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J Thorac Cardiovasc Surg 2006;131:515-516
© 2006 The American Association for Thoracic Surgery

Editorial

Anticoagulation for cardiopulmonary bypass: Is a replacement for heparin on the horizon?

Theodore E. Warkentin, MD *

Department of Pathology and Molecular Medicine, and the Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Received for publication November 1, 2005; accepted for publication November 1, 2005.

* Address for reprints: Theodore E. Warkentin, MD, Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences (General Site), 237 Barton St E, Hamilton, Ontario L8L 2X2, Canada (Email: twarken@mcmaster.ca).

The first 20% of the full text of this article appears below.

GoUnfractionated heparin was first used in 1953 for cardiac surgery employing cardiopulmonary bypass (CPB) 1 Go and has remained the standard anticoagulant ever since. This near-monopoly status should not imply ideal drug properties. Indeed, heparin has several disadvantages: it poorly inhibits fibrin-bound thrombin, and thus thrombin is generated progressively during CPB; its thrombin inhibition is only indirect (via antithrombin) and leads to antithrombin depletion, with potential for adverse consequences 2 Go; and its monitoring (by activated clotting time [ACT]) only roughly estimates anticoagulant effect. Moreover, heparin's antidote, protamine, is itself problematic: its shorter half-life can lead to bleeding (via protamine "rebound") and its foreign structure can trigger life-threatening hypersensitivity reactions.

A largely unexplored issue is whether heparin's large size and strong negative charge, which result in binding to many proteins, are responsible for certain adverse events associated with CPB. Indeed, one protein to which heparin binds is a positively charged chemokine, platelet factor 4 (PF4). The resulting complexes of PF4 and heparin are very immunogenic: detectable antibodies against PF4/heparin complexes develop in as . . . [Full Text of this Article]


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This article has been cited by other articles:


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 Ann. Thorac. Surg.Home page
B. D. Spiess
Treating Heparin Resistance With Antithrombin or Fresh Frozen Plasma
Ann. Thorac. Surg., June 1, 2008; 85(6): 2153 - 2160.
[Abstract] [Full Text] [PDF]


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