ABSTRACT
INTRODUCTION: Recombinant factor IX fusion protein (rIX-FP) has been developed to improve the pharmacokinetic (PK) profile of factor IX (FIX), allowing maintenance of desired FIX activity between injections at extended intervals, ultimately optimizing haemophilia B treatment. AIM: To determine the efficacy and safety of rIX-FP in the perioperative setting. METHODS: Subjects were adult and paediatric patients with severe to moderately severe haemophilia B (FIX ≤ 2%) participating in three Phase III clinical trials and undergoing a surgical procedure. PK profiles were established prior to surgery for each patient. Haemostatic efficacy was assessed by the investigator for up to 72 h after surgery. Safety measurements during the study included adverse events and inhibitors to FIX. FIX activity was monitored during and after surgery to determine if repeat dosing was required. RESULTS: Twenty-one, both major and minor, surgeries were performed in 19 patients. Haemostatic efficacy was rated as excellent (n = 17) or good (n = 4) in all surgeries. A single preoperative dose maintained intraoperative haemostasis in 20 of 21 surgeries. Nine major orthopaedic surgeries were conducted in eight patients with a mean of 7 (range: 6-12) rIX-FP injections during surgery and the 14-day postoperative period. Median rIX-FP consumption for orthopaedic surgeries was 87 IU kg(-1) preoperatively and 375 IU kg(-1) overall. No subject developed inhibitors to FIX or antibodies to rIX-FP. CONCLUSION: Recombinant factor IX fusion protein was well tolerated and effectively maintained haemostasis during and after surgery. Stable FIX activity was achieved with a prolonged dosing interval and reduced consumption compared to conventional or currently available long-acting recombinant FIX.
Subject(s)
Coagulants/therapeutic use , Factor IX/therapeutic use , Hemophilia B/drug therapy , Serum Albumin/genetics , Adolescent , Adult , Child , Factor IX/genetics , Factor IX/metabolism , Half-Life , Hemophilia B/pathology , Hemorrhage/prevention & control , Humans , Middle Aged , Postoperative Period , Preoperative Care , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/pharmacokinetics , Recombinant Fusion Proteins/therapeutic use , Serum Albumin/metabolism , Severity of Illness Index , Surgical Procedures, Operative , Young AdultABSTRACT
In rats a stereotactic electrocoagulation of the Nucleus ventromedialis hypothalami (NVM) leads to a VMH syndrome (ventromedial hypothalamic syndrome) with hyperphagia, adiposity, and hyperinsulinaemia. A less known fact in this connection is the increased secretion of gastric acid (hyperchlorohydria). We could prove that the basal gastric secretion increases after NVM lesions by two times (from 18 mumol H+/hr to 37 mumol H+/hr) and that this hyperchlorohydria can be removed by a vagotomy. From this fact one can derive conclusions concerning the acute gastric mucous secretion after brain lesions with regard to their pathogenesis and therapy.
