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 a1-
antitrypsin (a1AT) incorporating 3 residue changes within the P2-P19 sequence of
its reactive loop. This variant (termed KRK a1AT) 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 a1AT is therefore a potentially valuable future therapeutic
agent for the human hemophilias.