Тромбоз, гемостаз и реология

Tromboz, Gemostaz I Reologiya
scientific and practical journal

ISSN 2078–1008 (Print); ISSN 2687-1483 (online)
2025, Original papers
2025

The intravenous administration importance of small doses of exogenous fibrin monomer to minimize post-traumatic blood loss in the experiment: 612.115.1-001.1-005.1-092.4

Original papers
Published 2025-06-03
Vyacheslav М. Vdovin
Altai State Medical University, Ministry of Health of the Russian Federation; 40 Prospekt Lenina, Barnaul 656038, Russia
ФГБОУ ВО «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 656038 Барнаул, проспект Ленина, 40
https://orcid.org/0000-0002-4606-3627 (unauthenticated)
Andrey P. Momot
Altai Branch of the National Medical Research Centre for Hematology, Ministry of Health of the Russian Federation; 1 Lyapidevskogo Str., Barnaul 656045, Russia
Алтайский филиал ФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской Федерации; Россия, 656045 Барнаул, ул. Ляпидевского, 1
https://orcid.org/0000-0002-8413-5484 (unauthenticated)
Igor I. Shakhmatov
Altai State Medical University, Ministry of Health of the Russian Federation; 40 Prospekt Lenina, Barnaul 656038, Russia
ФГБОУ ВО «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 656038 Барнаул, проспект Ленина, 40
https://orcid.org/0000-0002-0979-8560 (unauthenticated)
Mikhail I. Neymark
Altai State Medical University, Ministry of Health of the Russian Federation; 40 Prospekt Lenina, Barnaul 656038, Russia
ФГБОУ ВО «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 656038 Барнаул, проспект Ленина, 40
https://orcid.org/0000-0001-9135-6392 (unauthenticated)
Natalia A. Lycheva
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of the Russian Academy of Sciences (Institute of Poliomyelitis); 8 bldg. 1, Village of Institute of Poliomyelitis, Settlement Moskovskiy, Moscow 108819, Russia; Siberian State Medical University, Ministry of Health of the Russian Federation; 2 Moskovsky Trakt, Tomsk 634050, Russia
ФГАНУ «Федеральный научный центр исследований и разработки иммунобиологических препаратов имени М.П. Чумакова РАН» (Институт полиомиелита); Россия,108819 Москва, поселение Московский, поселок Института полиомиелита, 8, корп. 1; ФГБОУ ВО «Сибирский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 634050 Томск, Московский тракт, 2
https://orcid.org/0000-0002-5842-5728 (unauthenticated)
Dmitry A. Momot
Altai State Medical University, Ministry of Health of the Russian Federation; 40 Prospekt Lenina, Barnaul 656038, Russia
ФГБОУ ВО «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 656038 Барнаул, проспект Ленина, 40
https://orcid.org/0000-0002-7692-5048 (unauthenticated)
Igor P. Bobrov
Altai State Medical University, Ministry of Health of the Russian Federation; 40 Prospekt Lenina, Barnaul 656038, Russia
ФГБОУ ВО «Алтайский государственный медицинский университет» Министерства здравоохранения Российской Федерации; Россия, 656038 Барнаул, проспект Ленина, 40
https://orcid.org/0000-0001-9097-6733 (unauthenticated)

Keywords

fibrin monomer
warfarin
prothrombin complex factor concentrate
parenchymatous post-traumatic bleeding
hemostatic activity
wound histological picture
  Full Text

Abstract

Summary. The present analysis is devoted to new experimental data demonstrating the hemostatic effect of exogenous fibrin monomer (FM) in a model of dosed liver injury in intact animals with its prophylactic administration 1 hour before bleeding. A minimum FM dose (0.25 mg/kg) has been established, it is capable to reduce significantly blood loss, without affecting hemostasis parameters in the systemic bloodstream, in combination with an increase in local fibrin formation at the site of injury. Further, it was found that low-dose FM is able to exhibit hemostatic effects in conditions of pharmacologically induced coagulopathies provoked by the administration of unfractionated heparin, warfarin or double antiplatelet therapy (acetylsalicylic acid in combination with thienopyridine). FM hemostatic activity was comparable to the similar effect of previously known hemostatics — protamine sulfate and recombinant factor VIIa (in the model with heparin),
prothrombin complex factor concentrate (in the model with warfarin) and tranexamic acid (in the model with antiplatelet agents). In all these cases, low-dose FM minimized blood loss without correcting the initially displaced hemostatic balance, stimulating wound fibrin formation with platelet involvement. The redistribution phenomenon of these blood cells between the systemic blood flow, wound vessels, thrombotic
masses and wound blood after the use of FM is described. Based on the obtained results, the authors suggest a vector receptor-mediated attraction of FM and platelets to the site of injury.

For citation: VdovinV.M., Momot A.P., Shakhmatov I.I., Neymark M.I., LychevaN.A., MomotD.A., Bobrov I.P. The intravenous administration importance of small doses of exogenous fibrin monomer to minimize post-traumatic blood loss in the experiment. Tromboz, gemostaz i reologiya. 2025;(2):32–43.
(In Russ.).

References

  1. Zubairov D.M. 100 years of the enzymatic theory of blood clotting. Kazanskij medicinskij zhurnal. 1983;64(3):161–8. (In Russ.).
  2. Barkagan Z.S. Hemostasis. In: Manual of Hematology. Vol. 3. Ed. A.I. Vorobyov. Moscow: N’yudiamed, 2005. 9–147. (In Russ.).
  3. Kuznik B.I. Cellular and molecular mechanisms of regulation of the hemostasis system in norm and pathology: monograph. Chita: Ekspress-izdatel’stvo, 2010. 832 рр. (In Russ.).
  4. Hoffman M., Monroe D.M. Coagulation 2006: a modern view of hemostasis. Hematol Oncol Clin North Am. 2007;21(1):1–11. DOI: 10.1016/j.hoc.2006.11.004.
  5. Ho K.M., Pavey W. Applying the cell-based coagulation model in the management of critical bleeding. Anaesth Intensive Care. 2017;45(2):166–76. DOI: 10.1177/0310057X1704500206.
  6. Wang J., Yu C., Zhuang J. et al. The role of phosphatidylserine on the membrane in immunity and blood coagulation. Biomark Res. 2022;10(1):4. DOI: 10.1186/s40364‑021‑00346‑0.
  7. Panteleev M.A., Dashkevich N.M., Ataullakhanov F.I. Hemostasis and thrombosis beyond biochemistry: roles of geometry, flow and diffusion. Thromb Res. 2015;136(4):699–711. DOI: 10.1016/j.thromres.2015.07.025.
  8. Hoffman M. Remodeling the blood coagulation cascade. J Thromb Thrombolysis. 2003;16(1–2):17–20. DOI: 10.1023/B:THRO.0000014588.95061.28.
  9. Smith S.A. The cell-based model of coagulation. J Vet Emerg Crit Care (San Antonio). 2009;19(1):3–10. DOI: 10.1111/j.1476‑4431.2009 00389.x.
  10. Cap A., Hunt B.J. The pathogenesis of traumatic coagulopathy. Anaesthesia. 2015;70(S1):96‑e34. DOI: 10.1111/anae.12914.
  11. Karkouki K., Wijeysundera D.N., Yau T.M. et al. The independent association of massive blood loss with mortality in cardiac surgery. Transfusion. 2004;44(10):1453–62. DOI: 10.1111/j.1537‑2995.2004.04144.x/
  12. Stuklov N.I., Sushinskaya T.V. Thrombotic and hemorrhagic complications in surgical practice. In: Hemostasis. Theoretical foundations and clinical practice. National guidelines. Eds. O.A. Rukavitsyn, S.V. Ignatiev, A.G. Rumyantsev. Moscow: GEOTAR-Media,2024. 786–806. (In Russ.).
  13. Systemic syndromes in the obstetric and gynecological clinic: a guide for physicians. Ed. A.D. Makatsariya. Moscow: MIA, 2010.888 pp. (In Russ.).
  14. Vinogradova M.A. Hemostasis disorders in obstetrics and gynecology. In: Hemostasis. Theoretical foundations and clinical practice. National guidelines. Eds. O.A. Rukavitsyn, S.V. Ignatiev, A.G. Rumyantsev. Moscow: GEOTAR-Media, 2024. 517–36. (In Russ.).
  15. de Lloyd L., Jenkins P.V., Bell S.F. et al. Acute obstetric coagulopathy during postpartum hemorrhage is caused by hyperfibrinolysis and dysfibrinogenemia: an observational cohort study. J Thromb Haemost. 2023;21(4):862–79. DOI: 10.1016/j.jtha.2022.11.036.
  16. Heckbert S.R., Vedder N.B., Hoffman W. et al. Outcome after hemorrhagic shock in trauma patients. J Trauma. 1998;45(3):545–9. DOI:10.1097/00005373‑199809000‑00022.
  17. Ageno W., Donadini M. Breadth of complications of long-term oral anticoagulant care. Hematology Am Soc Hematol Educ Program. 2018;2018(1):432–8. DOI: 10.1182/asheducation‑2018.1.432.
  18. Peng H.T. Hemostatic agents for prehospital hemorrhage control: a narrative review. Mil Med Res. 2020;7(1):13. DOI: 10.1186/s40779‑020‑00241‑z.
  19. Barkagan Z.S. Medicines used in hematology. In: Federal guidelines for medicines use (formulary system). Issue V. Eds. A.G. Chuchalin, A.I. Vyalkov, Yu. B. Belousov, V.V. Yasnetsov. Moscow: Ekho, 2004.518–837. (In Russ.).
  20. Ehrlich H.J., Henzl M.J., Gomperts E.D. Safety of factor VIII inhibitor bypass activity (FEIBA): 10‑year compilation of thrombotic adverse events. Haemophilia. 2002;8(2):83–90. DOI: 10.1046/j.1365‑2516.2002.00532.x.
  21. Rajpurkar M., Croteau S.E., Boggio L., Cooper D.L. Thrombotic events with recombinant activated factor VII (rFVIIa) in approved indications are rare and associated with older age, cardiovascular disease, and concomitant use of activated prothrombin complex concentrates (aPCC). J Blood Med. 2019;10:335–40. DOI: 10.2147/JBM.S219573.
  22. Momot А.P., Shakhmatov I.I., Lomaev I.S., Terekhov S.S. Method of industrial production of fibrin-monomer from blood plasma. Patent RF No. 2522237 dated of 10.07.2014. Bull. No. 19. 7 pp. (In Russ.). Available at: https://patenton.ru/patent/RU2522237C2. [Accessed: 15.10.2024].
  23. Guidelines for preclinical drug trial. Part 1. Moscow: Grif i K, 2012.944 pp. (In Russ.).
  24. Momot A.P., Vdovin V.M., Shakhmatov I.I. et al. Systemic hemostatic and prothrombotic effects of fibrin monomer in experiment with dosed liver therapy. Sibirskij nauchnyj medicinskij zhurnal. 2019;39(1):6–12. (In Russ.). DOI: 10.15372/SSMJ20190101.
  25. Zubairov D.M. Molecular basis of blood coagulation and thrombus formation. Kazan: Fen, 2000. 364 pp. (In Russ.).
  26. Refaai M.A., Riley P., Mardovina T., Bell P.D. The clinical significance of fibrin monomers. Thromb Haemost. 2018;118(11):1856–66. DOI: 10.1055/s‑0038‑1673684.
  27. Vdovin V.M., Momot A.P, Orekhov D.A. et al. Influence of exogenous fibrin monomer on hemostatic potential and formation of fibrin in the area of dosed liver injury in experiment. Rossijskij fiziologicheskij zhurnal imeni I.M. Sechenova. 2020;106(9):1132–43. (In Russ.). DOI: 10.31857/S0869813920070092.
  28. Momot A.P., Vdovin V.M., Orekhov D.A. et al. Prevention of heparin-associated massive intraoperative bleedings by systemic administration of fibrin monomer in experiment. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2019;63(4):48–55. (In Russ.). DOI: 10.25557/0031‑2991.2019.04.48‑55.
  29. Momot A.P., Vdovin V.M., Orekhov D.A. et al. Effect of an exogenous fibrin-monomer on hemostatic potential and fibrin formation in the area of controlled liver injury on the background of heparin administration in experiment. Patogenez. 2020;18(4):32–42. (In Russ.). DOI: 10.25557/2310‑0435.2020.04.32‑42.
  30. Vdovin V.M., Momot A.P., Orekhov D.A. et al. Systemic hemostatic and hemostasiological effects of fibrin monomer in low dose under warfarin action in experiment. Tromboz, gemostaz i reologiya. 2019;(3):16–23. (In Russ.). DOI: 10.25555/THR.2019.3.0885.
  31. Vdovin V.M., ShakhmatovI. I., BobrovI.P. et al. Morphologic, hemostasiologic and hemostatic aspects of systemic application of exogenous fibrin monomer in model of posttraumatic bleeding withunderlying intake of warfarin. Rossiyskiy mediko-biologicheskiy vestnik imeni akademika I.P. Pavlova. 2023;31(1):5–18. (In Russ.). DOI: 10.17816/PAVLOVJ108736.
  32. Vdovin V.M., Momot A.P., Orekhov D.A. et al. Experimental study of systemic hemostatic effects of fibrin monomer in inhibition of platelet aggregation function. Byulleten’ sibirskoj mediciny. 2020;19(1):36–42. (In Russ.). DOI: 10.20538/1682‑0363‑2020‑1‑36‑42.
  33. Vdovin V.M., Momot A.P., Shakhmatov I.I. et al. Effects of tranexamic acid and exogenous fibrin monomer on the liver injury area and systemic circulation in pharmacological suppression of platelet function in an experiment. Kazanskij medicinskij zhurnal. 2021;102(5):642–53. (In Russ.). DOI: 10.17816/KMJ2021‑642.
  34. Vdovin V.M., Suzopov E.V., Shakhmatov I.I. et al. Morphological determinants for the local hemostatic effect of exogenous fibrin monomer in its systemic administration after injury with inhibition of platelet aggregation in the experiment. Acta biomedical scientifica. 2023;8(4):155–164. (In Russ.). DOI: 10.29413/ABS.2023‑8.4.17.