Provided herein are antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human activated Protein C (aPC) with minimal binding to its zymogen Protein C (PC). Moreover, these aPC binding proteins could potentially block the anti-coagulant activity of aPC to induce coagulation. Therapeutic uses of these binders are described herein as are methods of panning and screening specific antibodies.