|Generate QR code
Open Access
Subscription Access
Clinical application of fi brin sealant
https://doi.org/10.30629/0023-2149-2025-103-3-187-195
Abstract
Fibrin sealants in surgery has been used for a long time as a tool for hemostasis and perioperative bleeding preventing. The appropriateness of fi brin glue to diff erent surgical strategies infl uences the clinical outcome. Numerous studies on biological and synthetic adhesive compositions show that there is still limited data on how diff erences in fi brin sealant formulations relate to their clinical eff ectiveness and safety. The review is an attempt to summarize information on biological adhesives including the history of implementation of fi brin glue in surgery, gelation and adhesion mechanisms that determine the bioadhesive properties and sealing functions, the development of adhesive composition formulations, and the reasons prompting researchers to new solutions are also discussed. Alternative technologies, their advantages and disadvantages taking into account surgical strategies, are considered
About the Authors
O. K. Kvan
National Medical Research Center for Neurosurgery named after Academician N.N. Burdenko
Russian Federation
Russian Federation
Oksana K. Kvan — Head of Clinical and Productional Transfusion Department
Moscow
N. B. Teryaeva
National Medical Research Center for Neurosurgery named after Academician N.N. Burdenko
Russian Federation
Russian Federation
Nadezhda B. Teryaeva — PhD, сlinical laboratory diagnostics doctor
Moscow
References
1. Shatokhina N.A., Zhukov S.V., Morozov A.M., Mnoyan A.Kh., Muravlyantseva M.M., Ryzhova T.S., Belyak M.A. On the problem of the use of hemostatic agents in surgical practice. Modern problems of science and education. 2022;1:83–93. (In Russian). DOI: 10.17513/spno.31488
2. Demina N.B., Chernova L.V., Kozlova J.M. Application of adhesive compositions in surgery. Surgery. The N.I. Pirogov Magazine. 2019;(3):129–134. (In Russian). DOI: 10.17116/hirurgia2019031129
3. Ghosh S., Gayen P., Jan S., Kishore A.V., Kumar V., Mallick A.M., Mukherjee A., Nandi S.K., Sinha Roy R. Bioinspired Non-Immunogenic Multifunctional Sealant for Efficient Blood Clotting and Suture-Free Wound Closure. ACS Biomater. Sci. Eng. 2020;6(11):6378–6393. DOI: 10.1021/acsbiomaterials.0c01254
4. Burnouf T., Goubran H.A., Chen T.M., Ou K.L., El-Ekiaby M., Radosevic M. Blood-derived biomaterials and platelet growth factors in regenerative medicine. Blood Rev. 2013; 27(2):77–89. DOI: 10.1016/j.blre.2013.02.001
5. Burnouf T., Su. C.Y., Radosevich M., Goubran H. and El-Ekiaby M. Blood-derived biomaterials: fibrin sealant, platelet gel and platelet fibrin glue. ISBT Science Series. 2009; 4:136–142. DOI: 10.1111/j.1751-2824.2009.01222.x
6. Buchta C., Hedrich H.C., Macher M., Höcker P., Redl H. Biochemical characterization of autologous fibrin sealants produced by CryoSeal and Vivostat in comparison to the homologous fibrin sealant product Tissucol/Tisseel. Biomaterials. 2005;26(31):6233–41. DOI: 10.1016/j.biomaterials.2005.04.014
7. Bergel S. Ueber Wirkungen des Fibrins. Dtsch Med Wochenschr.1909;35(15):663–665. DOI: 10.1055/s-0029-1201395
8. Grey E.G. Fibrin as a hemostatic in cerebral surgery. Surg. Gynecol. Obstet. 1915;21:452–454.
9. Harvey S.C. The use of fibrin paper and forms in cerebral surgery. Boston Medical and Surgical J. 1916;174:658–659.
10. Cronkite E.P., Lozner E.L., Deaver J.M. Use of thrombin and fibrinogen in skin grafting: preliminary report. JAMA. 1944;124(14):976– 978. DOI: 10.1001/jama.1944.02850140022006
11. Tidrick R.T., Warner E.D. Fibrin fixation of skin transplants. Surgery. 1944;15:90–95. DOI: 10.5555/uri:pii:S0039606044900528
12. Cohn E.J., Strong L.E. Hughes W.L., Mulford D.J., Ashworth J.N., Melin M., Taylor H.L. Preparation and properties of serum and plasma proteins; a system for the separation into fractions of the protein and lipoprotein components of biological tissues and fl uids. J. Am. Chem. Soc. 1946;68(3):459–475. DOI: 10.1021/ja01207a034
13. Matras H. The use of fibrin sealant in oral and maxillofacial surgery. J. Oral Maxillofac. Surg. 1982;40(10):617–22. DOI: 10.1016/0278-2391(82)90108-2
14. Gugerell A., Schossleitner K., Wolbank S., Nürnberger S., Redl H., Gulle H., Goppelt A., Bittner M., Pasteiner W. High thrombin concen trations in fibrin sealants induce apoptosis in human keratinocytes. J. Biomed. Mater. Res. A. 2012;100(5):1239–47. DOI: 10.1002/jbm.a.34007
15. Cheng C.M., Meyer-Massetti C., Kayser S.R. A review of three stand-alone topical thrombins for surgical hemostasis. Clin. Ther. 2009;31(1):32–41. DOI: 10.1016/j.clinthera.2009.01.005
16. Bhandari M., Ofosu F.A., Mackman N., Jackson C., Doria C., Humphries J.E. et al. Safety and efficacy of thrombin-JMI: a multidisciplinary expert group consensus. Clin. Appl. Thromb. Hemost. 2011;17(1):39–45. DOI: 10.1177/1076029610385674
17. Paulmier P. The main problem with biological products of animal origin. Biologicals. 2000;28(1):55. DOI: 10.1006/biol.1999.0237
18. Spotnitz W. Fibrin sealant patches: powerful and easy-to-use hemostats. Open Access Surgery. 2014;7:71–79. DOI: 10.2147/OAS. S41516.
19. Reiner A.P. Fibrin glue increasingly popular for topical surgical hemostasis. Laboratory Medicine. 1999;30(3):189–193. DOI: 10.1093/labmed/30.3.189 .
20. Pavie A., Szefner J., Leger P., Gandjbakhch I. Preventing, minimizing, and managing postoperative bleeding. Ann. Thorac. Surg. 1999;68(2):705–10. DOI: 10.1016/s0003-4975(99)00628-1
21. Scognamiglio F., Travan A., Rustighi I., Tarchi P., Palmisano S., Marsich E. et al. Adhesive and sealant interfaces for general surgery applications. J. Biomed. Mater. Res. B Appl. Biomater. 2016;104(3):626–39. DOI: 10.1002/jbm.b.33409
22. Pipan C.M., Glasheen W.P., Matthew T.L., Gonias S.L., Hwang L.J., Jane J.A., Spotnitz W.D. Eff ects of antifibrinolytic agents on the life span of fibrin sealant. J. Surg. Res. 1992;53(4):402–7. DOI: 10.1016/0022-4804(92)90068-b
23. Smith J.D., Chen A., Ernst L.A., Waggoner A.S., Campbell P.G. Immobilization of aprotinin to fibrinogen as a novel method for controlling degradation of fibrin gels. Bioconjug. Chem. 2007;18(3):695– 701. DOI: 10.1021/bc060265o
24. Beudert M., Gutmann M., Lühmann T., Meinel L. Fibrin sealants: challenges and solutions. ACS Biomater. Sci. Eng. 2022;8(6):2220– 2231.
25. Tredree R., Beierlein W., Debrix I., Eisert A., Goff redo F., de Salazar E.G. et al. Evaluating the diff erences between fibrin sealants: recommendations from an international advisory panel of hospital pharmacists. Eur. J. Hosp. Pharm. 2006;12(1):3–9.
26. Lorentz K.M., Kontos S., Frey P., Hubbell J.A. Engineered aprotinin for improved stability of fibrin biomaterials. Biomaterials. 2011;32(2):430–438. DOI: 10.1016/j.biomaterials.2010.08.109
27. Shaff rey C.I., Spotnitz W.D., Shaff rey M.E., Jane J.A. Neurosurgical applications of fibrin glue: augmentation of dural closure in 134 patients. Neurosurgery. 1990;26(2):207–10.
28. Nakamura H., Matsuyama Y., Yoshihara H et al. The eff ect of autologous fibrin tissue adhesive on postoperative cerebrospinal fl uid leak in spinal cord surgery: a randomized controlled trial. Spine. 2005;30(13):E347–51. DOI: 10.1097/01.brs.0000167820.54413.8e
29. Lassen M.R., Solgaard S., Kjersgaard AG., Olsen C., Lind B., Mittet K., Ganes H.C. A pilot study of the eff ects of Vivostat patient-derived fibrin sealant in reducing blood loss in primary hip arthroplasty. Clin. Appl. Thromb. Hemost. 2006;12(3):352–7. DOI: 10.1177/1076029606291406
30. Fischer C.P., Wood C.G., Shen J., Batiller J., Hart J.C., Patel B., Albala D.M. A randomized trial of aprotinin-free fibrin sealant versus absorbable hemostat. Clin. Appl. Thromb. Hemost. 2011;17(6):572-7. DOI: 10.1177/1076029611404212
31. Guterl CC., Torre O.M., Purmessur D., Dave K., Likhitpanichkul M., Hecht A.C., Nicoll S.B, Iatridis J.C. Characterization of mechanics and cytocompatibility of fibrin-genipin annulus fibrosus sealant with the addition of cell adhesion molecules. Tissue Eng. Part A. 2014;20(17–18):2536–45. DOI: 10.1089/ten.TEA.2012.0714
32. Loenko Yu.N., Artyukov A.A., Lyamkin G.P., Glazkova V.E., Prutskova T.A. Lectins and agglutinins of marine algae. Rast. resources. 1990:26(2):263–274. (In Russian).
33. Scognamiglio F., Travan A., Rustighi I., Tarchi P., Palmisano S., Marsich E., Borgogna M., Donati I., de Manzini N., Paoletti S. Adhesive and sealant interfaces for general surgery applications. J. Biomed. Mater. Res. B Appl. Biomater. 2016;104(3):626–39. DOI: 10.1002/jbm.b.33409
34. Deslys J., Comoy E., Hawkins S. et al. Screening slaughtered cattle for BSE. Nature. 2001;409(25):476–478.
35. Schwarz T.F. Ubertragung von parvovirus B19 durch blut und blutkomponenten (German). [Transmission of parvovirus B19 by blood and blood components]. Infusionsther Transfusionsmed. 1994;21(1):27–31.
36. Ham S.W., Lew W.K., Weaver F.A. Thrombin use in surgery: an evidence-based review of its clinical use. J Blood Med. 2010;1:135-42. DOI: 10.2147/JBM.S6622. Epub 2010 Jul 22. Retraction in: J. Blood Med. 2022;13:165-166.
37. Lopez M.J., Yandrapalli S. Thrombin. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. URL: https://www.ncbi.nlm.nih.gov/books/NBK557836.
38. Wilson S.M., Pell P. Donegan E.A. HIV-1 Transmission Following the Use of Cryoprecipitate Fibrinogen as Gel/Adhesive. Transfusion. 1991;31:51S.
39. Bänninger H., Hardegger T., Tobler A., Barth A., Schüpbach P., Reinhart W., Lämmle B., Furlan M. Fibrin glue in surgery: frequent development of inhibitors of bovine thrombin and human factor V. Br. J. Haematol. 1993;85(3):528–32. DOI: 10.1111/j.1365-2141.1993.tb03343.x
40. Berruyer M., Amiral J., Ffrench P., Belleville J., Bastien O., Clerc J. et al. Immunization by bovine thrombin used with fibrin glue during cardiovascular operations. Development of thrombin and factor V inhibitors. J. Thorac. Cardiovasc. Surg. 1993;105(5):892–7.
41. Lundblad R.L., Bradshaw R.A., Gabriel D., Ortel T.L., Lawson J., Mann K.G. A review of the therapeutic uses of thrombin. Thromb. Haemost. 2004;91(5):851–60. DOI: 10.1160/TH03-12-0792
42. Ness P., Creer M., Rodgers G.M., Naoum J.J., Renkens K., Voils S.A., Alexander W.A. Recognition, evaluation and treatment of acquired coagulopathy consensus (RETACC) panel. Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety. Patient Saf. Surg. 2009;3(1):8. DOI: 10.1186/1754-9493-3-8
43. Zehnder J.L., Leung L.L. Development of antibodies to thrombin and factor V with recurrent bleeding in a patient exposed to topical bovine thrombin. Blood. 1990;76(10):2011–6.
44. Bishop P.D., Lewis K.B., Schultz J., Walker K.M. Comparison of recombinant human thrombin and plasma-derived human alpha-thrombin. Semin. Thromb. Hemost. 2006;32(1):86–97. DOI: 10.1055/s-2006-939558
45. Croxtall J.D., Scott L.J. Recombinant human thrombin: in surgical hemostasis. BioDrugs. 2009;23(5):333–8. DOI: 10.2165/11202650-000000000-00000
46. Han B., Woodell-May J., Ponticiello M., Yang Z., Nimni M. The eff ect of thrombin activation of platelet-rich plasma on demineralized bone matrix osteoinductivity. J. Bone Joint Surg. Am. 2009;91(6):1459–70. DOI: 10.2106/JBJS.H.00246
47. LeBlanc H., Ashkenazi A. Apo2L/TRAIL and its death and decoy receptors. Cell Death Diff er. 2003:10:66–75. DOI: 10.1038/sj.cdd.4401187
48. Reichsöllner R., Heher P., Hartmann J. A comparative high-resolution physicochemical analysis of commercially available fibrin sealants: Impact of sealant osmolality on biological performance. 2022. Journal of Biomedical Materials Research. 2022;111(4):488– 501DOI:10.1002/jbm.a.37466.
49. Bell W.R. Jr. Defibrinogenating enzymes. Drugs. 1997;54(3):18–30; discussion 30–1. DOI: 10.2165/00003495-199700543-00005
50. Velada J.L., Hollingsbee D.A., Menzies A.R., Cornwell R., Dodd R.A. Reproducibility of the mechanical properties of Vivostat system patient-derived fibrin sealant. Biomaterials. 2002;23(10):2249–54. DOI: 10.1016/s0142-9612(01)00359-3
51. Bordon K.C.F., Cologna C.T., Fornari-Baldo E.C., Pinheiro-Júnior E.L., Cerni F.A., Amorim F.G. et al. From animal poisons and venoms to medicines: achievements, challenges and perspectives in drug discovery. Front Pharmacol. 2020 24;11:1132. DOI: 10.3389/fphar.2020.01132
52. Vu T.T., Staff ord A.R., Leslie B.A., Kim P.Y., Fredenburgh J.C., Weitz J.I. Batroxobin binds fibrin with higher affinity and promotes clot expansion to a greater extent than thrombin. J. Biol. Chem. 2013;288(23):16862–16871. DOI: 10.1074/jbc.M113.464750
53. Mosesson M.W., Siebenlist K.R., Meh D.A. The structure and biological features of fibrinogen and fibrin. Ann. N.-Y. Acad. Sci. 2001;936:11–30. DOI: 10.1111/j.1749-6632.2001.tb03491.x
54. Kjaergard H.K., Fairbrother J.E. Controlled clinical studies of fibrin sealant in cardiothoracic surgery — a review. Eur. J. Cardiothorac. Surg. 1996;10(9):727–33. DOI: 10.1016/s1010-7940(96)80332-0
55. Rousou J., Levitsky S., Gonzalez-Lavin L., Cosgrove D., Magilligan D., Weldon C. et al. Randomized clinical trial of fibrin sealant in patients undergoing resternotomy or reoperation after cardiac operations. A multicenter study. J. Thorac. Cardiovasc. Surg. 1989;97(2):194–203.
56. Berg P.L., Barina W., Born P. Endoscopic injection of fibrin glue versus polidocanol in peptic ulcer hemorrhage: a pilot study. Endoscopy. 1994;26(6):528–30. DOI: 10.1055/s-2007-1009028
57. Fibrin Sealants Market, By Product Type (Liquid Fibrin Sealants and Patch-based Fibrin Sealants), By Application (General Surgery, Cardiovascular Surgery, Orthopedic Surgery, Neurosurgery, and Others), and By Region Forecast to 2032. Pharma and Healthcare — Fibrin Sealants Market. URL: https://www.reportsanddata.com/report-detail/fibrin-sealants-market
58. Shaff rey C.I., Spotnitz W.D., Shaff rey M.E., Jane J.A. Neurosurgical applications of fibrin glue: augmentation of dural closure in 134 patients. Neurosurgery. 1990;26(2):207–10.
59. Arnautovic K.I., Kovacevic M. CSF-Related Complications After Intradural Spinal Tumor Surgery: Utility of an Autologous Fat Graft. Medical Archives (Sarajevo, Bosnia and Herzegovina). 2016;70(6):460–465. DOI: 10.5455/medarh.2016.70.460-465. PMID: 28210022
60. Lars Poulsgaard, Anette Mørck, Niels Erik Holm. A Safety Study of the Use of Vivostat® Patient-Derived Fibrin Sealant Containing Tranexamic Acid in Neurosurgery. Skull Base Surgery. 2007;17:A023. DOI: 10.1055/s-2007-981728
61. Koea J., Baldwin P., Shen J., Patel B., Batiller J., Arnaud A. et al. Safety and hemostatic eff ectiveness of the fibrin pad for severe soft-tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic (non-cardiac) surgery: a randomized, controlled, superiority trial. World J. Surg. 2015;39(11):2663–9. DOI: 10.1007/s00268-015-3106-5
62. Graziano F., Certo F., Basile L., Maugeri R., Grasso G., Meccio F., Ganau M., Iacopino D.G. Autologous fibrin sealant (Vivostat(®)) in the neurosurgical practice: Part I: Intracranial surgical procedure. Surg. Neurol. Int. 2015;6:77. DOI: 10.4103/2152-7806.156871
63. Fukumoto T., Matsushima Y., Tomita S., Inaba Y. The use of fibrin glue in neurosurgical operations. No Shinkei Geka. 1985;13(4): 367–73.
64. Graziano F., Maugeri R., Basile L., Meccio F., Iacopino D.G. Aulogous fibrin sealant (Vivostat(®)) in the neurosurgical practice: Part II: Vertebro-spinal procedures. Surg. Neurol. Int. 2016;7(3):S77–82. DOI: 10.4103/2152-7806.174894
65. Karmaker A., Ahmed Sh. Fibrin glue sources, characteristics and applications. in: adhesives in biomedical applications. book editor(s): K.L. Mittal, S. Neogi. 2023. DOI: 10.1002/9781394209897.ch5
66. Corral M., Ferko N., Hogan A., Hollmann S.S. A hospital cost analysis of a fibrin sealant patch in soft tissue and hepatic surgical bleeding. DOI: 10.2147/CEOR.S112762
67. Davidson B.R., Burnett S., Javed M.S., Seifalian A., Moore D., Doctor N. Experimental study of a novel fibrin sealant for achieving haemostasis following partial hepatectomy. Br. J. Surg. 2000;87(6):790–5. DOI: 10.1046/j.1365-2168.2000.01427.x
68. Harmon A.M., Kong W., Buensuceso C.S., Gorman A.J., Muench T.R. Eff ects of fibrin pad hemostat on the wound healing process in vivo and in vitro. Biomaterials. 2011;32(36):9594–601. DOI: 10.1016/j.biomaterials.2011.09.019
69. Caiado F., Carvalho T., Silva F., Castro C., Clode N., Dye J.F., Dias S. The role of fibrin E on the modulation of endothelial progenitors adhesion, diff erentiation and angiogenic growth factor production and the promotion of wound healing. Biomaterials. 2011;32(29):7096– 105. DOI: 10.1016/j.biomaterials.2011.06.022
70. Corral M., Ferko N., Hollmann S., Hogan A., Jamous N., Batiller J. Clinician reported ease of use for a novel fibrin sealant patch for hemostasis: results from four randomized controlled trials. Curr. Med. Res. Opin. 2016;32(2):367–75. DOI: 10.1185/03007995.2015.1128405
71. Fischer C.P., Bochicchio G., Shen J., Patel B., Batiller J., Hart J.C. A prospective, randomized, controlled trial of the efficacy and safety of fibrin pad as an adjunct to control soft tissue bleeding during abdominal, retroperitoneal, pelvic, and thoracic surgery. J. Am. Coll. Surg. 2013;217(3):385–93. DOI: 10.1016/j.jamcollsurg.2013.02.036
72. Koea J.B., Batiller J., Patel B., Shen J., Hammond J., Hart J., Fischer C., Garden O.J. A phase III, randomized, controlled, superiority trial evaluating the fibrin pad versus standard of care in controlling parenchymal bleeding during elective hepatic surgery. HPB (Oxford). 2013;15(1):61–70. DOI: 10.1111/j.1477-2574.2012.00583.x. –
73. Fischer C.P., Wood C.G., Shen J., Batiller J., Hart J.C., Patel B., Albala D.M. A randomized trial of aprotinin-free fibrin sealant versus absorbable hemostat. Clin. Appl. Thromb. Hemost. 2011;17(6):572– 7. DOI: 10.1177/1076029611404212
74. Giannini S., Buda R., Cavallo M., Ruffilli A., Cenacchi A., Cavallo C., Vannini F. Cartilage repair evolution in post-traumatic osteochondral lesions of the talus: from open field autologous chondrocyte to bonemarrow-derived cells transplantation. Injury. 2010;41(11):1196–203. DOI: 10.1016/j.injury.2010.09.028
75. Fontein D., Burger M., Mannil L., Giovanoli P., Plock J. Evaluation of platelet-rich fibrin in deep dermal burn: a case study. Congress of Swiss Plastic Surgery. September 2017. St. Moritz, Schwitzerland.
76. Knee surgeons at London Bridge Hospital get stuck into the use of Biological glues. London Bridge Hospital. Health Matters. 2016;18:11.
Review
For citations:
Kvan O.K., Teryaeva N.B. Clinical application of fi brin sealant. Clinical Medicine (Russian Journal). 2025;103(3):187-195. (In Russ.) https://doi.org/10.30629/0023-2149-2025-103-3-187-195
Views:
43
Email this article 