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Thromb Haemost 2009; 102(03): 487-492
DOI: 10.1160/TH09-03-0172
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies

Tami Livnat
1   The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Ilia Tamarin
1   The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Yoram Mor
2   Department of Urology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Harry Winckler
2   Department of Urology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Zeev Horowitz
3   Department of Otolaryngology, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Yoseph Korianski
4   Department of Surgery, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Barak Bar-Zakay
4   Department of Surgery, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Uri Seligsohn
1   The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
,
Ophira Salomon
1   The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Israel
› Author Affiliations
Further Information

Publication History

Received: 18 March 2009

Accepted after major revision: 20 May 2009

Publication Date:
22 November 2017 (online)

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Summary

One-third of patients with severe factor XI (FXI) deficiency caused by homozygosity for null alleles develop inhibitor antibodies following exposure to plasma. Haemostasis during surgery is achievable in such patients by recombinant activated factor VII (rFVIIa) at doses used in haemophilia A patients with an inhibitor to FVIII. However, thrombosis has occurred in three of 12 such patients. In this study we discerned whether low-dose rFVIIa would secure haemostasis and cause no thrombosis in patients with severe FXI deficiency and an inhibitor during surgery. In vitro, a very low concentration of rFVIIa (0.24 µg/ml) induced thrombin generation in FXI-deficient plasma quite similarly to 1.9 µg/ml (a concentration that is achieved in patients with haemophilia A and inhibitor after infusion of 80 µg/kg). Based on this finding, a protocol was designed for four patients with severe FXI deficiency and an inhibitor or immunoglobulin A deficiency who underwent five major surgical procedures. This included administration of tranexamic acid from two hours before surgery until seven to 14 days after, and single infusion of low-dose rFVIIa. No excessive bleeding or thrombosis were observed. In conclusion, a single low dose of rFVIIa and tranexamic acid secure normal haemostasis in patients with severe FXI deficiency who can not receive blood products.

Keywords

Factor XI - factor XI inhibitor - immunoglobulin A deficiency - recombinant factor VIIa - thrombin generation
 

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