HSGAG binding enhances AAS19 inhibition of thrombin and factor IXa, but inhibits its activity against factors Xa and XIIa. HSGAG binding improved rAAS19 inhibitory activity 2.7–4.3 folds as determined by stoichiometry of inhibition analysis. rAAS19 in complex with HSGAGs dramatically delays plasma clotting time much more than rAAS19 or HSGAGs alone.