American Journal of Hematology 30:140-149 (1989) z Evaluation of Factor VII I P harmacokinetics in Hemop hilia-A Subjects Undergoing Surgery and Description of a Nomogram for Dosing Calculations G. Longo, A. Messori, M. Morfini, F. Baudo, N. Ciavarella, S. Cinotti, E. Filimberti, G. Giustarini, A.C. Molinari, and Pierluigi Rossi Ferrini Centro Ernofilici e Universita di Firenze (G.L., A.M., M.M., S.C., E.F., G.G., P.R.F.), Divisione di Ematologia (F.B.), Ospedale di Niguarda, Milano; Servizio di Coagulazione e Assistenza Ernofilici, Policlinico di Bari (N.C.), and Divisione di Pediatria (A.C.M.), lstituto Gaslini, Genova, Italy The pharmacokinetics of factor Vlll were studied in a series of 20 hemophilia-A patients undergoing surgery. Regardless of the type of operation, elimination of factor Vlll was shown to be increased only in ten cases (50%) during the post-operative period. In this subgroup of patients, factor Vlll half-life, measured immediately after surgery, was considerably shorter (mean = 9.6 hr, n = 10) than that determined in the same individual during the late operative period (mean = 17.8 hr, n = 10). These findings indicate that identification of patients with increased postoperative consumption of factor Vlll can be of value in reducing the risk of hemorrhage in these subjects and in exposing other subjects with no postoperative increase in factor Vlll clearance to less of the deficient factor. Data from 20 subjects were analyzed to construct a nomogram allowing indivi- dualized prediction of factor Vlll dosing requirements. The nomogram, which is based on the “single point after a single dose” method, uses a value of factor Vlll concentra- tion measured at 10 hr after preoperative loading dose to predict the regimen producing the desired average steady-state concentration of factor Vlll(30, 60, or 90 unitsldl). Key words: hemophilia, surgery, factor VIII, pharmacokinetics INTRODUCTION zyxwvutsrq To prevent viral infections as well as protein overload in patients with classic hemophilia, recent data zyxwvu [l-51 indicate that exposure to factor zyxwvuts VIII concentrates should be limited to the minimum amount eliciting adequate clinical response. This present trend emphasizes the need to develop dosing strategies for rationalizing the use of factor VIII concentrates, particularly in those situations in which prolonged high-dose treatments are required. Furthermore, new and very expensive concentrates ob- tained by immunoaffinity chromatography with mono- clonal antibodies or by DNA-recombinant techniques will be used in hemophilia therapy, which also stresses the need for cost-containment strategies. Surgery in hemophiliacs is a clinical situation in which substitution therapy is generally prolonged over 1 week or longer and implies the administration of significant amounts of factor VIII. On the one hand, this increases the patients’ exposure to the deficient factor in terms of overall load of allogenic proteins; on the other hand, the zyxwv 0 1989 Alan R. Liss, Inc. risk of hemorrhage increases when insufficient doses of the deficient factor are administered. In light of these problems, empiric use of concentrates in surgical patients should be discouraged, and research should be performed to devise methods of factor VIII dosing based on phar- macokinetic principles, as recently suggested [6-81. The present study was undertaken to gain information on the pharmacokinetics of exogenous factor VIII in hemophiliacs undergoing surgery and to discuss the pos- sibility of applying pharmacokinetic methods for indivi- dualizing factor VIII dose in these subjects. Received for publication April 15, 1988; accepted October 13, 1988. Address reprint requests to M. Morfini, M . D . , Hemophilia Center, USL 10/D, University of Florence, vide Morgagni 85, 50134 Flor- ence, Italy.