title: Recombinant activated factor VII and tranexamic acid are haemostatically effective during major surgery in factor XI-deficient patients with inhibitor antibodies.
abstract: 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 microg/ml) induced thrombin generation in FXI-deficient plasma quite similarly to 1.9 microg/ml (a concentration that is achieved in patients with haemophilia A and inhibitor after infusion of 80 microg/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.
authors.affiliation: The Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Tami
authors.initials: T
authors.lastname: Livnat
authors.forename: Ilia
authors.initials: I
authors.lastname: Tamarin
authors.forename: Yoram
authors.initials: Y
authors.lastname: Mor
authors.forename: Harry
authors.initials: H
authors.lastname: Winckler
authors.forename: Zeev
authors.initials: Z
authors.lastname: Horowitz
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Korianski
authors.forename: Barak
authors.initials: B
authors.lastname: Bar-Zakay
authors.forename: Uri
authors.initials: U
authors.lastname: Seligsohn
authors.forename: Ophira
authors.initials: O
authors.lastname: Salomon
mesh_terms: D000483:Alleles; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D015942:Factor VIIa / Q000378:metabolism*; D005172:Factor XI / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005173:Factor XI Deficiency / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006467:Hemophilia A / Q000235:genetics; D006487:Hemostasis; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000737:chemistry; D013927:Thrombosis; D013997:Time Factors; D014148:Tranexamic Acid / Q000378:metabolism*
chemical_list: D014148:Tranexamic Acid; D005172:Factor XI; D015942:Factor VIIa; D013917:Thrombin