Morphologic, Hemostasiologic and Hemostatic Aspects of Systemic Application of Exogenous Fibrin Monomer in Model of Posttraumatic Bleeding with Underlying Intake of Warfarin
- Authors: Vdovin V.M.1, Shakhmatov I.I.1, Bobrov I.P.1, Orekhov D.A.2, Teryayev V.V.1, Chernus' V.E.1, Momot A.P.1,3
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Affiliations:
- Altay State Medical University
- Altay Regional Cardiology Dispensary
- Altay Branch of the National Medical Research Center for Hematology
- Issue: Vol 31, No 1 (2023)
- Pages: 5-18
- Section: Original study
- URL: https://journals.rcsi.science/pavlovj/article/view/252518
- DOI: https://doi.org/10.17816/PAVLOVJ108736
- ID: 252518
Cite item
Abstract
INTRODUCTION: Earlier, an ability of exogenous fibrin monomer (FM) introduced at low doses to considerably limit posttraumatic blood loss was established by us on an experimental model of warfarin coagulopathy in vivo. However, the morphologic peculiarities of fibrin formation in the wound area were not considered.
AIM: To compare morphologic, hemostasiologic and hemostatic data based on the results of systemic application of exogenous FM to interpret their effects in the model of posttraumatic bleeding with the underlying intake of warfarin.
MATERIALS AND METHODS: In the work, Chinchilla male rabbits were used. A comparative analysis of hemostasiologic effects and of morphologic picture of the surface of the liver in the wound area was conducted after a dosed trauma, with a preliminary systemic introduction of FM (0.25 mg/kg intravenously) or a concentrate of prothrombin complex factors (40 IU/kg intravenously) with the underlying intake of warfarin by animals (0.4–0.5 mg/kg/day per os for 2 weeks).
RESULTS: Introduction of FM in warfarinised animals in the conditions of a dosed experimental liver injury promoted a hemostatic effect comparable with that of a concentrate of prothrombin complex factors. Both hemostatic drugs led to intense fibrin formation that reduced posttraumatic blood loss. The use of FM was associated with increase in the thickness of thrombotic deposits and fibrin fibers in the wound surface in comparison with placebo by 4.0 and 1.6 times, respectively (р < 0.000001). This process actively involved platelets, which led to 1.7 times reduction of their quantity in the lumen of the blood vessels in the wound vicinity (р < 0.0002). No effect of FM on systemic hemostatic reactions in venous blood was found, in contrast to concentrate of prothrombin complex factors.
CONCLUSION: Exogenous FM can produce a local hemostatic effect in the conditions of dosed experimental trauma and coagulopathy induced by warfarin intake. The hemostatic effect was mediated by intense thrombosis on the wound surface with the active recruitment of platelets in the process. The peculiarities of the demonstrated effects of FM may be mediated though the mechanisms of its action that have not yet been identified, which necessitates continuation of the research in this direction.
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##article.viewOnOriginalSite##About the authors
Vyacheslav M. Vdovin
Altay State Medical University
Author for correspondence.
Email: erytrab@gmail.com
ORCID iD: 0000-0002-4606-3627
SPIN-code: 5885-4504
ResearcherId: B-4400-2019
MD, Cand. Sci. (Med.), Associate Professor
Russian Federation, BarnaulIgor' I. Shakhmatov
Altay State Medical University
Email: iish59@yandex.ru
ORCID iD: 0000-0002-0979-8560
SPIN-code: 1574-4980
ResearcherId: B-4629-2019
MD, Dr. Sci. (Med.), Professor
Russian Federation, BarnaulIgor' P. Bobrov
Altay State Medical University
Email: ig.bobrov2010@yandex.ru
ORCID iD: 0000-0001-9097-6733
SPIN-code: 2375-1427
ResearcherId: CAJ-4653-2022
MD, Dr. Sci. (Med.)
Russian Federation, BarnaulDmitriy A. Orekhov
Altay Regional Cardiology Dispensary
Email: orekhoffs@mail.ru
ORCID iD: 0000-0003-0644-6313
SPIN-code: 5301-3553
Russian Federation, Barnaul
Vyacheslav V. Teryayev
Altay State Medical University
Email: teryaevw@yandex.ru
ORCID iD: 0000-0001-5968-3246
SPIN-code: 7117-6858
ResearcherId: CTX-3550-2022
Russian Federation, Barnaul
Vladimir E. Chernus'
Altay State Medical University
Email: chernus97@mail.ru
ORCID iD: 0000-0003-0800-4906
Russian Federation, Barnaul
Andrey P. Momot
Altay State Medical University; Altay Branch of the National Medical Research Center for Hematology
Email: xyzan@yandex.ru
ORCID iD: 0000-0002-8413-5484
SPIN-code: 8464-9030
ResearcherId: M-7923-2015
MD, Dr. Sci. (Med.), Professor
Russian Federation, Barnaul; BarnaulReferences
- Weisel JW, Litvinov RI. Red blood cells: the forgotten player in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis. 2019;17(2):271–82. doi: 10.1111/jth.14360
- Schastlivtsev IV, Lobastov KV, Tsaplin SN, et al. Modern view on hemostasis system: cell theory. Medical Council. 2019;(16):72–7. (In Russ). doi: 10.21518/2079-701X-2019-16-72-77
- Podoplelova NA, Sulimov VB, Tashilova AS, et al. Blood coagulation in the 21st century: existing knowledge, current strategies for treatment and perspective. Pediatric Hematology/Oncology and Immunopathology. 2020;19(1):139–57. (In Russ). doi: 10.24287/1726-1708-2020-19-1-139-157
- Mangin PH, Neeves KB, Lam WA, et al. In vitro flow-based assay: from simple toward more aophisticated models for mimicking hemostasis and thrombosis. Journal of Thrombosis and Haemostasis. 2021;19(2):582–7. doi: 10.1111/jth.15143
- Lugovskoy EV, Makogonenko EM, Komisarenko SV. Molecular mechanisms of formation and degradation of fibrin: Physical, chemical and immunochemical analysis. Kiev: Naukova dumka; 2013. (In Russ).
- Weisel JW, Litvinov RI. Fibrin formation, structure, and properties. In: Parry D.A.D. & Squire J.M., editors. Fibrous Proteins: Structures and Mechanisms. Pt: Subcellular Biochemistry. 2017;82:405–56. doi: 10.1007/978-3-319-49674-0_13
- Momot AP, Vdovin VM, Orekhov DA, 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. Pathogenesis. 2020;18(4):32–42. (In Russ). doi: 10.25557/2310-0435.2020.04.32-42
- Vdovin VM, Momot AP, Krasyukova VO, et al. Systemic Hemostatic and Hemostasiological Effects of Fibrin Monomer in Direct Thrombin Inhibition in Experiment. Russian Journal of Physiology. 2019;105(2):207–15. (In Russ). doi: 10.1134/S0869813919020109
- Vdovin VM, Momot AP, Shakhmatov II, 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. Kazan Medical Journal. 2021;102(5):642–53. (In Russ). doi: 10.17816/KMJ2021-642
- Park K–J, Kwon E–H, Kim H–J, et al. Evaluation of the Diagnostic Performance of Fibrin Monomer in Disseminated Intravascular Coagulation. The Korean Journal of Laboratory Medicine. 2011;31(3):143–7. doi: 10.3343/kjlm.2011.31.3.143
- Vdovin VM, Momot AP, Orehov DA, et al. Systemic hemostatic and hemostasiological effects of fibrin monomer in low dose under warfarin action in experiment. Tromboz, Gemostaz i Reologiya. 2019;79(3):16–23. (In Russ). doi: 10.25555/THR.2019.3.0885
- Mironov AN, editor. Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv. Pt. 1. Moscow: Grif i K; 2012. (In Russ).
- Papayan LP, Golovina OG, Chechetkin AV, et al. Algoritm diagnostiki gemostaza i monitoring antitromboticheskoy terapii. Saint-Petersburg; 2016. (In Russ).
- Zerbino DD, Lukasevich LL. Disseminirovannoye vnutrisosudistoye svertyvaniye krovi: Fakty i kontseptsii. Moscow: Meditsina; 1989. (In Russ).
- Vdovin VM, Momot AP, Orekhov DA, et al. Influence of Exogenous Fibrin Monomer on Hemostatic Potential and Formation of Fibrin in the Area of Dosed Liver Injury in Experiment. Russian Journal of Physiology. 2020;106(9):1132–1143. (In Russ). doi: 10.31857/S0869813920070092
- Collet JP, Park D, Lesty C, et al. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed: dynamic and structural approaches by confocal microscopy. Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20(5):1354–61. doi: 10.1161/01.atv.20.5.1354
- Wolberg AS. Thrombin generation and fibrin clot structure. Blood Reviews. 2007;21(3):131–42. doi: 10.1016/j.blre.2006.11.001
- Reimers RC, Sutera SP, Joist JH. Potentiation by red blood cells of shear-induced platelet aggregation: relative importance of chemical and physical mechanisms. Blood. 1984;64(6):1200–06.
- Goel MS, Diamond SL. Adhesion of normal erythrocytes at depressed venous shear rates to activated neutrophils, activated platelets, and fibrin polymerized from plasma. Blood. 2002;100(10):3797–803. doi: 10.1182/blood-2002-03-0712
- Whelihan MF, Lim MY, Mooberry MJ, et al. Thrombin generation and cell-dependent hypercoagulability in sickle cell disease. Journal of Thrombosis and Haemostasis. 2016;14(10):1941–52. doi: 10.1111/jth.13416