Pathophysiology and Treatment of Coagulopathy in Massive Hemorrhage and Hemodilution

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Abstract
IN patients with trauma and those who undergo major surgery, multiple breaches of vascular integrity result in bleeding, and in some cases, exsanguination. Fluid (volume) replacement with crystalloids or colloids is usually the initial measure to stabilize systemic circulation by compensating for hypovolemia. When the blood loss is considered major (hemoglobin concentration below 6-10 g/dl),1 erythrocyte (RBC) concentrates are transfused to sustain hemoglobin levels (i.e. , oxygen-carrying capacity). The transfusion of ten or more erythrocyte units (i.e. , replacement of one blood volume) within 24 h is generally considered as massive transfusion in adults.2 Other arbitrary definitions include six or more erythrocyte units within 12 h and over 50 units of blood product use within 24 h, including erythrocytes, platelet concentrates, and fresh frozen plasma (FFP).3,4 There are differences in the initial pathophysiology of coagulopathy between trauma and major surgery, which can be attributed in part to the mechanism of vascular injury, extent of hemorrhage, type of fluid resuscitation, and prophylactic use of antifibrinolytic therapy.5–8 However, hemostatic defects based on conventional laboratory data are often indistinguishable between trauma and major surgery after massive transfusion. Unlike congenital bleeding disorders that are due mostly to a single factor deficiency (e.g. , hemophilia, afibrinogenemia), coagulopathy encountered in trauma and major surgery is of a multifactorial nature. All elements in coagulation, including procoagulant, anticoagulant, fibrinolytic, and antifibrinolytic proteins, exhibit various degrees of deficiency. Although this topic has been reviewed recently by others,5,8,9 the mechanism of coagulopathy related to massive transfusion and hemodilution is not fully understood. In this review, we focus on the effects of hemodilution on thrombin generation, fibrin polymerization, and fibrinolysis, using experimental results as well as existing clinical data to shed light on the mechanisms of dilutional coagulopathy. In addition, we discuss various therapeutic approaches and their clinical implications.