Acidosis and coagulopathy: the differential effects on fibrinogen synthesis and breakdown in pigs.
OBJECTIVE
Uncontrolled bleeding from coagulopathy signals imminent death in severely injured patients. Acidosis is an important predictor of coagulopathy, but the underlying contributing mechanisms are unclear. This study was designed to investigate the effects of acidosis on fibrinogen metabolism and coagulation function in a swine model.


METHODS
Twelve pigs were randomly divided into the control (n = 6) and acid (n = 6) groups. Acidosis of pH 7.1 was induced by infusion of 0.2 M HCl in lactated Ringer solution in the acid group. Afterward, an infusion of stable isotope 1-13C-phenylalanine (6 hours) and d5-phenylalanine (4 hours) was performed. Blood samples were withdrawn hourly to quantify fibrinogen synthesis and degradation rates using gas chromatograph and mass spectrometry analysis. To correlate changes in fibrinogen metabolism, coagulation changes were assessed by prolonged prothrombin time, partial activated thromboplastin time, activated clotting time, and thrombelastograph (TEG).


RESULTS
Acidosis caused decreases in mean arterial pressure, arterial bicarbonate concentration, base excess, fibrinogen concentration, and platelet counts. Acidosis increased fibrinogen degradation rate from the control value of 4.3 +/- 1.0 mg/kg/h to 11.8 +/- 1.4 mg/kg/h (P < 0.05), with no effect on fibrinogen synthesis. Prolonged prothrombin time, partial activated thromboplastin time, activated clotting time were consistently prolonged by acidosis (all P < 0.05). Clotting rapidity (angle alpha in TEG) was decreased from a baseline value of 73.3 +/- 1.1 degree to 63.0 +/- 2.4 degree (P < 0.05). Clot strength (maximum amplitude in TEG) was decreased from a baseline value of 72.2 +/- 1.4 mm to 56.2 +/- 3.1 mm (P < 0.05).


CONCLUSIONS
Acidosis compromised the clotting process and accelerated fibrinogen consumption with no effect on fibrinogen production, resulting in a deficit in fibrinogen availability.
Martini
Wenjun Z
WZ
US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA. wenjun.martini@amedd.army.mil
Holcomb
John B
JB
D000138:Acidosis / Q000097:blood*; D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D001780:Blood Coagulation Tests; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000378:metabolism*; D006400:Hematocrit; D010976:Platelet Count; D013552:Swine; D013997:Time Factors
D005340:Fibrinogen