Correcting the hemophilic imbalance

Abstract

In this issue of Blood, Polderdijk et al design and evaluate a therapeutic inhibitor of activated protein C.1 They have produced a recombinant variant of α1-antitrypsin (α1AT) incorporating 3 residue changes within the P2-P1′ sequence of its reactive loop. This variant (termed KRK α1AT) exhibits high specificity and inhibitory efficiency toward activated protein C. It is able to restore thrombin generation in normal and in hemophilia plasmas, when these are supplemented with soluble thrombomodulin. It is able to restore hemostasis in challenged hemophilia mice. KRK α1AT is therefore a potentially valuable future therapeutic agent for the human hemophilias.