Alternatives to unfractioned heparin for anticoagulation in cardiopulmonary bypass

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Abstract
Despite the progress made in the development of cardiopulmonary bypass (CPB) equipment, systemic anticoagulation with unfractioned heparin and post-bypass neutralization with protamine are still used in most perfusion procedures. However, there are a number of situations where unfractioned heparin, protamine or both cannot be used for various reasons. Intolerance of protamine can be addressed with extracorporeal heparin removal devices, perfusion with (no) low systemic heparinization and, to some degree, by perfusion with alternative anticoagulants. Various alternative anticoagulation regimens have been used in cases of intolerance to unfractioned heparin, including extreme hemodilution, low molecular weight heparins, danaparoid, ancrod, r-hirudin, abciximab, tirofiban, argatoban and others. In the presence of heparin-induced thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an acceptable solution which has been well studied. The main issue with r-hirudin is the difficulty in monitoring its activity during CPB, despite the fact that ecarin coagulation time assessment is now available. A more recent approach is based on selective blockage of platelet aggregation by means of monoclonal antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors and suppression of platelet aggregation to less than 20% allows the giving of unfractioned heparin and running CPB in a standard fashion despite HIT and thrombosis. Likewise, at the end of the procedure, unfractioned heparin is neutralized with protamine as usual and donor platelets are transfused if necessary. GPIIb/IIIa inhibitors are frequently used in interventional cardiology and, therefore, are available in most hospitals.