Thrombin is a multifaceted protein with a wide range of functions. Walter Seegers, a pioneer in thrombin work, referred to it as “the living enzyme of my blood.”1– The central importance of thrombin in biology, physiology, and pathology is clearly shown by studies conducted with genetically homogenous mice made deficient in components of coagulant pathways essential to thrombin generation and its regulation. Transgenic mice deficient in tissue factor,2– factor VII,3– tissue factor pathway inhibitor,4– factor X,5– factor V,6– prothrombin,7– and protein C8 die in utero or shortly after birth. In contrast, in the outbred human population, deficiencies of coagulation components, essential in mice, yield consequences ranging from mild-to-severe pathology. These observations underscore the complexity of managing the outbred human population with respect to interventions for both thrombosis and hemostasis.