Document Detail


Acidosis and coagulopathy: the differential effects on fibrinogen synthesis and breakdown in pigs.
MedLine Citation:
PMID:  17968176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 Blood samples were withdrawn hourly to quantify fibrinogen synthesis and degradation rates using gas chromatograph and mass spectrometry analysis.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.
Authors:
Wenjun Z Martini; John B Holcomb
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Annals of surgery     Volume:  246     ISSN:  0003-4932     ISO Abbreviation:  Ann. Surg.     Publication Date:  2007 Nov 
Date Detail:
Created Date:  2007-10-30     Completed Date:  2007-12-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372354     Medline TA:  Ann Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  831-5     Citation Subset:  AIM; IM    
Affiliation:
US Army Institute of Surgical Research, Fort Sam Houston, Texas, USA. wenjun.martini@amedd.army.mil
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MeSH Terms
Descriptor/Qualifier:
Acidosis / blood*
Animals
Blood Coagulation / physiology*
Blood Coagulation Tests
Disease Models, Animal
Fibrinogen / metabolism*
Hematocrit
Platelet Count
Swine
Time Factors
Chemical
Reg. No./Substance:
9001-32-5/Fibrinogen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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