APROTININ PROLONGS ACTIVATED AND NONACTIVATED WHOLE-BLOOD CLOTTING TIME AND POTENTIATES THE EFFECT OF HEPARIN IN-VITRO

This study was designed to evaluate the effect of aprotinin on activat ed versus nonactivated whole blood clotting time using two different o n-site methods and to quantify these anticoagulant properties when com pared to heparin in a controlled, in vitro environment. Blood specimen s were obtained prior to heparin administration from 56 patients under going cardiac surgery. Specimens obtained from the first consecutive 2 0 patients were mixed with either normal saline (NS) or aprotinin (400 kallikrein inhibiting units (KIU)/mL), inserted into Hemochron(R) tub es containing either NS or heparin (0.3 or 0.6 U/mL) and then used to measure celite-activated (celite ACT) and nonactivated whole blood clo tting time (WBCT1) using four Hemochron(R) instruments. Accordingly, s pecimens obtained from the second consecutive 20 patients were mixed w ith either NS or aprotinin, inserted into Automated Clot Timer(R) cart ridges containing either NS or heparin (0.06, 0.13, or 0.25 U/mL) and then used to measure kaolin-activated (kaolin ACT) or nonactivated who le blood clotting times (WBCT2) using four Automated Clot Timer(R) ins truments. Specimens obtained from the last 16 patients were mixed with either incrementally larger doses of aprotinin (0, 100, 200, 300, or 400 KIU/mL) or heparin (0, 0.12, 0.24, 0.36, 0.48, or 0.72 U/mL) and w ere then used for measurement of whale blood clotting time (WBCT2) usi ng six Automated Clot Timer(R) instruments. Aprotinin significantly pr olonged activated or nonactivated whole blood dotting time and potenti ated the prolongation of whole blood clotting time by heparin. The lin ear relationship between whole blood clotting time and either heparin concentration (WBCT2 = H x 357 + 280, mean adjusted r(2) = 0.88) or ap rotinin concentration (WBCT2 = A x 0.97 + 300, mean adjusted r(2) = 0. 94) was variable among patients. On average, 200 KIU/mL of aprotinin p rolonged WBCT2 to the same extent as 0.69 +/- 0.28 U/mL of: heparin us ing linear regression models within each patient. Aprotinin significan tly prolongs activated or nonactivated whole blood clotting time measu rements in a dose-dependent manner. Since prolongation of whole blood clotting time by heparin is potentiated by aprotinin in vitro, aprotin tn's anticoagulant properties may in part account for the prolonged ce lite activated clotting time values observed in the presence of aproti nin.