Simplified scheme of pro- and anticoagulant reactions in health and hemophilia with targeted PS. Damage to the endothelium activates coagulation resulting in localized generation of thrombin (IIa). PS-dependent anticoagulant mechanisms control the levels of activated factor X (FXa) and FVa thus balancing the coagulation reactions. By targeting PS in hemophilia the inherent procoagulant-anticoagulant imbalance is corrected and the level of thrombin generated is sufficient for hemostasis. APC, activated protein C; TF, tissue factor; TFPIα, tissue factor pathway inhibitor α. Professional illustration by Luk Cox.