In the conventional view, adequate levels of intravascular FIX (red) are necessary and sufficient for normal hemostasis. Cooley et al propose that two-thirds of total body FIX is in an extravascular compartment bound to collagen IV (white), where it is hemostatically active. Consequently, pharmacokinetic parameters (eg, plasma half-life), which are a mainstay in conventional therapy, are not predictive in their model. Professional illustration by Patrick Lane, ScEYEnce Studios.