Anticoagulation and anticoagulation reversal with cardiac surgery involving cardiopulmonary bypass: An update

Accelerated thrombin generation is central to the development of hemostatic abnormalities during cardiopulmonary bypass (CPB) that are associated with both thromboembolic complications and serious, abnormal breeding. Thrombin not only converts fibrinogen to fibrin, but also activates platelets and c oagulation factors V, VIII, and XI and causes release of von Willebrand fac tor from vascular endothelium. Thrombin can also downregulate the hemostati c system by inducing formation of platelet inhibitory agents, such as nitri c oxide and prostacyclin, and release of tissue plasminogen activator, faci litating activation of protein C, and releasing tissue factor pathway inhib itor. Excessive thrombin activity may also result in substantial consumptio n of platelets, fibrinogen, and labile coagulation factors and abnormal ble eding. Elevated tissue plasminogen activator levels secondary to activation of the contact system and surgery catalyze the formation of plasmin, which also consumes or internalizes platelet glycoprotein receptors and coagulat ion factors V,VIII, and fibrinogen. Heparin can reduce the generation of an d mediate neutralization of excessive and CPB-associated thrombin activity. Heparin anticoagulation is commonly monitored with the activated clotting time (ACT). However, the ACT may be prolonged by factors other than heparin during CPB, such as hemodilution and hypothermia, and therefore may not ac curately reflect the extent of anticoagulation by heparin. Aprotinin, a non specific serine protease inhibitor used with CPB, can also prolong celite-b ased ACT values, rendering it less reliable for monitoring heparin anticoag ulation. Therefore, several alternative anticoagulation strategies have bee n recommended when aprotinin is used, such as a higher celite ACT trigger ( >750 seconds), monitoring of whole brood heparin concentrations (eg, >2.7 U /mL), or administration of heparin based on a CPB duration-dependent, fixed -dose regimen. Administration of heparin doses higher than those generally recommended, as guided by predetermined, patient-specific whole blood hepar in concentration measurements during bypass, can reduce excessive thrombin- mediated consumption of platelets and coagulation factors as well as post-C PB blood loss and blood component transfusions. New modalities of improving suppression of excess thrombin generation during CPB include use of hepari n-bonded CPB circuits, heparin cofactor If or related analogs, supplemental antithrombin ill, direct thrombin inhibitors (eg, hirudin, argatroban), an d inhibitors of the contact and tissue factor pathways. The safety and effi cacy of these approaches remains to be established by additional, appropria tely powered, prospective studies. Copyright (C) 1999 by W.B. Saunders Comp any.