orrhagic coagulopathy is involved in the morbidity and mortality of trauma patients. Nonetheless, many aspects of the mechanisms underlying this disorder are poorly understood. We have therefore investigated changes in fibrinogen metabolism and coagulation function after a moderate hemorrhagic shock, using a new stable isotope approach. Twelve pigs were randomly divided into the control (C) and hemorrhage (H) groups. Hemorrhage was induced by bleeding 35% total blood volume over a 30-min period. A primed constant infusion of [1-13 C]phenylalanine (Phe), d5-phenylalanine, and ␣-[1-13 C]-ketoisocaproate (KIC) was given to quantify fibrinogen synthesis and breakdown, together with measurements of circulating liver enzyme activities and coagulation function. Mean arterial pressure was decreased by hemorrhage from 89 Ϯ 4 mmHg in C to 47 Ϯ 4 mmHg in H (P Ͻ 0.05), followed by a rebound to 68 Ϯ 5 mmHg afterward. Fibrinogen fractional synthesis rate increased from 2.7 Ϯ 0.2%/h in C to 4.2 Ϯ 0.4%/h in H by Phe (P Ͻ 0.05) and from 3.1 Ϯ 0.4%/h in C to 4.4 Ϯ 0.5%/h in H by KIC (P Ͻ 0.05). Fibrinogen fractional breakdown rate increased from 3.6 Ϯ 1.0%/h in C to 12.9 Ϯ 1.8%/h in H (P Ͻ 0.05). The absolute breakdown rate accelerated from 3.0 Ϯ 0.4 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 in C to 5.4 Ϯ 0.6 mg ⅐ kg Ϫ1 ⅐ h Ϫ1 in H (P Ͻ 0.05), but the absolute synthesis rate remained unchanged. These metabolic changes were accompanied by a reduction in blood clotting time to 92.7 Ϯ 1.6% of the baseline value by hemorrhage (P Ͻ 0.05). No changes were found in liver enzyme activities. We conclude that the observed changes in coagulation after hemorrhagic shock are mechanistically related to the acute acceleration of fibrinogen degradation. stable isotopes; fibrinogen metabolism; hemorrhage; coagulation HEMORRHAGIC COAGULOPATHY (without neurological injury) constitutes 40% of injury-related death in civilian hospitals and on the battlefield (1,3,15,18). Hemorrhagic coagulopathy includes an initial hypercoagulable state that may result in consumptive depletion of fibrinogen and progress to disseminated intravascular coagulation (DIC; see Refs. 2,7,8,11,12,18,22). DIC results in a paradoxical situation in which patients are hypocoagulable in terms of hemostasis and therefore cannot stop bleeding, and yet inappropriately deposit fibrin in the microvasculature, contributing to later organ failure in patients that survive the initial hemorrhagic insults. It appears that the availability and metabolism of fibrinogen may play a role in the development of the pathophysiological process. However, the relation between changes in fibrinogen metabolism to the development of clotting defects is poorly understood. The complexity of the clinical settings, such as tissue injury, blood loss, blood transfusion, and resuscitation, makes it difficult to clarify the mechanism contributing to the development of clotting disorders. Therefore, we have used an animal model that allowed us to define changes in fibrinogen metabolism under hemorrhage shock.The essence of the coagulat...