THROMBIN REGULATION IN CONGENITAL HEART-DISEASE AFTER CARDIOPULMONARYBYPASS OPERATIONS

Children with cyanotic congenital heart disease who undergo operation with cardiopulmonary bypass are at increased risk of thromboembolic or hemorrhagic complications, or both. Regulation of thrombin, a key enz yme in coagulation, is essential in preventing these complications. We therefore examined the in vitro capacity of plasma from 15 child en w ith cyanotic congenital heart disease to generate thrombin and to inhi bit I-125-thrombin before and after cardiopulmonary bypass. We also as sessed whether thrombin had been generated in vivo by assaying levels of fibrinogen, thrombin-antithrombin III complexes, and D-dimer. Plasm a levels of the thrombin inhibitors, antithrombin III, alpha-2-macrogl obulin, and heparin cofactor II were also measured. Thrombin regulatio n was normal before operation. After cardiopulmonary bypass, the in vi tro capacity to generate thrombin decreased by 50%, and this was prima rily a result of hemodilution (31%). Similar postoperative decreases w ere noted in the levels of antithrombin III, heparin cofactor II, and alpha-2-macroglobulin (26% to 45%). However, the total in vitro plasma thrombin inhibitory capacity decreased by only 13%. Levels of thrombi n-antithrombin III and D-dimer increased after operation, indicating t hat thrombin had been generated and inhibited in vivo. Clinically, the re were no thromboembolic complications although six patients required replacement therapy for excessive small-vessel bleeding. In conclusio n, thrombin regulation is significantly altered after cardiopulmonary bypass. Although thrombin is generated in vivo, the total residual cap acity to do so is impaired because of hemodilution. Despite a concomit ant decrease in thrombin inhibitor levels, the total residual in vitro capacity of plasma to inhibit thrombin is relatively spared. This sug gests that after cardiopulmonary bypass the risk of hemorrhagic compli cations after an additional hemostatic challenge is relatively greater than the risk of thrombotic complications. This might be reflected in the predominance of hemorrhagic complications in our patients.