The effects of hypothermia on fibrinogen metabolism and coagulation function in swine

Abstract

Clinical coagulopathy frequently occurs in the presence of hypothermia. The primary purpose of this study was to investigate the effects of hypothermia on clotting protein fibrinogen metabolism and on coagulation function in a swine model. Twelve pigs were randomly allocated into control and hypothermia groups. Hypothermia of 32 degrees C was induced using a blanket with circulating water at 4 degrees C. Fibrinogen synthesis and breakdown were quantified using a 6-hour stable isotope infusion with subsequent gas chromatograph and mass spectrometry analysis. Clotting enzyme thrombin generation kinetics was quantified at baseline and at the end of the infusion. Changes in fibrinogen metabolism and thrombin generation were correlated with coagulation function assessed by thromboelastography (TEG). Hypothermia decreased fibrinogen synthesis from the control value of 2.6 +/- 0.4 to 1.2 +/- 0.2 mg kg(-1) h(-1) (P < .05), with no effect on fibrinogen breakdown. Thrombin generation at the initiation phase was delayed by hypothermia, but there were no changes at the propagation phase. In thromboelastography measurements, the initial clotting time (R time) was prolonged from the baseline value of 3.01 +/- 0.13 to 4.30 +/- 0.24 minutes (P < .05) and clotting rapidity (angle alpha) was decreased from the baseline value of 72.30 +/- 0.90 to 65.34 +/- 1.07 (P < .05). Hypothermia caused no significant changes in clot strength (maximum amplitude) and clot lysis (LY(60)). We concluded that hypothermia caused a potential deficit in fibrinogen availability and a delay in thrombin generation, consequently inhibiting coagulation function. Our data support the current practices of rewarming and prescribing recombinant factor VIIa for hypothermic patients with coagulation defects.