Antithrombin and free tri-iodothyronine in sepsis

Background

Plasmatic activity of antithrombin (AT), a physiological coagulation inhibitor with anti-inflammatory properties, is a marker of severity validated in sepsis. The nonthyroidal illness syndrome, whose first stage is a decrease in free tri-iodothyronine (fT3) plasmatic concentration, is frequently observed in intensive care unit (ICU) patients. Plasmatic levels of fT3 and free thyroxine (fT4) are respectively in correlation with severity and prognosis. The aim of this study is to determine whether a significant correlation exists between T3 and AT in sepsis.

Methods

Eighty-two patients, with 28 of them suffering from sepsis, admitted in the ICU of a general hospital over a 5-month period, were included at random. The exclusion criteria were a history of dysthyroidism or treatment intake that affects thyroid function. The levels of AT, thyroid stimulating hormone (TSH), fT3, fT4, C reactive protein (CRP) and leukocyte count were measured at admission. These investigations concerning blood samples were part of the routine biological balance. APACHE II and SAPS II scores were calculated using data from the first 24 hours of the ICU stay. Patients were followed until ICU discharge or death to determine the survival rate. P < 0.05 and r < 0.05 were considered significant.

Results

A nonlinear significant correlation between AT and T3 was shown in our nonseptic (P = 0.0043, r = 0.393) and septic (P = 0.00220, r = 0.449) population, whereas it was neither with T4 (nonseptic group, P = 0.571; septic group, P = 0,265) or with TSH (nonseptic group, P = 0.993; septic group, P = 0.421). Only in the septic group were AT and fT3 significantly in correlation with gravity, evaluated by APACHE II/SAPS II scores. A significant correlation between fT4 at admission and survival (P = 0.0208) existed only in patients with septic shock. fT3 (1.39 ± 0.56 ng/l vs 2.04 ± 0.54 ng/l, P < 0.0001), as AT (51 ± 22.82% vs 82 ± 23.62%, P < 0.0001), was significantly lower in the septic group. Among other measured parameters, CRP (131 ± 75 mg/l vs 44 ± 53 mg/l, P < 0.0001) and fT4 (9.4 ± 4.15 vs 11.37 ± 3.25 ng/ml, P = 0.0239) were discriminative between the two groups, contrary to the leukocyte count (P = 0.1375). We proposed an explanation of the inter-relation between AT and T3 in sepsis, based upon nuclear properties of T3 on the AT gene and upon effects of AT on the NF-κB path, regulating the peripheral deiodination of T4 to T3.

Conclusions

A significant correlation was underlined in the septic group, at ICU admission, with T3 and AT, whereas it was neither with T4 or with TSH, and with T3, AT and APACHE II/SAPS II gravity scores. A significant correlation between fT4 at admission and survival was found, but only in the septic shock subgroup. The decrease in fT3 is involved in the decrease in AT, reliable to gravity and prognosis. A physiopathological explanation in sepsis could imply NF-κB. Measurement of AT realized in septic patients could be usefully completed by fT3 measurement.