Judith Martini1, Pedro Cabrales, Dietmar Fries, Marcos Intaglietta, Amy G Tsai. 1. 1Department of Anesthesia and Intensive Care Medicine, Medical University InnsbruckInnsbruckAustria. 2Department of Bioengineering, University of California, San Diego (UCSD)La JollaCA. 3Clinical Department of General and Surgical Intensive Care Medicine, Medical University InnsbruckInnsbruckAustria.
Abstract
OBJECTIVES: Dilutional coagulopathy after resuscitation with crystalloids/colloids clinically often appears as diffuse microvascular bleeding. Administration of fibrinogen reduces bleeding and increases maximum clot firmness, measured by thromboelastometry. Study objective was to implement a model where microvascular bleeding can be directly assessed by visualizing clot formation in microvessels, and correlations can be made to thromboelastometry. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Syrian Golden hamsters. INTERVENTIONS: Microvessels of Syrian Golden hamsters fitted with a dorsal window chamber were studied using videomicroscopy. After 50% hemorrhage followed by 1 hour of hypovolemia resuscitation with 35% of blood volume using a high-molecular-weight hydroxyethyl starch solution (Hextend, Hospira, MW 670 kD) occurred. Animals were then treated with 250 mg/kg fibrinogen IV (Laboratoire français du Fractionnement et des Biotechnologies, Paris, France) or an equal volume of saline before venular vessel wall injuries was made by directed laser irradiation, and the ability of microthrombus formation was assessed. MEASUREMENTS AND MAIN RESULTS: Thromboelastometric measurements of maximum clot firmness were performed at the beginning and at the end of the experiment. Resuscitation with hydroxyethyl starch and sham treatment significantly decreased FIBTEM maximum clot firmness from 32 ± 9 mm at baseline versus 13 ± 5 mm after sham treatment (p < 0.001). Infusion of fibrinogen concentrate significantly increased maximum clot firmness, restoring baseline levels (baseline 32 ± 9 mm; after fibrinogen administration 29 ± 2 mm). In vivo microthrombus formation in laser-injured vessels significantly increased in fibrinogen-treated animals compared with sham (77% vs 18%). CONCLUSIONS: Fibrinogen treatment leads to increased clot firmness in dilutional coagulopathy as measured with thromboelastometry. At the microvascular level, this increased clot strength corresponds to an increased prevalence of thrombus formation in vessels injured by focused laser irradiation.
OBJECTIVES:Dilutional coagulopathy after resuscitation with crystalloids/colloids clinically often appears as diffuse microvascular bleeding. Administration of fibrinogen reduces bleeding and increases maximum clot firmness, measured by thromboelastometry. Study objective was to implement a model where microvascular bleeding can be directly assessed by visualizing clot formation in microvessels, and correlations can be made to thromboelastometry. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Syrian Golden hamsters. INTERVENTIONS: Microvessels of Syrian Golden hamsters fitted with a dorsal window chamber were studied using videomicroscopy. After 50% hemorrhage followed by 1 hour of hypovolemia resuscitation with 35% of blood volume using a high-molecular-weight hydroxyethyl starch solution (Hextend, Hospira, MW 670 kD) occurred. Animals were then treated with 250 mg/kg fibrinogen IV (Laboratoire français du Fractionnement et des Biotechnologies, Paris, France) or an equal volume of saline before venular vessel wall injuries was made by directed laser irradiation, and the ability of microthrombus formation was assessed. MEASUREMENTS AND MAIN RESULTS: Thromboelastometric measurements of maximum clot firmness were performed at the beginning and at the end of the experiment. Resuscitation with hydroxyethyl starch and sham treatment significantly decreased FIBTEM maximum clot firmness from 32 ± 9 mm at baseline versus 13 ± 5 mm after sham treatment (p < 0.001). Infusion of fibrinogen concentrate significantly increased maximum clot firmness, restoring baseline levels (baseline 32 ± 9 mm; after fibrinogen administration 29 ± 2 mm). In vivo microthrombus formation in laser-injured vessels significantly increased in fibrinogen-treated animals compared with sham (77% vs 18%). CONCLUSIONS:Fibrinogen treatment leads to increased clot firmness in dilutional coagulopathy as measured with thromboelastometry. At the microvascular level, this increased clot strength corresponds to an increased prevalence of thrombus formation in vessels injured by focused laser irradiation.