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Marstacimab is a human monoclonal IgG1 antibody directed against the Kunitz-type domain 2 (KD2) of the tissue factor pathway inhibitor (TFPI). By preventing TFPI-mediated inhibition of the TF/FVIIa/FXa coagulation initiation complex, marstacimab restores thrombin generation after vessel wall injury in patients with congenital deficiency of FVIII (hemophilia A) or FIX (hemophilia B).[1] Marstacimab is administered subcutaneously via a prefilled autoinjector pen with a loading dose of 300 mg and a subsequent flat maintenance dose of 150 mg once weekly. Based on findings from the phase-3 BASIS trial, marstacimab is currently approved for routine prophylaxis of bleeding episodes in patients 12 years of age and older, who weigh at least 35 kg and who have severe hemophilia A or hemophilia B without inhibitors.[2] [3] Concizumab is another humanized monoclonal TFPI antibody of the IgG4 isotype, which also targets KD2, but which is administered on a daily, weight-adjusted basis.[4]

Although marstacimab offers efficacious protection from spontaneous or traumatic bleeds during daily activities, additional on-demand or preventative treatment with clotting factor concentrates (CFCs) may be necessary in case of breakthrough hemorrhages, major trauma, or surgical procedures. As aggressive replacement therapy with CFCs harbors the risk of thromboembolic events under conditions of unleashed TF-driven coagulation,[5] it is advised to discontinue anti-TFPI therapy at least 4 days in case of concizumab, which has an estimated steady-state half-life of approximately 38 hours, and 6–12 days in case of marstacimab, which has an estimated steady-state half-life of 16–18 days, before elective major surgery and to use the lowest effective dosage of CFCs for on-demand treatment in case of uninterrupted anti-TFPI therapy.[3] [6] [7]

Since no routine laboratory tests are currently available to reliably capture the hemostatic protection offered by TFPI antibodies,[8] and since clinical trial data for invasive procedures is scarce,[5] the decision on whether to pause or continue anti-TFPI therapy in surgical patients and whether to use additional antifibrinolytics and/or CFCs is empirical and based on clinical judgment.

A 36-year-old male patient with severe hemophilia B and no history of FIX inhibitor was switched to bleeding prophylaxis with marstacimab in September 2025. His height was 168 cm, and his body weight was 79 kg. The patient had previously been on prophylaxis with an extended half-life (EHL) FIX concentrate at a dosage of 3000 IU (corresponding to approximately 40 IU/kg) once weekly, during which he had not experienced treated breakthrough bleeds over the preceding year. His motivation to switch to marstacimab was primarily based on his discomfort with intravenous injections and his urgent desire to reduce treatment burden. The patient had a history of recurrent urolithiasis and successfully treated chronic hepatitis C, and he suffered from painful hemophilic arthropathy of his knee and ankle joints.

Regarding the patient’s dental history, wisdom tooth 18 in the right upper quadrant had to be removed in June 2024 because of caries profunda and chronic apical periodontitis using local anesthesia and plastic coverage of an oroantral fistula. The patient received 4000 IU of a plasma-derived FIX concentrate (pdFIX) immediately before in-hospital surgery, followed by 2.000 IU of his EHL-FIX concentrate in the outpatient setting on the first and fourth postoperative days. The patient was also advised to take tranexamic acid (TXA) at a dosage of 1 g three times a day for one week after surgery. The clinical course was uneventful with regular wound healing. Wisdom tooth 28 in the left upper quadrant had been removed via osteotomy in October 2021 using a similar perioperative approach.

Because of progressive carious destruction of the second premolar, tooth 25, and second molar, tooth 27, in the left upper quadrant (arrows in [Fig. 1A]), the patient was scheduled to undergo outpatient dental surgery in December 2025. Based on adequate bleeding control during the previous three months of anti-TFPI prophylaxis, it was decided to continue regular marstacimab dosing perioperatively and to administer 1000–2000 IU of pdFIX only in case of excessive bleeding. Prophylactic oral antifibrinolytic therapy with TXA (3 × 1 g/day), however, was commenced on the day before and continued for three days after surgery. The two teeth were extracted using osteotomy, and defects were covered by flap plasties requiring periosteal incision. Nonabsorbable SERALON® sutures (size, 4/0) were removed after 14 days, and wound healing proceeded completely normal ([Fig. 1B]). No excessive bleeding occurred, and no on-demand treatment with pdFIX was necessary. Overall, the patient had not suffered from treated breakthrough bleeds during six months of marstacimab prophylaxis.

Fig. 1 (A) Plain radiographs showing progressive carious destruction of tooth 25 and tooth 27 in the left upper quadrant (arrows) over a 20-month period. (B) Clinical follow-up after dental surgery showing normal wound healing without evidence of excessive bleeding or infection at position 25.

A characteristic feature of high-affinity monoclonal TFPI antibodies is rapid, nonlinear clearance via target-mediated drug disposition (TMDD). In case of marstacimab, key properties of the molecule were modified to allow it to overcome TMDD at low concentrations: marstacimab has lower TFPI binding affinity with a KD of approximately 3.7 nM and exhibits slower clearance rates, resulting in a longer estimated steady-state half-life of 16–18 days.[9] [10] [11] Consequently, marstacimab requires less frequent, once-weekly dosing as compared to concizumab, which is administered daily.[12] The marstacimab summary of product characteristics recommends discontinuing marstacimab prophylaxis 6–12 days before major surgery and initiating CFC replacement therapy according to local standard protocols.[3] This recommendation, however, is based on limited experience obtained from invasive or surgical procedures performed during the phase-3 BASIS and open-label extension trials rather than on pharmacokinetic considerations.[13]

During the BASIS active treatment phase, 14 patients had 17 surgical procedures (15 minor, 2 major), and during the open label extension phase, 7 patients had 8 surgical procedures (6 minor, 2 major). During all 21 minor procedures, marstacimab administration was continued as scheduled, but only four minor procedures were performed without preventative or on-demand CFC replacement therapy: two endodontic procedures, one dental care, and one cooling therapy. In all five reported cases of tooth extractions, standard half-life CFCs were administered at daily dosages of 1000–3500 IU over 1–3 days. All patients with major surgeries received CFC replacement therapy during temporarily discontinued marstacimab treatment.

To the best of our knowledge, we provide the first real-world evidence that outpatient tooth extractions are feasible and safe during continued marstacimab prophylaxis with an additional 5-day course of oral TXA but without preventative or on-demand top-up CFC replacement therapy. Our observation that neither hemorrhagic nor thromboembolic events have occurred in the perioperative setting may inform other patients and healthcare providers in the planning and management of minor surgical procedures, such as tooth extractions, during continued marstacimab prophylaxis.

Received: 11 March 2026

Accepted after revision: 13 April 2026

Article published online:
21 May 2026

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