Evaluation of factor VIII pharmacokinetics in hemophilia-A subjects undergoing surgery and description of a nomogram for dosing calculations.

Abstract

The pharmacokinetics of factor VIII were studied in a series of 20 hemophilia-A patients undergoing surgery. Regardless of the type of operation, elimination of factor VIII was shown to be increased only in ten cases (50%) during the post-operative period. In this subgroup of patients, factor VIII 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 VIII can be of value in reducing the risk of hemorrhage in these subjects and in exposing other subjects with no postoperative increase in factor VIII clearance to less of the deficient factor. Data from 20 subjects were analyzed to construct a nomogram allowing individualized prediction of factor VIII dosing requirements. The nomogram, which is based on the "single point after a single dose" method, uses a value of factor VIII concentration measured at 10 hr after preoperative loading dose to predict the regimen producing the desired average steady-state concentration of factor VIII (30, 60, or 90 units/dl).