Antithrombin sepsis

There are various inhibitors within the coagulation system that counterregulate activation of the coagulation cascade. Among them, antithrombin III (AT-III) and protein C (PC) are the most important (SI). AT-III binds in the presence of heparin the activated factors F-IXa, F-Xa, and F-IIa (thrombin). PC is activated by a complex formed between thrombin and thrombomodulin, a surface protein of endothelial cells. Once activated, PC in the presence of protein S (PS) specifically degrades activated factors F-Va and F-VIIIa. PC decreases in the course of sepsis in relation to the severity of the condition (L15). Experimental studies have... 

With respect to both the coagulation and fibrinolytic cascade systems, in 28 patients who developed septic shock a relation was found between lowered plasma levels of F-XII and antithrombin III and elevated levels of PAI-1 and thrombin-antithrombin III complexes at the diagnosis of sepsis and the severity of disease, expressed according to the APACHE II scoring system (L7). Nevertheless, administration of inhibitors of coagulation or enhancement of fibrinolysis did not improve the outcome in patients with sepsis (B35). 

Antithrombin and activated protein C concentrates are available for the appropriate indications that include thrombosis in the setting of antithrombin deficiency and sepsis respectively. 

Plasma contains protease inhibitors that rapidly inactivate the coagulation proteins as they escape from the site of vessel injury. The most important proteins of this system are -anti protease, 2-macroglobulin, -antiplasmin, and antithrombin. If this system is overwhelmed, generalized intravascular clotting may occur. This process is called disseminated intravascular coagulation (DIC) and may follow massive tissue injury, cell lysis in malignant neoplastic disease, obstetric emergencies such as abruptio placentae, or bacterial sepsis. 

High doses of antithrombin III, given to patients with severe sepsis, increased the risk of hemorrhage, particularly when it was given concomitantly with heparin, while there was no treatment benefit (4). 

Chalupa P, Atherstone A, Penzes I, Kubler A, Knaub S, Keinecke HO, Heinrichs H, Schindel F, Juers M, Bone RC, Opal SM KyberSept Trial Study Group. Caring for the critically ill patient. High-dose antithrombin III in severe sepsis a randomized controlled trial. JAMA... 

Although there is much anecdotal evidence that TPN (as opposed to no nutrition) may be beneficial in hospitalized horses, this has not been proven (Lopes White 2002). The administration of TPN increases the risk of sepsis and thrombophlebitis in hospitalized human patients (loannides-Demos et al 1995). This may result, at least in part, from decreased intracellular killing by neutrophils (Okada et al 2000) and increased plasma thrombin-antithrombin III concentrations, which result in increased plasma coagulability (van der Poll et al 1998). 

When the subgroup of patients treated with antithrombin without heparin was compared with placebo patients that did not receive heparin, the 90-day mortality rate was significantly reduced (p <0.05) in the antifhrombin group [31, 35]. Further large trials will be required to demonstrate the therapeutic value of AT supplementation in sepsis as well as for other acquired deficiency indications. 

Observational studies In a retrospective cohort analysis, using an intensive care unit database, of the effect of antithrombin III compared with standard therapy on outcomes and erythrocyte transfusion rates in 545 postoperative surgical patients with severe sepsis, antithrombin III therapy was associated with a significantly higher frequency of erythrocyte transfusion (22 versus 9 units) there was no beneficial effect on mortality [37 ]. 

Moubarak P, Zilker S, Wolf H, Hofner B, Kneib T, KUchenhoff H, Jauch KW, Hartl WH. Activity-guided antithrombin III therapy in severe surgical sepsis efficacy and safety according to a retrospective data analysis. Shock 2008 30(6) 634-41. 

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