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Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs

¹United States Army Institute of Surgical Research, Ft. Sam Houston and ²University of Texas Medical Branch, Galveston, Texas; and ³Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts

Submitted 25 March 2005 ; accepted in final form 10 June 2005

Hemorrhagic 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 [1-¹³C]phenylalanine (Phe), d₅-phenylalanine, and -[1-¹³C]-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 ± 4 mmHg in C to 47 ± 4 mmHg in H (P < 0.05), followed by a rebound to 68 ± 5 mmHg afterward. Fibrinogen fractional synthesis rate increased from 2.7 ± 0.2%/h in C to 4.2 ± 0.4%/h in H by Phe (P < 0.05) and from 3.1 ± 0.4%/h in C to 4.4 ± 0.5%/h in H by KIC (P < 0.05). Fibrinogen fractional breakdown rate increased from 3.6 ± 1.0%/h in C to 12.9 ± 1.8%/h in H (P < 0.05). The absolute breakdown rate accelerated from 3.0 ± 0.4 mg·kg^–1·h^–1 in C to 5.4 ± 0.6 mg·kg^–1·h^–1 in H (P < 0.05), but the absolute synthesis rate remained unchanged. These metabolic changes were accompanied by a reduction in blood clotting time to 92.7 ± 1.6% of the baseline value by hemorrhage (P < 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

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