title: Adjusted dose continuous infusion of factor VIII in patients with haemophilia A.
abstract: Surgical interventions in patients suffering from haemophilia A require infusions of large doses of factor VIII (F VIII) concentrates. These are expensive and may pose a burden on the immune system, which is already compromised in many haemophiliacs. F VIII is usually given as bolus injections, although there are reports on fixed dose continuous infusion. We have developed a continuous infusion programme with dosage adjusted according to daily calculation of the clearance of F VIII. Twenty-four haemophiliacs received a total of 205 d of continuous infusion with F VIII (168 d in hospital, 37 d home therapy). Eighteen patients underwent surgeries (11 elective, seven emergency) and six were treated for serious haemorrhages. We observed a significant, progressive decrease of the clearance of F VIII over the first 5 d from 3.2 (2.8-3.5) to 1.7 (1.3-1.9) ml/kg/h (median and interquartile range). The decrease of the clearance together with the fact that a continuous infusion requires less drug than bolus injections to keep the same minimal concentration, contributed to much lower doses of F VIII than reported in the literature or than required by historical controls, matched for the type of operation. Other advantages of our method are improved safety with stable activities of F VIII, lack of hazardous troughs below the haemostatic range, and the convenience, which permits ambulant therapy even when high doses of F VIII are required.
authors: Department of Haematology, Sheba Medical Centre, Tel Hashomer, Israel.
authors: U
authors: U
authors: Martinowitz
authors: S
authors: S
authors: Schulman
authors: S
authors: S
authors: Gitel
authors: H
authors: H
authors: Horozowski
authors: M
authors: M
authors: Heim
authors: D
authors: D
authors: Varon
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002648:Child; D004334:Drug Administration Schedule; D005169:Factor VIII / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D008875:Middle Aged; D013514:Surgical Procedures, Operative
chemical_list: D005169:Factor VIII