A PRELIMINARY STUDY OF A NEW APROTININ ASSAY

Abstract

Introduction: Aprotinin is effective in reducing bleeding and transfusion requirements in cardiac surgery, but it is an expensive drug. [1] Most patients receive one of two fixed dose regimens of aprotinin based on the Hammersmith protocol. [1] Consequently, patients may be receiving too much or too little aprotinin. A simple assay of aprotinin concentration would allow development of a more effective dose regimen that may improve patient care and reduced institutional costs Methods: Following IRB approval and verbal informed consent, 30 cardiac surgery patients were studied. Ten patients received a full Hammersmith dose regimen. Ten patients received half Hammersmith dose regimen and ten patients did not3 receive aprotinin. The new aprotinin assay measures the ability of aprotinin to inhibit plasmin. Dilute plasma samples were incubated with added 10 [micro sign]l (1 unit/ml) plasmin for 30 minutes. The substrate 20 [micro sign]l 1mM Benzoyl-phe-val-Arg-pNA was added to the sample, and the activity of plasmin was read over 10 minutes at A405-490. Samples were collected at: baseline (1), after loading dose (2), 5 minutes on bypass (3), 30 minutes on bypass (4), 60 minutes on bypass (5), at termination of aprotinin (6), 1 hour after aprotinin infusion termination (7), 4 hours after bypass (8), and 24 hours after bypass (9). Correlations by Pearson's product-moment correlation coefficient. Statistical significance p <or=to 0.05. Results: Large variation in plasma aprotinin concentration occurred over time during aprotinin infusion (Left Figure 1). Most patients receiving half dose aprotinin had plasma concentration less than 200 KIU/ml. There was a significant correlation between patient weight and plasma aprotinin concentration (r2 = 0.49)(Right Figure 1).Figure 1Discussion: These aprotinin concentrations were similar to those previously reported during cardiac surgery. [2] There was large variation in aprotinin concentration with each patient over time and between patients based upon body weight. Patients with half Hammersmith dose regimen rarely achieved 200 KIU/ml concentration, the concentration that inhibits endogenous plasmin.

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