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To determine if plasma iron concentration is different between horses with and without systemic inflammation (SI) and to assess the accuracy for the detection of SI by assaying plasma iron and fibrinogen concentrations, individually or combined. To assess the prognostic value of plasma iron concentration and to describe the progression of plasma iron and fibrinogen concentrations during hospital follow-up, and its relation to SI and survival.Prospective observational study evaluating plasma iron and fibrinogen.University veterinary teaching hospital.Equine patients greater than 30 days of age.None.Plasma iron and fibrinogen concentration was prospectively determined in hospitalized horses. Horses were classified into 2 groups: SI and non-SI. Horses were also classified according to clinical outcome. A group of control healthy horses was also included. A total of 135 horses were included in the study. Plasma iron concentration was significantly lower and fibrinogen concentration was higher in the SI group. Nonsurvivors had a mean plasma fibrinogen concentration significantly higher than survivors. The combination of plasma iron and fibrinogen has a high degree of specificity, sensitivity, and accuracy for the detection of SI in horses. Follow-up measurements were obtained in 48 horses. Surviving horses normalized plasma iron concentration during follow-up examination whereas nonsurviving horses had persistently low plasma iron concentrations.Plasma iron concentration alone is an accurate marker of SI in hospitalized horses. Alteration of both plasma iron and fibrinogen concentrations improves the specificity and positive predictive value for diagnosis of SI. Alteration of either one of both increases sensitivity and negative predictive value. Surviving horses normalized plasma iron concentrations during follow-up period. The combination of plasma iron and fibrinogen concentrations may help in the detection of SI. Follow-up of plasma iron concentrations may provide useful prognostic information.