Continuous infusion of coagulation factor products.
OBJECTIVE
To review clinical information related to the use of continuous infusion factor products in patients with hemophilia. Specifically, case reports and open-label trials are summarized involving the use of factor VIII and recombinant factor VIIa for a variety of indications including surgical prophylaxis, acute bleeding, primary prevention, and management of inhibitors. In addition, issues surrounding the use of continuous infusion of factor products such as pharmacokinetic rationale, stability/sterility, and cost are reviewed.


METHODS
Primary and review articles were identified through a MEDLINE search (1990-June 2001) and through secondary sources.


METHODS
All articles identified from the data sources were evaluated, and all information deemed relevant was included in this review.


RESULTS
Data concerning the administration of factor products are primarily detailed in open-label trials and case reports. Comparisons between intermittent bolus injections and continuous infusion of factor products are limited and primarily compare continuous infusion regimens with historical controls. The rationale behind the continuous-infusion approach is linked to the pharmacokinetics of factor products administered via this route. Pharmacokinetic data reveal that, with continuous infusion of factor products, a reduction in clearance and a maintenance of factor serum concentrations are noted.


CONCLUSIONS
Administration of factor products (factor VIII and recombinant factor VIIa) via continuous infusion has produced favorable hemostatic effects compared with intermittent bolus injections. The advantages of continuous infusion include maintenance of a constant factor concentration, thereby reducing risk of bleeding from excessively low trough concentrations, and a decrease in factor consumption related to a reduction in factor clearance with constant infusion. Manufacturers recommend using reconstituted factor products either immediately or within 1-3 hours after reconstitution; however, several studies have found the products to be stable and sterile for longer periods.
Stachnik
Joan M
JM
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, 833 S. Wood Street (M/C 886), Rm. 164, Chicago, IL 60612-7230, USA. stachnik@uic.edu
Gabay
Michael P
MP
D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005167:Factor VII / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D005169:Factor VIII / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015942:Factor VIIa; D006467:Hemophilia A / Q000188:drug therapy*; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D007260:Infusion Pumps / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D001779:Blood Coagulation Factors; D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa