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Thrombin and Cardiopulmonary Bypass – A Paradigm for Evaluation of the Regulation of Hemostasis

  • Review Article
  • Published:
International Journal of Angiology

Abstract

Extracorporeal circulation for the purpose of cardiopulmonary bypass (CPB) is used extensively for repair of cardiac defects. Complex mechanisms, many of which involve the generation of thrombin, are initiated by the institution of CPB. Thrombin is generated during CPB in spite of high doses of heparin. The tissue factor/factor VII pathway is also activated and is probably responsible for generation of most of the thrombin seen during CPB. Plasma proteins (humoral phase) along with platelets, endothelium and white cells (cellular phase) are also activated by contact of blood with synthetic surfaces. Small amounts of thrombin activate endothelial cells which then generate tissue plasminogen activator (t-PA). Plasmin is generated by the action of t-PA and fibrinolysis ensues. The blood becomes a mix of vasoactive substances that alter vascular smooth muscle tone and endothelial cell contraction. The sum of these reactions is called the ‘whole body inflammatory response’ and is responsible for postoperative morbidity including bleeding and organ system dysfunction.

Attempts to control the morbidity of CPB have focused on reversible inhibitors of some of the reactions described above. Potentially helpful new strategies may include: 1) enhanced production of thrombin-activatable fibrinolysis inhibitor (TAFI) to limit fibrinolysis, 2) synthesis of thrombin receptor blockers to limit platelet and endothelial activation, 3) protection of endothelial cell receptors during CPB, 4) control of CPB-induced platelet-PMN and endothelial-PMN adhesion in order to limit postoperative organ system dysfunction, and 5) limitation of tissue factor pathway activation in order to minimize thrombin production during CPB. This review highlights recent developments in the understanding of the molecular mechanisms of the action of thrombin induced by CPB.

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  1. Division of Cardiovascular and Thoracic Surgery, University of Kentucky Chandler Medical Center, Lexington, Kentucky

    Victor A. Ferraris M.D., Ph.D., F.I.C.A. & Suellen P. Ferraris Ph.D.

  2. Department of Surgery, F. Edward Hebert School of Medicine, United States Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

    Victor A. Ferraris M.D., Ph.D., F.I.C.A.

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  2. Suellen P. Ferraris Ph.D.
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Correspondence to Victor A. Ferraris M.D., Ph.D., F.I.C.A..

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Ferraris, V.A., Ferraris, S.P. Thrombin and Cardiopulmonary Bypass – A Paradigm for Evaluation of the Regulation of Hemostasis. Int J Angiol 14, 193–210 (2005). https://doi.org/10.1007/s00547-005-2016-z

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