Thrombin During Cardiopulmonary Bypass L. Henry Edmunds, MD, Robert W. Colman, MD  The Annals of Thoracic Surgery  Volume 82, Issue 6, Pages 2315-2322 (December 2006) DOI: 10.1016/j.athoracsur.2006.06.072 Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Diagram illustrates the five pathways for generation of thrombin during cardiopulmonary bypass (CPB) and open heart surgery (OHS). The protein or proteins that start each pathway appear at the top of the diagram. Plus signs (+) designate the principal substrate, and arrows show the enzyme produced by the reaction. The contact pathway (far left) is initiated by activation of factor XII, which with cofactors high molecular kininogen (HK) and pre-kallikrein (PK) activates factor XI to factor XIa. Thrombin, once produced, also directly activates factor XI. Factor XIa activates factor IX in the next reaction, which forms part of the intrinsic tenase complex. Although animal studies indicate that factor XIIa activates factor VII, this pathway has not been studied in patients with OHS and CPB. Both cellular tissue factor (TF) and soluble plasma tissue factor (pTF) activate factor VII in the extrinsic coagulation pathway to form the factor VIIa/tissue factor complex or extrinsic tenase. pTF requires a phospholipid cofactor (monocyte, platelet or microparticle). Extrinsic tenase activates both factors IX and X. Activated factor IX (factor IXa) complexes with thrombin activated factor VIII to form intrinsic tenase, which activates factor X. Tissue factor pathways and extrinsic tenase initiate thrombin formation, but once begun, the intrinsic coagulation pathway, aided by activated platelets, is the dominate source of factor Xa. Factor Xa with factor Va forms prothrombinase, which cleaves prothrombin to form α-thrombin and prothrombin fragment, F1.2. The Annals of Thoracic Surgery 2006 82, 2315-2322DOI: (10.1016/j.athoracsur.2006.06.072) Copyright © 2006 The Society of Thoracic Surgeons Terms and Conditions