Analyse der antithrombotischen Potenz von Antithrombin-III zur Prophylaxe der mikrovaskulären Thrombose

A randomized controlled study (KyberSept-Trial [1]) in patients with severe sepsis showed that anti-thrombin-III significantly reduced lethality in a subgroup of septic patients not receiving concomitant heparin for thrombosis prophylaxis. Therefore, the present study investigated the antithrombotic property of ATIII in an animal study as potential monotherapy in order to omit concomitant heparin therapy. In a light/dye injury model of microvascular thrombosis at the ear of the mouse, we investigated a total of 30 homozygous (SKH1-hr) hairless mice of either sex (10–12 weeks old with a body weight (bw) of 22–40 g) under ip anaesthesia with ketamine/xylazine (90/25 mg/kg bw). Intravital fluorescence microscopy allowed quantitative analysis of the kinetics of thrombus formation in arterioles and venules. Prior to thrombus induction all animals received a single intravenous bolus of hirudin (1 mg/kg bw) or ATIII in dosages of 25, 50, 100 or 250 U/kg bw. Control animals received equivalent volumes of physiologic saline (n=5 animals per group). In saline-treated controls, complete thrombotic occlusion could be induced in 100% of all arterioles (9/9) and venules (40/40) studied. Hirudin prevented thrombotic vessel occlusion in 56% of the arterioles (5/9) and 39% of the venules (9/23). ATIII-250 was found more effective than hirudin, as thrombus formation was banned in all arterioles (13/13) and venules (24/24) (p