Assessment of the effect of exogenous fibrin monomer on post-traumatic bleeding in hypofibrinogenemia caused by administration of snake venom Agkistrodon rhodostoma
V M Vdovin , A P Momot , D A Orekhov , I I Shakhmatov , N A Lycheva , D A Momot
Kazan medical journal ›› 2020, Vol. 101 ›› Issue (5) : 704 -712.
Assessment of the effect of exogenous fibrin monomer on post-traumatic bleeding in hypofibrinogenemia caused by administration of snake venom Agkistrodon rhodostoma
Aim. To assess the effect of fibrin monomer on the rate of blood loss after controlled liver injury in hypofibrinogenemia induced by systemic administration of Malayan pit viper venom (Agkistrodon rhodostoma).
Methods. A placebo-controlled study of the hemostatic effect of fibrin monomer administered intravenously at 0.25 mg/kg, and coagulation parameters in the controlled liver injury with profound hypofibrinogenemia caused by administration of Malayan pit viper venom was conducted in 34 male Chinchilla rabbits. The distribution of the studied parameters was investigated by the Shapiro–Wilk test. Statistical differences between groups were tested by Student’s t-test, Mann–Whitney U test, or Wilcoxon test, as appropriate. Differences in mortality rate were examined using Fisher's exact test.
Results. A model of experimental toxogenic disseminated intravascular coagulation was reproduced, manifested by high mortality of animals (50.0%), severe blood loss (increased blood loss by 1.78 times), hemolysis, a decreased platelet count (by 19.6% of median) and platelet dysfunction, fibrinogen consumption (protein content less than 0.9 g/l), hypocoagulation as well as intensive D-dimer production (increased concentration by 25.0 times of median). A high level of the fibrin derivative demonstrated activation of fibrin formation and fibrinolysis in the bloodstream of the animals. Systemic prophylactic administration of exogenous fibrin monomer after receiving snake venom did not lead to a decrease in post-traumatic bleeding, whereas earlier, during reproduction of disseminated intravascular coagulation caused by streptokinase infusion, such a hemostatic effect of fibrin monomer was shown.
Conclusion. The absence of fibrin monomer effect (at a dose of 0.25 mg/kg) on the severity of blood loss in toxogenic disseminated intravascular coagulation may be associated with more profound disseminated intravascular coagulation and a sharp 25-fold increase in D-dimer levels that can act as a fibrin monomer polymerization inhibitor.
hemostatic system / snake venom / fibrin monomer / liver injury / hemostatic effect / rabbits
| [1] |
Besser M.W., MacDonald S.G. Acquired hypofibrinogenemia: current perspectives. J. Blood Med. 2016; 26 (7): 217–225. DOI: 10.2147/JBM.S90693. |
| [2] |
Weisel J.W., Litvinov R.I. Fibrin formation, structure, and properties. In: Fibrous proteins: structures and mechanisms. D.A.D. Parry, J.M. Squire eds. Subcellular Biochem. 2017; 82: 405–456. DOI: 10.1007/978-3-319-49674-0_13. |
| [3] |
Zubairov D.M. Molekulyarnye osnovy svertyvaniya krovi i tromboobrazovaniya. (Molecular basis of blood clotting and thrombus formation.) Kazan: FEN. 2000; 368 р. (In Russ.) |
| [4] |
Зубаиров Д.М. Молекулярные основы свёртывания крови и тромбообразования. Казань: ФЭН. 2000; 368 с. |
| [5] |
Levy J.H., Goodnough L.T. How I use fibrinogen replacement therapy in acquired bleeding. Blood. 2015; 125 (9): 1387–1393. DOI: 10.1182/blood-2014-08-552000. |
| [6] |
Mosesson M.W. Fibrinogen and fibrin structure and functions. J. Thromb. Haemost. 2005; 3 (8): 1894–1904. DOI: 10.1111/j.1538-7836.2005.01365.x. |
| [7] |
Gaffney P.J. Fibrin degradation products. A review of structures found in vitro and in vivo. Ann. NY Acad. Sci. 2001; 936: 594–610. DOI: 10.1111/j.1749-6632.2001.tb03547.x. |
| [8] |
Gaffney P.J., Lane D.A., Kakkar V.V., Brasher M. Characterisation of a soluble D-dimer-E complex in crosslinked fibrin digests. Thromb. Res. 1975; 7 (1): 89–99. DOI: 10.1016/0049-3848(75)90127-9. |
| [9] |
Marder V.J., Budzynski A.Z., Barlow G.H. Comparison of the physicochemical properties of fragment D derivatives of fibrinogen and fragment D-D of cross-linked fibrin. Biochim. Biophys. Acta. 1976; 427: 1–14. DOI: 10.1016/0005-2795(76)90279-8. |
| [10] |
Hiippala S.T., Myllylä G.J., Vahtera E.M. Hemostatic factors and replacement of major blood loss with plasma-poor red cell concentrates. Anesth. Analg. 1995; 81 (2): 360–365. DOI: 10.1097/00000539-199508000-00026. |
| [11] |
Litvinov R.I. Molecular mechanisms and clinical significance of fibrinolysis. Kazan Medical Journal. 2013; 94 (5): 711–718. (In Russ.) DOI: 10.17816/KMJ1926. |
| [12] |
Литвинов Р.И. Молекулярные механизмы и клиническое значение фибринолиза. Казанский мед. ж. 2013; 94 (5): 711–718. DOI: 10.17816/KMJ1926. |
| [13] |
Lunde J., Stensballe J., Wikkelsø A. et al. Fibrinogen concentrate for bleeding-a systematic review. Acta. Anaesthesiol. Scand. 2014; 58 (9): 1061–1074. DOI: 10.1111/aas.12370. |
| [14] |
Cap A., Hunt B.J. The pathogenesis of traumatic coagulopathy. Anaesthesia. 2015; 70 (1): 96–101. DOI: 10.1111/anae.12914. |
| [15] |
Rourke C., Curry N., Khan S. et al. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J. Thromb. Haemost. 2012; 10 (7): 1342–1351. DOI: 10.1111/j.1538-7836.2012.04752.x. |
| [16] |
Pillai R., Fraser J.F., Ziegenfuss M., Bhaskar B. Influence of circulating levels of fibrinogen and perioperative coagulation parameters on predicting postoperative blood loss in cardiac surgery: a prospective observational study. J. Card. Surg. 2014; 29 (2): 189–195. DOI: 10.1111/jocs.12255. |
| [17] |
Ranucci M., Pistuddi V., Baryshnikova E. et al. Fibrinogen levels after cardiac surgical procedures: association with postoperative bleeding, trigger values, and target values. Ann. Thorac. Surg. 2016; 102 (1): 78–85. DOI: 10.1016/j.athoracsur.2016.01.005. |
| [18] |
Hunault-Berger M., Chevallier P., Delain M. et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: the CAPELAL study. Haematologica. 2008; 93 (10): 1488–1494. DOI: 10.3324/haematol.12948. |
| [19] |
Collis R.E., Collins P.W. Haemostatic management of obstetric hemorrhage. Anaesthesia. 2015; 70 (1): 78–86. DOI: 10.1111/anae.12913. |
| [20] |
Green L., Knight M., Seeney F. et al. The haematological features and transfusion management of women who required massive transfusion for major obstetric hemorrhage in the UK: a population based study. Br. J. Haematol. 2016; 172 (2): 616–624. DOI: 10.1111/bjh.13864. |
| [21] |
Karlsson O., Jeppsson A., Thornemo M. et al. Fibrinogen plasma concentration before delivery is not associated with postpartum haemorrhage: A prospective observational study. Br. J. Anaesth. 2015; 115: 99–104. DOI: 10.1093/bja/aev039. |
| [22] |
Yamada T., Akaishi R., Oda Y. et al. Antenatal fibrinogen concentrations and postpartum haemorrhage. Int. J. Obstet. Anesth. 2014; 23: 365–370. DOI: 10.1016/j.ijoa.2014.06.004. |
| [23] |
Barkagan Z.S., Perfil'ev P.P. Yadovitye zmei i ikh yady. (Venomous snakes and their venom.) Barnaul: Altajskoe knizhnoe izdatel'stvo. 1967; 75 р. (In Russ.) |
| [24] |
Баркаган З.С., Перфильев П.П. Ядовитые змеи и их яды. Барнаул: Алтайское книжное издательство. 1967; 75 с. |
| [25] |
Vdovin V.M., Momot A.P., Orekhov D.A. et al. Posttraumatic bleeding reduction by systemic administration of fibrin monomer in thrombolytic therapy. Circulation pathology and cardiac surgery. 2020; 24 (1): 78–86. (In Russ.) DOI: 10.21688/1681-3472-2020-1-78-86. |
| [26] |
Вдовин В.М., Момот А.П., Орехов Д.А. и др. Минимизация посттравматического кровотечения при тромболитической терапии путём системного введения фибрина-мономера в эксперименте. Патология кровообращения и кардиохир. 2020; 24 (1): 78–86. DOI: 10.21688/1681-3472-2020-1-78-86. |
| [27] |
Ouyang C., Hwang L.J., Huang T.F. α-Fibrinogenase from Agkistrodon rhodostoma (Malayan pit viper) snake venom. Toxicon. 1983; 21 (1): 25–33. DOI: 10.1016/0041-0101(83)90046-6. |
| [28] |
Regoeczi E., Gergely J., McFarlane A.S. In vivo effects of Agkistrodon rhodostoma venom: Studies with fibrinogen-131I. J. Clin. Invest. 1966; 45 (7): 1202–1212. DOI: 10.1172/JCI105426. |
| [29] |
Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv. Chast' pervaya. (Guidelines for preclinical drug trial. Part 1.) Ed. by A.N. Mironova. Moscow: Grif and K. 2012; 941 р. (In Russ.) |
| [30] |
Руководство по проведению доклинических исследований лекарственных средств. Часть первая. Под ред. А.Н. Миронова. М.: Гриф и К. 2012; 941 с. |
| [31] |
Khabriev R.U. Rukovodstvo po eksperimental'nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv. (Guidelines for experimental (preclinical) study of new pharmacological substances.) 2-nd ed., Moscow: Meditsina. 2005; 828 p. (In Russ.) |
| [32] |
Хабриев Р.У. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. Изд. 2-е, перераб. и доп. М.: Медицина. 2005; 828 с. |
| [33] |
Vdovin V.M., Momot A.P., Orekhov D.A. et al. Time-dependent systemic hemostatic effects of fibrin monomer in controlled liver injury in the experiment. Kazan Medical Journal. 2019; 100 (2): 257–263. (In Russ.) DOI: 10.17816/KMJ2019-257. |
| [34] |
Вдовин В.М., Момот А.П., Орехов Д.А. и др. Время-зависимые системные гемостатические эффекты фибрина-мономера при дозированной травме печени в эксперименте. Казанский мед. ж. 2019; 100 (2): 257–263. DOI: 10.17816/KMJ2019-257. |
| [35] |
Spravochnik. Fiziologicheskie, biokhimicheskie i biometricheskie pokazateli normy eksperimental'nykh zhivotnykh. (Resource guide. Normal physiological, biochemical and biometric parameters in experimental animals.) Ed. by V.G. Makarova. St. Petersburg: LEMA. 2013; 116 р. (In Russ.) |
| [36] |
Справочник. Физиологические, биохимические и биометрические показатели нормы экспериментальных животных. Под ред. В.Г. Макарова. СПб.: ЛЕМА. 2013; 116 с. |
| [37] |
Kopaladze R.A. Methods of euthanasia of experimental animals. Ethics, esthetics and personnel safety. Achievements of physiological sciences. 2000; 31 (3): 79–90. (In Russ.) |
| [38] |
Копаладзе Р.А. Методы эвтаназии экспериментальных животных. Этика, эстетика, безопасность персонала. Успехи физиол. наук. 2000; 31 (3): 79–90. |
| [39] |
Barkagan Z.S., Momot A.P. Diagnostika i kontroliruemaya terapiya narushenij gemostaza. (Diagnostics and controlled therapy of the hemostatic system.) Moscow: N`yudiamed. 2008; 283 p. (In Russ.) |
| [40] |
Баркаган З.С., Момот А.П. Диагностика и контролируемая терапия системы гемостаза. М.: Ньюдиамед. 2008; 283 с. |
| [41] |
Barkagan Z.S., Glazunova G.A., Taranina T.S. Comparative Study of the development of various toxigenic syndromes of disseminated intravascular coagulation. Patologicheskaya fiziologiya i eksperimental'naya terapiya. 1988; (2): 67–70. (In Russ.) |
| [42] |
Баркаган З.С., Глазунова Г.А., Таранина Т.С. Сравнительное изучение особенностей развития различных токсигенных синдромов диссеминированного внутрисосудистого свёртывания крови. Патол. физиол. и эксперим. терап. 1988; (2): 67–70. |
| [43] |
Rukovodstvo po gematologii. (Hematology guidelines.) Ed. by A.I. Vorob'ev. 3nd ed. Vol. 3. Moscow: N`yudiamed. 2005; 416 р. (In Russ.) |
| [44] |
Руководство по гематологии. Под. ред. А.И. Воробьёва. Изд. 3-е, перераб. и доп. Т. 3. М.: Ньюдиамед. 2005; 416 с. |
| [45] |
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. Bulletin of siberian medicine. 2020; 19 (1): 36–42. (In Russ.) DOI: 10.20538/1682-0363-2020-1-36–42. |
| [46] |
Вдовин В.М., Момот А.П., Орехов Д.А. и др. Системные гемостатические эффекты фибрина-мономера при ингибировании агрегационной функции тромбоцитов в эксперименте. Бюлл. сибирской мед. 2020; 19 (1): 36–42. DOI: 10.20538/1682-0363-2020-1-36–42. |
Vdovin V.M., Momot A.P., Orekhov D.A., Shakhmatov I.I., Lycheva N.A., Momot D.A.
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