-08-0635
Coagulation and Fibrinolysis
Schattauer GmbH

Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency

Martine Alhenc-Gelas
1  Hématologie biologique, AP-HP Hôpital Européen G Pompidou, Hôpitaux Universitaires Paris Ouest, Paris, France
Genevieve Plu-Bureau
2  Unité d’hémostase, AP-HP, Hôpital Cochin, Hôpitaux universitaires Paris Centre, Faculté de Médecine Paris Descartes, Paris, France
Justine Hugon-Rodin
3  Unité de Gynécologie endocrinienne, AP-HP, Hôpital Cochin, Hôpitaux universitaires Paris Centre, Faculté de Médecine Paris Descartes, Paris, France
Veronique Picard
4  Laboratoire d’Hématologie, AP-HP Hôpital Bicêtre, Hôpitaux Universitaires Paris Sud, Le Kremlin Bicêtre, France
Marie-Helene Horellou
5  Laboratoire d’Hématologie, AP-HP Hôpital Cochin, Hôpitaux universitaires Paris Centre Faculté de Médecine Paris Descartes, Paris, France
GFHT study group on Genetic Thrombophilia› Author Affiliations
Financial support: This study was supported in part by a DHOS program „Soutien financier en faveur des laboratoires pratiquant le diagnostic par génétique moléculaire des maladies rares”.
Further Information

Publication History

Received: 17 August 2016

Accepted after major revision: 23 February 2017

Publication Date:
07 November 2017 (online)


Inherited quantitative (type I) or qualitative (type II) antithrombin deficiency (ATD) due to mutations in the SERPINC1 gene is a well-known risk factor for venous thromboembolism. ATD may also increase risk for arterial thrombosis. Few studies have investigated risk for thrombosis according to mutations. We addressed this topic in a large retrospective cohort study of 540 heterozygous carriers of SERPINC1 mutations and compared risk for first venous or arterial thrombosis associated with carrying of different type II or type I mutations. No clear difference in risk for first venous thrombotic event was observed among type I (missense or null), type IIRS or type IIPE mutation carriers except for a few variants that displayed lower risk [all events, adjusted relative risk: Cambridge II: 0.42 (95%CI 0.25–0.70), Dublin: 0.35 (95%CI 0.13–0.99)]. IIHBS mutation carrying was associated with a clearly lower risk than type I mutation carrying [0.28 (95%CI 0.20–0.40)]. These differences in risk were observed for both all venous thrombotic events and pulmonary embolism associated with deep venous thrombosis. The HBS group was also heterogeneous, with AT Budapest 3 carriers displaying a non-significantly different risk [0.61 (95%CI 0.31–1.20)] compared to type I mutation carriers. We also studied risk for arterial thrombosis and found no significant influence of mutation type. Altogether, our findings suggest a place for SERPINC1 genotyping in the diagnosis of ATD.

Supplementary Material to this article is available online at