Effects of fibrinogen concentrate, factor XIII, and thrombin-activatable fibrinolysis inhibitor on clot firmness and fibrinolytic resistance in the model of hyperfibrinolysis
Keywords:
fibrinogen; factor XIII; thrombin-activatable fibrinolysis inhibitor; hyperfibrinolysis.
Abstract
Aim. To investigate effects of fibrinogen concentrate, factor XIII, and thrombin-activatable fibrinolysis inhibitor (TAFI) on clot formation and fibrinolytic resistance using an in vitro model of hyperfibrinolysis. Methods. Citrated whole blood from 24 adult healthy volunteers was supplemented with fibrinogen concentrate, factor XIII, and/or TAFI. Fibrinolysis was induced by tissue plasminogen activator. Clotting was induced by recalcification and addition of tissue factor and monitored using rotation thromboelastometry. Results. Induction of fibrinolysis did not affect clotting time and the rate of clot formation but significantly reduced the maximum clot firmness and caused lysis of a clot. Addition of fibrinogen concentrate to blood reduced the rate of clot lysis without affecting clot firmness or lysis onset time; addition of factor XIII improved clot firmness and reduced clot lysis rate without affecting lysis onset time; TAFI improved clot firmness and considerably delayed the onset of clot lysis thereby providing the greatest antifibrinolytic effect. Conclusion. Fibrinogen concentrate, factor XIII, and TAFI may potentially serve as an alternative to traditional antifibrinolytic agents and be beneficial for the treatment of patients with hyperfibrinolysis.
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References
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2. Davenport R.A., Guerreiro M., Frith D., Rourke C., Platton S., Cohen M., et al. Activated protein C drives the hyperfibrinolysis of acute traumatic coagulopathy. Anesthesiology. 2017; 126(1): 115-27.
3. Ranucci M. Hemostatic and thrombotic issues in cardiac surgery. Semin Thromb Hemost. 2015; 41(1): 84-90.
4. Wada T., Gando S., Ono Y., Maekawa K., Katabami K., Hayakawa M., et al. Disseminated intravascular coagulation with the fibrinolytic phenotype predicts the outcome of patients with out-of-hospital cardiac arrest. Thromb J. 2016; 14: 43.
5. Ferro D., Celestini A., Violi F. Hyperfibrinolysis in Liver Disease. Clin Liver Dis. 2009; 13(1): 21-31.
6. Henry D.A., Carless P.A., Moxey A.J., O’Connell D., Stokes B.J., Fergusson D.A., et al. Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion. Cochrane Database Syst Rev. 2011; (3):CD001886.
7. Wu Q., Zhang H.-A., Liu S.-L., Meng T., Zhou X., Wang P. Is tranexamic acid clinically effective and safe to prevent blood loss in total knee arthroplasty? A meta-analysis of 34 randomized controlled trials. Eur J Orthop Surg Traumatol. 2015; 25(3): 525-41.
8. Roberts I., Edwards P., Prieto D., Joshi M., Mahmood A., Ker K., et al. Tranexamic acid in bleeding trauma patients: an exploration of benefits and harms. Trials. 2017; 18(1): 48.
9. Godier A., Hunt B.J. Aprotinin as an alternative to tranexamic acid in cardiac surgery — Is this where we started from? Anaesth Crit Care Pain Med. 2017; 36(2): 79-81.
10. European Society of Anaesthesiology task force reports on place of aprotinin in clinical anaesthesia. Aprotinin: is it time to reconsider? Eur J Anaesthesiol. 2015;32(9):591-5.
11. Upadhyay S.P., Mallick P.N., Jagia M., Singh R.K.A. Acute arterial thrombosis associated with inadvertent high dose of tranexamic acid. Indian J Crit Care Med. 2013; 17(4): 237-9.
12. Silva M.M.C.G., Thelwell C., Williams S.C., Longstaff C. Regulation of fibrinolysis by C-terminal lysines operates through plasminogen and plasmin but not tissue-type plasminogen activator. J Thromb Haemost. 2012; 10(11): 2354-60.
13. Hijazi N., Abu Fanne R., Abramovitch R., Yarovoi S., Higazi M., Abdeen S., et al. Endogenous plasminogen activators mediate progressive intracerebral hemorrhage after traumatic brain injury in mice. Blood. 2015; 125(16): 2558-67.
14. Myles P.S., Smith J.A., Forbes A., Silbert B., Jayarajah M., Painter T., et al. Tranexamic Acid in Patients Undergoing Coronary-Artery Surgery. N Engl J Med. 2017; 376(2): 136-48.
15. Sharma V., Katznelson R., Jerath A., Garrido-Olivares L., Carroll J., Rao V., et al. The association between tranexamic acid and convulsive seizures after cardiac surgery: a multivariate analysis in 11 529 patients. Anaesthesia. 2014; 69(2): 124-30.
16. Bucay I., O’Brien E.T., Wulfe S.D., Superfine R., Wolberg A.S., Falvo M.R., et al. Physical determinants of fibrinolysis in single fibrin fibers. PloS One. 2015; 10(2):e0116350.
17. Weisel J.W., Litvinov R.I. Fibrin Formation, Structure and Properties. Subcell Biochem. 2017; 82: 405-56.
18. Godier A., Parmar K., Manandhar K., Hunt B.J. An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis. J Clin Pathol. 2017; 70(2): 154-61.
19. Hur W.S., Mazinani N., Lu X.J.D., Britton H.M., Byrnes J.R., Wolberg A.S. et al. Coagulation factor XIIIa is inactivated by plasmin. Blood. 2015; 126(20): 2329-37.
20. Kim P.Y., Stewart R.J., Lipson S.M., Nesheim M.E. The relative kinetics of clotting and lysis provide a biochemical rationale for the correlation between elevated fibrinogen and cardiovascular disease. J Thromb Haemost. 2007; 5(6): 1250-6.
21. Sabate A., Gutierrez R., Beltran J., Mellado P., Blasi A., Acosta F. et al. Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial. Am J Transplant. 2016; 16(8): 2421-9.
22. Hethershaw E.L., Cilia La Corte A.L., Duval C., Ali M., Grant P.J., Ariеns R.A.S. et al. The effect of blood coagulation factor XIII on fibrin clot structure and fibrinolysis. J Thromb Haemost. 2014; 12(2): 197-205.
23. Rijken D.C., Abdul S., Malfliet J.J.M.C., Leebeek F.W.G., Uitte de Willige S. Compaction of fibrin clots reveals the antifibrinolytic effect of factor XIII. J Thromb Haemost. 2016; 14(7): 1453-61.
24. Ichinose A., Japanese Collaborative Research Group on AH13. Autoimmune acquired factor XIII deficiency due to anti-factor XIII/13 antibodies: A summary of 93 patients. Blood Rev. 2017; 31(1): 37-45.
25. Marar T.T., Boffa M.B. Identification of a thrombomodulin interaction site on thrombin-activatable fibrinolysis inhibitor that mediates accelerated activation by thrombin. J Thromb Haemost. 2016; 14(4): 772-83.
Published
2017-12-18
How to Cite
Budnik I. A., Morozova O. L., Tsymbal A. A., Shenkman B. ., Einav Y. . Effects of fibrinogen concentrate, factor XIII, and thrombin-activatable fibrinolysis inhibitor on clot firmness and fibrinolytic resistance in the model of hyperfibrinolysis // Patologicheskaya Fiziologiya i Eksperimental’naya Terapiya (Pathological physiology and experimental therapy). 2017. VOL. 61. № 4. PP. 44–50.
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Original research
