Fibrinogen concentrate and allogeneic blood transfusion in high-risk surgery.

7 January 2013 P HYSICIANS have long sought alternatives to transfusion of allogeneic blood products for managing patients with or at risk of excessive blood loss. The complications of allogeneic blood, including transfusion reactions, transmission of infectious agents, and acute lung injury, are well known; however, the repletion of the cellular and soluble components of blood becomes necessary when the losses (and attendant volume resuscitation) themselves contribute to ineffective hemostasis. The appropriate trigger for the administration of platelets and plasma coagulation factors is controversial, as is the proper sequence for their administration and methodology for preparing factor replacement products. In this issue of ANESTHESIOLOGY, Rahe-Meyer et al.1 report data from a randomized controlled trial (RCT) demonstrating potential of fibrinogen concentrate as a first-line therapy to reduce transfusion in patients undergoing high-risk surgical procedures. Fibrinogen (factor I) is a large glycoprotein (340 kDa) that circulates as a soluble plasma component. Its plasma concentration (approximately 150–400 mg/dl) is exceeded only by albumin and immunoglobulins, and as an acute phase protein, its concentration increases after surgery and trauma, often exceeding 600 mg/dl. Fibrinogen plays two critical roles in hemostasis. First, in its soluble form, it serves as the ligand for activated GPIIb-IIIa receptors on platelets, constituting the cross bridges among platelets required for aggregation and primary hemostatic plug formation. Second, when cleaved by thrombin (factor IIa), fibrinogen is converted into fibrin, which polymerizes into an insoluble form that stabilizes the hemostatic plug and provides a firm meshwork for clot propagation. The appropriate plasma concentration for fibrinogen in the bleeding patient is not known; however, both recent laboratory and clinical studies suggest that higher is better.2 Indeed, before 2008, transfusion guidelines from American and European societies recommended a plasma fibrinogen target of approximately 100 mg/dl, whereas more recent European guidelines target levels of 150–200 mg/ dl2. Recommendations are based primarily on expert opinion and laboratory studies with few RCTs to guide treatment. The saturation of platelet fibrinogen receptors and normal clot initiation in vitro, as assessed by prothrombin and activated partial thromboplastin times, are known to occur at fibrinogen concentrations at or below the 100 mg/dl threshold.3,4 However, clot formation in vivo is far more complex than these few in vitro tests might suggest. Recent laboratory studies demonstrate a direct relationship between fibrinogen concentration and viscoelastic measures of clot strength that extends through the entire physiologic range for fibrinogen up to 1,000 mg/dl.4–6 These in vitro studies are corroborated by multiple observational studies and nonrandomized trials, which suggest improved hemostasis when fibrinogen concentrations exceed 200 mg/dl.7,8 Fibrinogen Concentrate and Allogeneic Blood Transfusion in High-risk Surgery