title: Successful hip arthroplasty in an adult male with severe factor XI deficiency using Hemoleven®, a factor XI concentrate.
abstract: Severe factor XI (sFXI) deficiency is a rare bleeding disorder (RBD). FXI replacement is most often required for surgical hemostasis. Plasma, the sole US treatment option, is often complicated by life-threatening allergic reactions. In such circumstances, the FDA offers a mechanism for institution-industry collaboration to facilitate limited use of replacement products licensed abroad. A 58 years old man with sFXI deficiency, required hip replacement. In the past, he received prophylactic plasma for thyroidectomy and experienced a severe allergic reaction. A single use institutional IND FDA application was initiated in collaboration with LFB (Les Ulis, France) to access Hemoleven®, a plasma-derived FXI concentrate. The application required an investigator-initiated IRB-approved protocol for treatment and safety/efficacy monitoring that included: preoperative thrombophilia, FXI inhibitor and pharmacokinetic (PK) evaluations; peri- postoperative administration of ≤ 4 doses of 10-15 U/kg Hemoleven® ; DIC monitoring; postoperative thromboprophylaxis; observation for product efficacy and potential complications. PK study demonstrated the expected 1.8% FXI recovery per U/kg with half-life of 62 hours. Mild D-Dimer elevation was noted 6-9 hours post-infusion. The initial dose (15 U/kg) was administered 15 hours before surgery; subsequently, 3 doses (10 U/kg) were infused every 72 hours. Hemostasis was excellent. No complications were observed. Collaboration allowed for successful patient access to Hemoleven® with excellent PK, safety, and efficacy. This case underscores the need for additional efforts to ensure safe and effective licensed replacement therapies for RBD patients.
authors.affiliation: Department of Pediatrics Hematology/Oncology, Weill Cornell Medical College, New York, NY, USA. santoro@bce.uniroma1.it
authors.forename: C
authors.initials: C
authors.lastname: Santoro
authors.forename: I
authors.initials: I
authors.lastname: Goldberg
authors.forename: F
authors.initials: F
authors.lastname: Bridey
authors.forename: M P
authors.initials: MP
authors.lastname: Figgie
authors.forename: D
authors.initials: D
authors.lastname: Karila-Israel
authors.forename: K
authors.initials: K
authors.lastname: Haviland
authors.forename: C R
authors.initials: CR
authors.lastname: Mackenzie
authors.forename: D M
authors.initials: DM
authors.lastname: Dimichele
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000379:methods; D016063:Blood Loss, Surgical / Q000517:prevention & control; D005172:Factor XI / Q000627:therapeutic use*; D005173:Factor XI Deficiency / Q000188:drug therapy*; D006488:Hemostasis, Surgical / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D005172:Factor XI