Is Heparin the Ideal Anticoagulant for Cardiopulmonary Bypass? Dermatan Sulphate May Be an Alternate Choice

Abstract

SummaryPerformance of cardiopulmonary bypass (CPB) during cardiac surgery requires the administration of high dose heparin to prevent CPB pump occlusion. However, this heparin use is associated with bleeding side-effects. Moreover, at the end of CPB, the heparin must be neutralized with protamine sulphate, which is also associated with adverse side-effects. A number of recent studies suggest that dermatan sulphate may be useful as an alternate anticoagulant to heparin. We determined whether CPB could be performed using dermatan sulphate instead of heparin, in an adult pig CPB model. When heparin was used, a high dose (> 200 U/kg, which generated > 3 anti-thrombin U/ml of plasma), was required to perform successful CPB and to maintain CPB pump patency. This dose was associated with a post CPB bleeding of ≈ 600 ml/2h. in contrast, successful CPB could be achieved when the pigs were given lower doses of dermatan sulphate than heparin, which in turn, were associated with less bleeding. We conclude that dermatan sulphate may be an alternate anticoagulant for cardiac surgery

Heparin Ablates Force Development during Platelet Mediated Clot Retraction

“…The failure to completely reverse heparin's antiplatelet effects may play a role in the platelet dysfunction associated with cardiopulmonary bypass. The ability to detect and quantify heparin antiplatelet effects may enhance our understanding of heparin's therapeutic action, and may allow better comparison of heparin with other potential antico agulants such as dermatan sulfate (29).…”

Newer Strategies for the Treatment of Heparin‐Induced Thrombocytopenia

“…Heparin is the universally accepted anticoagulant during cardiopulmonary bypass (CPB). Although it is not an ideal agent (it is now recognized that thrombin generation occurs progressively during CPB despite the high concentrations used 82 ), it has several important advantages, including simplicity of anticoagulant monitoring (activated clotting time) or aPTT and rapid reversal (neutralization) of its anticoagulant effects with protamine (1 mg neutralizes about 100 U USP).…”

Anticoagulants and Extracorporeal Circuits

“…When thrombin binds to plasma pro teins at a surface, it undergoes a conformational shape change, which renders thrombin resistant to inhibition by heparin/antithrombin. 11,12 However, DS also inhibits clot-bound thrombin through heparin cofactor II. 11,12 DS still has less effect on overall coagulation, and has less effect on platelet function as compared with SH in ani mal experiments.…”

“…11,12 However, DS also inhibits clot-bound thrombin through heparin cofactor II. 11,12 DS still has less effect on overall coagulation, and has less effect on platelet function as compared with SH in ani mal experiments. 13 Two dose-finding studies as well as current developments using DS in CPB will be discussed in this review.…”