title: Antithrombin alfa in hereditary antithrombin deficient patients: A phase 3 study of prophylactic intravenous administration in high risk situations.
abstract: During surgery and childbirth, patients with hereditary antithrombin (AT) deficiency are at high risk for thrombosis, and heparin prophylaxis may not be sufficiently efficacious. In these patients, exogenous AT may be used in association with heparin. A recombinant human AT (generic name: antithrombin alfa) has been developed. This multi-center study assessed the efficacy and safety of prophylactic intravenous administration of antithrombin alfa to hereditary AT deficient patients in high risk situations, including elective surgery, childbirth, or cesarean section. Antithrombin alfa was administered prior to and during the high risk period for restoration and maintenance of AT activity at 100% of normal. Heparin, low-molecular-weight heparin, and/or vitamin K antagonists were used according to standard of care. The primary efficacy endpoint was the incidence of acute deep vein thrombosis (DVT) from baseline up to day 30 post dosing as assessed by independent central review of duplex ultrasonograms and/or venograms. Safety was assessed based on adverse events (AEs) and laboratory evaluations. Five surgical and nine obstetrical hereditary AT deficiency patients received antithrombin alfa for a mean period of seven days. No clinically overt DVT occurred. Central review of ultrasonograms identified signs of acute DVT in two out of 13 evaluable patients. No antithrombin alfa-related AEs were reported. No patient developed anti-antithrombin alfa antibodies. In conclusion, this study suggests that antithrombin alfa is a safe and effective alternative to human plasma-derived AT for treating hereditary AT deficiency patients at high risk for thromboembolic events.
authors.affiliation: Hannover Medical School, Dept. of Haematology, Haemostasis, Oncology & Stem Cell Transplantation, Germany. tiede.andreas@mh-hannover.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Tiede
authors.forename: R Campbell
authors.initials: RC
authors.lastname: Tait
authors.forename: Don W
authors.initials: DW
authors.lastname: Shaffer
authors.forename: Francesco
authors.initials: F
authors.lastname: Baudo
authors.forename: Bernard
authors.initials: B
authors.lastname: Boneu
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Dempfle
authors.forename: Marie Helene
authors.initials: MH
authors.lastname: Horellou
authors.forename: Robert
authors.initials: R
authors.lastname: Klamroth
authors.forename: John
authors.initials: J
authors.lastname: Lazarchick
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Mumford
authors.forename: Sam
authors.initials: S
authors.lastname: Schulman
authors.forename: Caroline
authors.initials: C
authors.lastname: Shiach
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Bonfiglio
authors.forename: Johan T M
authors.initials: JT
authors.lastname: Frieling
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Conard
authors.forename: Mario
authors.initials: M
authors.lastname: von Depka
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D000991:Antithrombins / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency / Q000235:genetics; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects; D025861:Blood Coagulation Disorders, Inherited / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D002585:Cesarean Section / Q000009:adverse effects; D036861:Delivery, Obstetric / Q000009:adverse effects; D004334:Drug Administration Schedule; D005060:Europe; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D016462:Mammaplasty / Q000009:adverse effects; D008875:Middle Aged; D010690:Phlebography; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors; D016896:Treatment Outcome; D018616:Ultrasonography, Doppler, Duplex; D014481:United States; D020246:Venous Thrombosis / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D000991:Antithrombins; D011994:Recombinant Proteins; D006493:Heparin