The appended tail region of heparin cofactor II and additional reactive centre loop mutations combine to increase the reactivity and specificity of α1-proteinase inhibitor M358R for thrombin

Natural inhibitors of coagulation or inflammation such as the serpins antithrombin (AT), heparin cofactor II (HCII), and alpha(1)-proteinase inhibitor (alpha(1)-PI) can be overwhelmed in thrombosis and/or sepsis. The reactive centre (P1-P1') variant alpha(1)-PI M358R inhibits not only procoagulant thrombin but also anticoagulant activated protein C (APC). We previously described HAPI M358R, comprising a fusion of HCII residues 1-75 to the …