In Vivo Inactivation of Antithrombin III Is Promoted by Heparin During Cardiopulmonary Bypass

Abstract

To study the in vivo effect of heparin on antithrombin III (AT3) when elastase is elevated, the blood of 20 patients undergoing cardiopulmonary bypass (CPB) was assayed for elastase and AT3. The model was chosen because CPB is known to increase plasma elastase and the patients were heparinized. The blood of 20 patients undergoing cardiac surgery was assayed for elastase and AT3 one day preoperatively, every half hour during CPB, and one day postoperatively. Elastase increased significantly and AT3 decreased significantly during CPB. There was a direct correlation between the rise in elastase and decrease in AT3. AT3 decreased even further when elastase was elevated and patients were heparinized (AT3/elastase = 0.04 + 0.07), compared with the drop with elevated elastase alone (AT3/elastase = 0.11 + 0.14) (P less than .0015). These data indicate that (1) CPB is associated with an increase in plasma elastase, (2) elevated plasma elastase is associated with a reduction in AT3, and (3) heparin promotes the inactivation of AT3 when serum elastase is increased. These data confirm the in vitro observation that heparin accelerates the inactivation of AT3 in the presence of elastase.

Comparison of two infusion rates of antithrombin concentrate in cardiopulmonary bypass surgery

“…Enoxaparin is the only LMWH compound to have demonstrated sustained clinical and economic benefits in comparison with UFH in the management of unstable angina/non-ST-segment elevation myocardial infarction (NSTEMI). 22 The use of preoperative dalteparin or anti-Xa did not predict a need for extra heparin to achieve target ACT, neither correlated to low/high TAT nor lowered baseline plasma levels of antithrombin, corroborating the finds of Linden, et al 10 All our patients with a baseline anti-Xa activity > 3 IU/ml had a prolonged baseline ACT. ACT is sensitive to IV dalteparin at clinically relevant doses during PCI.…”

“…8 The increased levels of elastase seen during CPB may also contribute to a decreased concentration of AT intraoperatively. 10 AT supplementation during CPB to optimize ACT or plasma AT levels has been used successfully. 11 A recent review by Speiss 1 comparing studies of AT and FFP to treat HR during CPB (defined as inadequate prolongation of ACT) found 11 reports favouring AT, but only 5 favouring FFP.…”