Anticoagulation and reversal for cardiopulmonary bypass

Published on 07/02/2015 by admin

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Last modified 07/02/2015

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Anticoagulation and reversal for cardiopulmonary bypass

Brian S. Donahue, MD, PhD

Anticoagulation during cardiopulmonary bypass

The surfaces of the cardiopulmonary bypass (CPB) circuit are highly thrombogenic and readily activate the coagulation cascade when blood comes in contact with them. To prevent thrombus formation, thrombin generation, and coagulation factor consumption, anticoagulation must be initiated prior to, and sustained during, CPB.

Heparin

Heparin (MW 750-1000 kDa) is a glycosaminoglycan, or mucopolysaccharide, composed of alternating D-glucuronic N-acetyl-D-glucosamine acid residues. Heparin has one of the highest negative charge-to-size ratios of any known biologic compound. Heparan sulfate is a related biologic compound that has fewer sulfate groups than heparin and, therefore, has less potency. Heparin inhibits coagulation by serving as a catalyst—antithrombin III (AT) binds to its surface, inducing a conformational change in AT, making its active site more accessible to any of several proteases involved in the intrinsic and common coagulation pathways (thrombin [IIa], factor Xa, factor XIa, factor XIIa, and factor IXa). However, the anticoagulant effects of heparin are primarily mediated by the inhibition of thrombin and factor Xa that occurs when thrombin and factor Xa are bound by AT. Once these covalent bonds are established, the heparin moiety is released and available to bind to another molecule of AT. Heparin also induces the release of tissue factor pathway inhibitor from intravascular endothelium. Fragments of tissue factor pathway inhibitor may contribute to post-CPB coagulopathy.

Administration and monitoring of heparin during cardiopulmonary bypass

Heparin is administered intravenously as a bolus dose of 300 to 400 units/kg. Traditionally, the extent of inhibition of coagulation has been monitored using the whole-blood activated clotting time (ACT). With this technique, the patient’s blood is mixed in a test tube with an activator (e.g., diatomite or kaolin), and the time until clot forms is recorded as the ACT. Although practice varies markedly, most surgeons require an ACT of 400 to 450 sec before they will allow initiation of CPB; however, these limits were established with very little data. The ACT is widely used because it has several advantages: the prolongation of the ACT is generally linear with the heparin level, and the test is widely available, is inexpensive, is easy to perform, and has stood the test of time. However, the ACT has many drawbacks—there is wide variability not only between tests of blood run on different instruments, but also between aliquots of the same blood run on the same instrument. Other methods of anticoagulation monitoring include the measurement of heparin concentration by protamine titration, high-dose thrombin time, and the heparin concentration test. The most popular of these non-ACT methods is the heparin-concentration test, which has been compared with the ACT in efforts to arrive at the most optimal evidence-based management. In a few randomized trials, the heparin-concentration test, compared with the ACT, was found to be associated with greater suppression of the coagulation pathway, decreased perioperative transfusion requirements, and greater total heparin dosing. Overall, a 2006 best-evidence review of point-of-care coagulation testing during CPB concluded that using the heparin-concentration test results in higher heparin and lower protamine dosing, with possible sparing of coagulation system activation and decreased transfusion requirements.

Problems associated with the use of heparin

Heparin-induced thrombocytopenia

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