An ideal outcome in surgical procedures is achievement of adequate hemostasis without excessive bleeding despite transection of numerous blood vessels, a necessary part of any surgical procedure. Meticulous attention to securing intraoperative hemostasis is the surgeon's responsibility. The postoperative hemostatic response to injury must not lead to a hypercoagulable state and thrombosis because it also is accompanied by stasis and vessel injury, fulfilling Virchow's triad. Maintenance of a proper balance between the need for hemostasis but absence of pathologic thrombosis requires fine-tuning. There are many factors influencing this balance to determine the outcome: (1) the presence of inherited and acquired factors that predispose to bleeding or thrombosis; (2) preoperative and intraoperative events; (3) the health of vital organs, including the vascular tree; and (4) the underlying disease state. For discussion of prophylaxis and treatment of venous thromboembolic disease and postcardiac surgical bleeding, the reader is referred to other articles. This article discusses selected conditions leading to postoperative bleeding.

A brief overview of hemostasis is provided here. The ultimate goal of activation of hemostasis is the generation of thrombin, which leads to formation of a clot at the site of injury. Physiologically, only trace levels of factor VIIa (approximately 1%), the active form of factor VII, are found in the circulation.<sup>20 Morrissey J.H. Tissue factor and factor VII initiation of coagulation Hemostasis and Thrombosis: Basic Principles and Clinical Practice Philadelphia: Lippincott Williams & Wilkins (2001).  89-101

Cliquez ici pour aller à la section Références</sup> Both forms complex with released tissue factor (TF). Current concepts support the view that in vivo, the activation of factor X to factor Xa and factor IX to factor IXa by the active complex of TF–factor VIIa (tenase of the extrinsic pathway) is the key reaction leading to thrombin generation in most disease states. TF also complexes with inactive factor VII; factor VII in the TF–factor VII complex is activated by many serine proteases, including thrombin (IIa); factors Xa, IXa, and XIIa; and plasmin, and by autoactivation by the TF–factor VIIa complex. The amount of thrombin generated by the TF–factor VIIa pathway initially is small but is amplified when factor IX is activated, emphasizing the important contribution of factor IX activation to hemostasis. TF is a glycosylated membrane protein present in cells surrounding the vessels, organs, and skin. The human brain, kidney, and placenta are particularly rich in TF. Endothelial cells and smooth muscle cells do not express TF under normal circumstances. These cells, along with circulating monocytes, tissue macrophages, and fibroblasts, are stimulated by serine proteases, cytokines, and inflammatory mediators to produce TF. Atheromas contain TF that when exposed to blood binds factor VII or factor VIIa. The vitamin K–dependent γ-carboxyglutamic acid residues present on vitamin K–dependent factors (VII, IX, X, and II) are essential for calcium binding, which serves as a bridge for protein binding to phospholipid surfaces for efficient, cell surface–mediated reactions to occur. The major targets for TF pathway inhibitor (TFPI) produced by endothelial cells are factor VIIa and factor Xa, with resultant inhibition of activation of factor X and factor IX; TFPI tightly regulates TF-induced activation of hemostasis.

The intrinsic pathway is activated by contact with a foreign surface or damaged endothelium, leading to activation of factor XII; factor XIIa activates factor XI. Factor XIa activates factor IX independent of the TF–factor VII complex pathway. Activation of contact factors is associated with kinin generation and hypotension. C1-inhibitor controls contact activation, and many serine protease inhibitors, including ⍺₁-proteinase inhibitor (⍺₁-antitrypsin) and protease nexin-2, regulate factor XIa. The tenase complex of the intrinsic pathway, consisting of factor IXa, factor VIIIa, phospholipid, and calcium, converts factor X to factor Xa. Activation of factor X to factor Xa by the extrinsic or intrinsic pathways is the start of the common pathway of coagulation. When factor Xa is generated, it complexes with factor Va, phospholipid, and calcium to form the prothrombinase complex, which converts factor II to factor IIa. Antithrombin is the principal physiologic inhibitor of several serine proteases of coagulation; heparin cofactor II is another endogenous inhibitor of thrombin.

Thrombin generated by activation of the extrinsic or intrinsic pathways has several actions (see Box 1); its primary substrate is fibrinogen, which is converted to fibrin.<sup>25 Swords J.N., Mann K.G. Thrombin Hemostasis and Thrombosis: Basic Principles and Clinical Practice Philadelphia: Lippincott Williams & Wilkins (2001).  171-189

Cliquez ici pour aller à la section Références</sup> Factor XIIIa, generated by the action of thrombin on factor XIII, cross-links the fibrin polymer, which becomes resistant to fibrinolysis. Thrombin also activates factors V and VIII, generating factors Va and VIIIa, which are cofactors for factors Xa and IXa. Thrombin is a potent platelet-aggregating agent, recruiting platelets that provide the cell surface during clot formation. Thrombin binds to thrombomodulin on the endothelial cell; this complex loses the procoagulant actions of thrombin but unmasks its anticoagulant effect by activating protein C, which in the presence of protein S degrades factors Va and VIIIa; this path provides for regulatory control of thrombin's procoagulant functions. Thrombin modulates fibrinolysis by activating thrombin-activatable fibrinolytic inhibitor (TAFI), which impairs fibrinolysis by removing lysine-binding sites from fibrin, crucial for plasminogen binding. Thrombin also releases tissue-type plasminogen activator (t-PA) from endothelial cells, promoting fibrinolysis. The conversion of plasminogen to plasmin by t-PA and urokinase-type plasminogen activator (u-PA) results in activation of the fibrinolytic system. Kallikrein and factor XIIa, components of the contact system, cleave plasminogen, although at a much slower rate than t-PA and u-PA. The actions of plasmin are discussed in the section on fibrinolytic agents and in Box 2

The anticoagulant functions of the endothelium play an important role in determining the outcome of any thrombogenic stimulus. As mentioned previously, thrombin bound to endothelial thrombomodulin loses its procoagulant functions and becomes a powerful anticoagulant by activating protein C. Heparan sulfate proteoglycans (HSPGs) present on the endothelial cell surface and vessel wall matrix, bind antithrombin (AT), and inactivate thrombin; HSPG-bound AT also inhibits factor Xa. Thrombin-induced or other damage to endothelium releases nitric oxide (NO), prostacyclin (PGI₂), and adenosine diphosphatase (ADPase), all of which inhibit platelet function. Circulating plasminogen binds to endothelial cells, where it can be activated easily. Endothelial cells synthesize and release t-PA and u-PA in response to thrombin and other stimuli, activating fibrinolysis and promoting fibrin degradation at the site of vessel injury and clot formation. In sepsis, there is loss of anticoagulant functions of the endothelium. Endotoxin, cytokines, and other inflammatory mediators (tumor necrosis factor [TNF], interleukin [IL]-1) stimulate endothelial cells to release TF, plasminogen activator inhibitor type I (PAI-1), and von Willebrand's factor (vWF) and to decrease synthesis and cell surface expression of thrombomodulin; all of these effects support thrombus formation. Studies suggest heterogeneity not only of endothelial cells from different vascular beds, but also in vascular bed–specific hemostasis. Derangements of this complex system that regulates normal hemostasis can lead to thrombosis or hemorrhage.