A novel mechanism of action for hemophilia treatment has emerged with the introduction of Marstacimab. This new human monoclonal IgG1 antibody enhances thrombin production by amplifying the extrinsic pathway of the coagulation cascade, effectively circumventing deficiencies in the intrinsic pathway. Hemophilia, a rare congenital bleeding disorder, is characterized by a deficiency in coagulation factors; Hemophilia A involves a lack of factor VIII, while Hemophilia B is due to a deficiency of factor IX. Traditionally, patients have managed their condition through intravenous infusions of either plasma-derived or recombinant factors to reduce bleeding episodes. Marstacimab operates on a different principle by targeting the Kunitz domain 2 (K2) of the Tissue Factor Pathway Inhibitor (TFPI). TFPI plays a crucial role in inhibiting the extrinsic coagulation cascade by blocking the active site of factor Xa. By neutralizing the inhibitory effects of TFPI on coagulation, Marstacimab increases the availability of free factor Xa, thereby enhancing the extrinsic pathway and compensating for the absent factor VIII or IX in hemophilia patients. This results in improved thrombin formation and overall hemostasis. Currently, Marstacimab (marketed as Hympavzi®) has received approval for routine prophylaxis against bleeding episodes in patients aged twelve and older who have severe Hemophilia A or B, characterized by factor levels below 1% and a body weight of at least 35 kg, provided they do not have inhibitors. Before initiating treatment with Marstacimab, patients must discontinue any ongoing therapy with coagulation factor concentrates. The antibody is administered via subcutaneous injection once a week, starting with a 300 mg dose. Following this initial dose, patients are given 150 mg weekly. For individuals weighing 50 kg or more, an increase to 300 mg weekly may be considered if bleeding control is insufficient. This dosage should not be exceeded. Patients are advised to remove the medication from refrigeration 15 to 30 minutes prior to injection. The recommended sites for administration are the abdomen and thigh, utilizing two different injection sites for the initial 300 mg dose, which consists of two 150 mg injections. After proper training, patients can self-administer the injections. If a dose is missed, it should be taken as soon as possible, up until the day of the next scheduled dose. After that, the normal weekly regimen should resume. However, if over 13 days have passed since the last dose, treatment should restart with a single initial dose of 300 mg, followed by the standard 150 mg weekly schedule. For patients undergoing major surgical procedures, it is recommended to pause Marstacimab treatment six to twelve days before the operation and switch to a coagulation factor concentrate therapy in the interim.