ABSTRACT
Acquired haemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against human factor VIII (hFVIII). OBI-1 is an investigational, B-domain deleted, recombinant FVIII, porcine sequence, with low cross-reactivity to anti-hFVIII antibodies. Efficacy can be monitored with FVIII activity levels in addition to clinical assessments. This prospective, open label, phase 2/3 study was designed to evaluate the efficacy of OBI-1 treatment for bleeding episodes in subjects with AHA. After an initial dose of 200 U kg(-1) , OBI-1 was titrated to maintain target FVIII activity levels, in correlation with clinical assessments, throughout the treatment phase. All 28 subjects with AHA had a positive response to OBI-1 treatment 24 h after initiation despite inhibition of FVIII activity levels immediately after infusion in 10 subjects with baseline anti-porcine FVIII inhibitors. Control of the qualifying bleed was ultimately achieved in 24 of 28 subjects. No related serious adverse events, thrombotic events, allergic reactions or thrombocytopaenia occurred. The results of this study indicate that OBI-1 is safe and effective in treating bleeding episodes in subjects with AHA. The ability to safely and effectively titrate dosing based on FVIII activity levels in this study demonstrates that OBI-1 fulfils the unmet medical need to monitor the key coagulation parameter in AHA patients.
Subject(s)
Factor VIII/therapeutic use , Hemophilia A/drug therapy , Recombinant Proteins/therapeutic use , Adult , Aged , Aged, 80 and over , Animals , Antibodies, Neutralizing , Autoantibodies/immunology , Cross Reactions/immunology , Factor VIII/administration & dosage , Factor VIII/adverse effects , Factor VIII/immunology , Female , Hemophilia A/immunology , Humans , Male , Middle Aged , Recombinant Proteins/administration & dosage , Recombinant Proteins/adverse effects , Recombinant Proteins/immunology , Swine , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Thrombophlebitis (TP) is a frequent complication of the intravenous application of injection anaesthetics. We investigated the influence of different arm positions on the incidence of such a complication in patients undergoing shoulder arthroscopy. PATIENTS AND METHODS: This prospective, randomised study was done in 86 consecutive major shoulder arthroscopies. In order to evaluate the influence of different arm positions, the arm not operated on was positioned either cranial (n = 31) or caudal (n = 55) to the level of the right atrium. The number of TP in the 5 days following the arthroscopy was detected clinically and proven by ultrasound studies. RESULTS: 8 TP occurred in the group of patients with caudal arm positioning and none in the other group. Statistically, the incidence of TP was not associated with the weight or the height of the patients nor with the duration of the anaesthesia or the doses of anaesthetics used in each patient (p < 0.05). CONCLUSION: An elevated position of the arm used for anaesthesia during shoulder arthroscopy is suggested in order to prevent TP.
