Antithrombin is not protective against renal ischaemia-reperfusion injury

Abstract

Letters to the Editor Dear Sirs, Antithrombin (AT) is a natural anticoagulant, belonging to the serine proteaseinhibitor (serpin) family, that inhibits several coagulation serine proteases, mainly factor Xa and thrombin. At high concentrations, 2.5-to 10-fold plasma levels, AT also exerts antiinflammatory properties when bound to heparan sulfate proteoglycans (HSPGs) (1, 2), making it a good candidate for supportive therapy in clinical settings of inflammation and coagulation activation. Indeed, AT has already been evaluated in vivo mainly in two situations, ischaemia-reperfusion injury (IRI) (3-5) and severe sepsis (6, 7). However, in a large-scale clinical trial, AT obtained no survival benefit for patients with severe sepsis (8). In 2003, Mizutani et al. reported an AT protective effect in a murine model of renal IRI. However, withdrawal in 2013 of that publication might raise doubts about AT cytoprotection in that context

An Inhibitory Single-Domain Antibody against Protein Z-Dependent Protease Inhibitor Promotes Thrombin Generation in Severe Hemophilia A and FXI Deficiency

“…It should be noted that ZPI-sdAb2 is the first molecule found to inhibit ZPI's anti-FXa and anti-FXIa activities simultaneously. This sdAb appears to be selective for ZPI because it does not bind AT or α1-AT -two members of the serpin superfamily that are structurally homologous with ZPI 32 and are abundant in plasma 33,34 . Furthermore, ZPI-sdAb2 does not bind to PAI-1, a serpin involved in the regulation of fibrinolysis and the inhibition of which might trigger an unwanted profibrinolytic effect.…”