Active, personalized, and balanced coagulation management saves lives in patients with massive bleeding.

MASSIVE hemorrhage originates from severe injury of blood vessels caused by major trauma, surgery, underlying medical conditions, or any combination thereof. If not diagnosed and treated readily, patients exsanguinate and die from hypovolemic shock. In this issue of ANESTHESIOLOGY, Bolliger et al. review the mechanisms of coagulopathy in massive hemorrhage with a special emphasis on the hemodilutional effects of fluid therapy on thrombin generation, fibrin polymerization, and fibrinolysis. A proper understanding of the complex pathophysiology of coagulopathy in massive bleeding is essential for effective treatment. The coagulation system represents a delicate balance between procoagulant and anticoagulant as well as profibrinolytic and antifibrinolytic protein activities. Modern coagulation management of bleeding patients implies ongoing monitoring of coagulation status with subsequent individual and goal-directed treatment. The key to success in terms of patient outcomes is to keep the above-mentioned four elements of the coagulation system in optimal equilibrium so that bleeding is adequately controlled without thromboembolic adverse events. The coagulation system is a complex network of interacting proteins and cells with extensive sensitivity, amplification, and control pathways. There is no simple answer to coagulation management; instead, optimal coagulation intervention and management needs to be defined for each patient. Advanced coagulation monitoring will employ a combination of routine laboratory tests using single factor measurements and whole blood as well as point-of-care coagulation testing—always keeping in mind patient history and clinical findings. Whole-blood coagulation tests like Thrombelastography (Haemonetics Corporation, Braintree, MA) or rotation Thromboelastometry (Tem International GmbH, Munich, Germany) may overcome some of the limitations of routine laboratory coagulation tests and are increasingly being used in massive bleeding. With minimal time delays, they provide valuable information on overall kinetics of clot formation, clot strength, platelet function, and overt fibrinolysis in whole blood. However, these tests are still in vitro assays; they do not reflect in vivo contributions of local tissue and the endothelium, tissue factor–bearing cells, and blood flow to the naturally occurring coagulation process. Therefore, any coagulation test requires skilled interpretation and clinical correlation to evaluate its significance for bleeding or thrombosis. Patients with massive hemorrhage become coagulopathic due to several mechanisms. Trauma and shock directly activate the thrombomodulin-protein C pathway, resulting in the acute coagulopathy of trauma and shock. Thereby, key players of the propagation phase of coagulation, the tenase (VIIIa-IXa) and prothrombinase (Xa-Va) complex, are getting degraded and inactivated by activated protein C. Furthermore, plasminogen activator inhibitor 1, the principal inhibitor of tissue plasminogen activator and urokinase, is inhibited through activated protein C, resulting in increased fibrinolysis. The developing coagulopathy then worsens through the better known pathogenetic factors: consumption and dilution of coagulation factors, hypothermia, and acidosis. Fibrinogen is the substrate of coagulation and is usually the first coagulation factor to become critically low in massive bleeding. According to Hiippala, fibrinogen levels fall below 1 g/l after a loss of 150% of the calculated blood volume. Factors II, V, and VII as well as platelet levels become critical later, after a blood volume loss of more than 200%. However, these figures are very general and do not help greatly in individual cases. In addition, the arbitrary definition of the critical level determines when the corresponding level will be reached (i.e., after what blood volume loss). If patients present with clinical and objective signs of coagulopathic bleeding, treatment with allogeneic blood products (e.g., fresh frozen plasma, cryoprecipitate, platelet concentrates), factor concentrates, pharmacological interventions, or a combination thereof has to be initiated. Evidence-based recommendations, such as the recent one from the multidisciplinary Task Force for Advanced bleeding Care in Trauma, are very helpful for optimal patient care. One Accepted for publication June 29, 2010. Dr. Spahn has received honoraria or travel support for consulting or lecturing on this topic from CSL Behring GmbH (Hattersheim am Main, Germany, and Bern, Switzerland) and Tem International, formerly Pentapharm GmbH (Munich, Germany). Dr. Ganter has received honoraria or travel support for consulting or lecturing on this topic from CSL Behring GmbH (Hattersheim am Main, Germany, and Bern, Switzerland). This Editorial View accompanies the following article: Bolliger D, Görlinger K, Tanaka KA: Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. ANESTHESIOLOGY 2010; 113:1205–19.