Emicizumab and Recombinant FVIIa for Safe Surgical Removal of a Massive Pseudotumor in Severe Hemophilia A with Inhibitor

Case Study A 45-year-old man was referred to our Haemophilia Treatment Centre (Sydney, New South Wales, Australia) with a chronic large pseudotumor which developed after an injury to his knee. This is on a background of severe hemophilia A complicated by an inhibitor to FVIII. He is from the Pacific Islands, and his only treatment for bleeds to date had been with on-demand cryoprecipitate and intermittent low-dose recombinant FVIII when available through medical aid programs. He typically experienced three to four bleeds a month with target joints including the right knee and right elbow. At baseline, his aPTT was >150 seconds (normal range: 25–37 seconds), his factor VIII level was <1% on both single-stage and chromogenic assays (normal range: 50–200%) and his inhibitor was 3.1 BU/mL (normal range <0.5 BU/mL). The right knee mass was measured as 20-cm wide, 15-cm high, and 16-cm deep ([ Fig. 1A ]). It had been increasing in size with ongoing pain limiting his function and quality of life. He was house-bound due to limited range of motion with an exercise tolerance of 10 to 20 m, and was deemed at risk of spontaneous fracture due to osseous remodeling of the femoral shaft. Fig. 1 ( A ) Clinical photograph demonstrating pseudotumor appearance. ( B ) Preoperative MRI. ( C ) En bloc removal of pseudotumor. ( D ) Histopathological dissection. MRI, magnetic resonance imaging. On examination, he weighed 45 kg, and there was muscle wasting present in all limbs. There was marked quadriceps muscle wasting bilaterally with the evident pseudotumor dislocating his patella, and he was unable to fully flex or extend the knee joint. There were overlying skin changes with hemosiderin deposits, and he was neurovascularly intact. Preoperative imaging with both MRI and PET scan were consistent with the diagnosis of pseudotumor, demonstrating “variegated T1 and T2 signal with multiple areas of T2 hypointensity consistent with the presence of hemosiderin… with extensive intramuscular as well as subcutaneous components… consistent with a large pseudotumor” ([ Fig. 1B ]). His case was discussed at a combined rheumatology/orthopedic meeting with a consensus recommendation for operative intervention. This was to be done with emicizumab prophylaxis and bypass therapy with recombinant FVIIa (rFVIIa). He was commenced on tranexamic acid 1 g four times a day, which continued throughout the operative period. The rationale for using the combination of emicizumab and rFVIIa, even though the patient had a low-titer inhibitor (3.1 BU), was first to avoid an anamnestic response that would further complicate hemostatic management. Second, there is the potential benefit of the synergistic hemostatic effects of emicizumab and rFVIIa, resulting in lower packed red blood cells and rFVIIa infusion requirements.[ 1 ] From 12 days prior to surgery, he commenced a rapid loading protocol for emicizumab, 6 mg/kg on D1, 3 mg/kg on D2, 1.5 mg/kg on D8, and then 1.5 mg/kg weekly from D15 for 8 weeks, giving a total duration of 10 weeks of therapy. An emicizumab level performed on D2 was 12 μg/mL, and 21 μg/mL on D7. He underwent an angiogram and IR embolization of the blood vessels to the pseudotumor 3 days prior to surgery. This was performed under rFVIIa (90 μg/kg q2h × 3 doses = 12 mg in total) cover. This was done irrespective of the emicizumab level as emicizumab alone would not have been sufficient for IR embolization in a patient with an inhibitor. The angiogram confirmed a moderately hypervascular right distal femoral/knee pseudotumor fed by several genicular arteries with intra-lesional vascular lakes; embolization was performed to the dominant vessels with 100 to 300 μm microspheres and 350 to 500 μm PVA particles with end-point of pruning while preserving flow in the main genicular branches. There were no bleeding or thrombotic complications with use of rFVIIa. On the day of surgery, he commenced rFVIIa 90 μg/kg q2h and the mass was successfully removed en bloc ([ Fig. 1C ]), which showed the appearance of a hematoma macroscopically ([ Fig. 1D ]). Histopathology confirmed the diagnosis of hemophilic pseudotumor characterized by organizing hematoma and fibroadipose tissue with hemosiderin deposition, foamy histiocytes, cholesterol clefts, dystrophic calcification, and patchy chronic inflammation. There was no evidence of malignancy. He continued a weaning course of rFVIIa completed by D9 postsurgery. There was no thromboembolism or thrombotic microangiopathy, and he required a single transfusion of packed red cells for intraoperative blood loss. He had an uncomplicated postoperative course with no breakthrough bleeds and is now mobilizing independently. The total perioperative dose of rFVIIa required was 236 mg and the cumulative dose of emicizumab used prophylactically during surgery and in the 3 months postoperatively was 945 mg. At 1 year post-surgery, the pseudotumor had not recurred even though the patient has not had emicizumab prophylaxis. However, longer term outcomes are not available. Publication History Received: 03 March 2026 Accepted after revision: 25 July 2026 Article published online: 04 August 2026 © 2026. Thieme. All rights reserved. Thieme Medical Publishers, Inc. 333 Seventh Avenue, 18th Floor, New York, NY 10001, USA