title: Aprotinin prolongs activated and nonactivated whole blood clotting time and potentiates the effect of heparin in vitro.
abstract: This study was designed to evaluate the effect of aprotinin on activated versus nonactivated whole blood clotting time using two different on-site methods and to quantify these anticoagulant properties when compared to heparin in a controlled, in vitro environment. Blood specimens were obtained prior to heparin administration from 56 patients undergoing cardiac surgery. Specimens obtained from the first consecutive 20 patients were mixed with either normal saline (NS) or aprotinin (400 kallikrein inhibiting units (KIU)/mL), inserted into Hemochron tubes 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 clotting time (WBCT1) using four Hemochron instruments. Accordingly, specimens obtained from the second consecutive 20 patients were mixed with either NS or aprotinin, inserted into Automated Clot Timer cartridges 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 whole blood clotting times (WBCT2) using four Automated Clot Timer instruments. 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 were then used for measurement of whole blood clotting time (WBCT2) using six Automated Clot Timer instruments. Aprotinin significantly prolonged activated or nonactivated whole blood clotting time and potentiated the prolongation of whole blood clotting time by heparin. The linear relationship between whole blood clotting time and either heparin concentration (WBCT2 = H x 357 + 280, mean adjusted r2 = 0.88) or aprotinin concentration (WBCT2 = A x 0.97 + 300, mean adjusted r2 = 0.94) was variable among patients. On average, 200 KIU/mL of aprotinin prolonged WBCT2 to the same extent as 0.69 +/- 0.28 U/mL of heparin using linear regression models within each patient. Aprotinin significantly prolongs activated or nonactivated whole blood clotting time measurements in a dose-dependent manner. Since prolongation of whole blood clotting time by heparin is potentiated by aprotinin in vitro, aprotinin's anticoagulant properties may in part account for the prolonged celite activated clotting time values observed in the presence of aprotinin.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Despotis
authors.forename: K S
authors.initials: KS
authors.lastname: Filos
authors.forename: V
authors.initials: V
authors.lastname: Levine
authors.forename: A
authors.initials: A
authors.lastname: Alsoufiev
authors.forename: E
authors.initials: E
authors.lastname: Spitznagel
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D006348:Cardiac Surgical Procedures / Q000379:methods; D007692:Diatomaceous Earth / Q000494:pharmacology; D004357:Drug Synergism; D006490:Hemostatics / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007616:Kaolin / Q000494:pharmacology; D014914:Whole Blood Coagulation Time
chemical_list: D000925:Anticoagulants; D006490:Hemostatics; D007616:Kaolin; D007692:Diatomaceous Earth; D006493:Heparin; D007611:Aprotinin