Non-immunogenic staphylokinase in the high-risk pulmonary embolism treatment with subdural hematoma

Aim. To evaluate the safety and efficacy of the non-immunogenic staphylokinase in a patient with a massive high-risk pulmonary embolism (PE) with subdural hematoma.
Material and methods. Non-immunogenic staphylokinase (Fortelyzin®, LLC “SuperGene”, Russia) is an original thrombolytic drug with high fibrin selectivity and minimal risk of bleeding. A clinical case of the non-immunogenic staphylokinase usage at a dose of 15 mg as a single bolus in an elderly patient with massive high-risk PE with subdural hematoma is presented.
Results. Thrombolytic therapy with the non-immunogenic staphylokinase was performed in an 85-years old female with very high mortality risk PE (PESI class V) associated with acute subdural lamellar hematoma, resulting from closed craniocerebral injury. In the first day after thrombolytic therapy, a decrease dyspnea, increase saturation from 74% to 97%, decrease pulmonary artery pressure from 60 to 31 mm Hg, and reduce of right ventricular dysfunction were noted. According to brain CT, on the first day after thrombolysis, an increase in the volume of the subdural hematoma (maximum thickness 8 mm) without dislocation syndrome and without focal neurological deficit was registered. After one week, the patient was discharged. At the follow-up examination after 4 months, regression of the subdural hematoma was noted (the thickness less than 2 mm). The non-immunogenic staphylokinase usage did not lead to major bleeding and hemorrhagic stroke.
Conclusion. The non-immunogenic staphylokinase has shown safety and efficacy in massive PE treatment in an elderly patient with high hemorrhagic risk due to a subdural hematoma.

1. Markov VA, Duplyakov DV, Konstantinov SL, et al. Advanced results of Fortelyzin® use in the FRIDOM1 study and real clinical practice. Russian Journal of Cardiology. 2022;27(8):5178. (In Russ.) DOI:10.15829/1560-4071-2022-5178.

2. Markov VA, Duplyakov DV, Konstantinov SL, et al. Fortelyzin ® versus Metalyse ® in ST-segment elevation myocardial infarction: results of multicenter randomized trial FRIDOM1. Russian Journal of Cardiology. 2018;23(11):110-6. (In Russ.) DOI:10.15829/1560-4071-2018-11-110-116.

3. Gusev EI, Martynov MYu, Nikonov AA, et al.; FRIDA Study Group. Nonimmunogenic recombinant staphylokinase versus alteplase for patients with acute ischaemic stroke 4,5 h after symptom onset in Russia (FRIDA): a randomised, open label, multicentre, parallel-group, non-inferiority trial. Lancet Neurol. 2021;20(9):721-8. DOI:10.1016/S1474-4422(21)00210-6.

4. Gusev EI, Martynov MYu, Shamalov NA, et al. Non-immunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results). Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(7):56-65. (In Russ.) DOI:10.17116/jnevro202212207156.

5. Kirienko AI, Leontyev SG, Tereschenko SH, et al.; FORPE study group. Nonimmunogenic recombinant staphylokinase versus alteplase for patients with massive pulmonary embolism: a randomised open-label, multicenter, parallel-group, non-inferiority trial FORPE. J Thromb Haemost. 2025;23(2):657-67. DOI:10.1016/j.jtha.2024.09.035.

6. Kirienko AI, Leontyev SG, Yarovaya EB, et al. Non-immunogenic staphylokinase — a thrombolytic agent in the treatment of massive pulmonary embolism: results of the FORPE clinical trial. Russian Journal of Cardiology. 2024;29(11):6157. (In Russ.) DOI:10.15829/1560-4071-2024-6157.

7. Leontyev SG, Yarovaya EB, Kutsenko VA, et al. The safety of non-immunogenic recombinant staphylokinase in elderly patients with massive pulmonary embolism: a randomized clinical trial FORPE. Health Sci Rep. 2025;8(5):e70826. DOI:10.1002/hsr2.70826.

8. Boytsov SA, Shakhnovich RM, Tereschenko SN, et al. Features of the Reperfusion Therapy for ST-Segment Elevation Myocardial Infarction According to the Russian Registry of Acute Myocardial Infarction — REGION-IM. Kardiologiia. 2024;64(2):3-17. (In Russ.) DOI:10.18087/cardio.2024.2.n2601.

9. Konstantinov SL, Stryabkova GI, Basarab AI, et al. Non-immunogenic staphylokinase in the treatment of high-risk massive pulmonary embolism in the early postoperative period due to femoral fragment wound. Rational Pharmacotherapy in Cardiology. 2023;19(5):495-501. (In Russ.) DOI:10.20996/1819-6446-2023-2957.

10. Tereshchenko SN, Yarovaya EB, Leontiev SG, et al. Non-immunogenic staphylokinase in patients with massive intermediate-high risk pulmonary embolism: protocol of the FORPE-2 multicenter, double-blind, randomized, placebo-controlled trial. Russian Journal of Cardiology. 2025;30(2):6291. (In Russ.) DOI:10.15829/1560-4071-2025-6291.

11. Zatevakhin II, Chupin AV, Karpenko AA, et al. Intra-arterial thrombolysis with non-immunogenic staphylokinase vs surgery in patients with acute limb ischemia: protocol of a multicenter, open-label, randomized clinical trial FORAT. Angiology and Vascular Surgery. Journal named after Academician A.V. Pokrovsky. 2025;31(2):31-41. (In Russ.) DOI:10.33029/1027-6661-2025-31-2-33-41.