ANTITHROMBIN-III DURING CARDIAC-SURGERY - EFFECT ON RESPONSE OF ACTIVATED CLOTTING TIME TO HEPARIN AND RELATIONSHIP TO MARKERS OF HEMOSTATIC ACTIVATION

This study was designed to determine if, and to what extent, antithrom bin III (AT) levels affect the response of the activated clotting time (ACT) to heparin in concentrations used during cardiac surgery, and t o characterize the relationship between AT levels and markers of activ ation of coagulation during cardiopulmonary bypass (CPB). After inform ed consent, blood specimens obtained from eight normal volunteers (Pha se I) were used to measure the response of the kaolin and celite ACT t o heparin after in vitro addition of AT (200 U/dL) and after dilution with AT-deficient plasma to yield AT concentrations of 20, 40, 60, 80, and 100 U/ dL. In Phase II, blood specimens collected before the admi nistration of heparin and prior to discontinuation of CPB, were used t o measure the response of the kaolin ACT to heparin (preheparin only), AT concentration, and a battery of coagulation assays in 31 patients undergoing repeat or combined cardiac surgical procedures. In Phase I, strong linear relationships were observed between kaolin (slope = 1.0 4 AT -2, r(2) = 0.78) and celite (slope = 1.36 AT + 6, r(2) = 0.77) AC T slopes and AT concentrations below 100 U/dL. In the pre-CFB period o f Phase II, only factors V (partial r = -0.49) and VIII (partial r = - 0.63) were independently associated with heparin-derived slope using m ultivariate analysis; an inverse relationship was observed between AT and fibrinopeptide A levels (r = -0.41) at the end of CPB. Our finding s indicate that the responsiveness of whole blood (ACT) to heparin at the high concentrations used with CPB is progressively reduced when th e AT concentration decreases below 80 U/dL. Because AT is variably, an d sometimes extensively, reduced in many patients before and during CF B, AT supplementation in these patients might be useful in reducing ex cessive thrombin-mediated consumption of labile hemostatic blood compo nents, excessive microvascular bleeding, and transfusion of blood prod ucts. Implications: Heparin, a drug with anticoagulant properties, is routinely given to patients undergoing cardiac surgery to prevent clot formation within the cardiopulmonary bypass circuit. However, when le vels are reduced, heparin is not as effective. Findings within this st udy indicate that administration of antithrombin III may help to prese rve the hemostatic system during cardiopulmonary bypass.