fibrin glue

{{Infobox drug

| type = combo

| image = Glued IOL Fig 9.jpg

| width =

| alt =

| caption = Fibrin glue applied after drying the scleral bed in an intraocular lens operation

| component1 = Fibrinogen

| class1 = Glycoprotein

| component2 = Thrombin

| class2 = Coagulation factor

| pronounce =

| tradename = Artiss, Evicel, Tisseel, others

| Drugs.com = {{Drugs.com|ppa|fibrin-sealant}}

| MedlinePlus =

| DailyMedID = Fibrinogen

| pregnancy_AU = B2

| pregnancy_AU_comment = {{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=12 May 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=13 May 2022}}

| pregnancy_category=

| routes_of_administration = Topical

| ATC_prefix = B02

| ATC_suffix = BC30

| ATC_supplemental =

| legal_AU = S4

| legal_AU_comment = {{cite web | title=VeraSeal | website=Therapeutic Goods Administration (TGA) | date=12 November 2021 | url=https://www.tga.gov.au/apm-summary/veraseal | access-date=28 December 2021}}{{cite web | title=AusPAR: Human Fibrinogen / Human Thrombin | website=Therapeutic Goods Administration (TGA) | date=29 June 2022 | url=https://www.tga.gov.au/auspar/auspar-human-fibrinogen-human-thrombin-0 | access-date=17 July 2022}}

| legal_BR =

| legal_BR_comment =

| legal_CA = Rx-only

| legal_CA_comment = /{{nbsp}}Schedule D{{cite web | title=Health product highlights 2021: Annexes of products approved in 2021 | website=Health Canada | date=3 August 2022 | url=https://www.canada.ca/en/health-canada/services/publications/drugs-health-products/health-product-highlights-2021/appendices.html | access-date=25 March 2024}}

| legal_DE =

| legal_DE_comment =

| legal_NZ =

| legal_NZ_comment =

| legal_UK = POM

| legal_UK_comment = {{cite web | title=TachoSil sealant matrix - Summary of Product Characteristics (SmPC) | website=(emc) | date=31 January 2020 | url=https://www.medicines.org.uk/emc/product/119/smpc | access-date=10 July 2020 | archive-date=10 July 2020 | archive-url=https://web.archive.org/web/20200710030954/https://www.medicines.org.uk/emc/product/119/smpc | url-status=dead }}{{cite web | title=Tisseel Ready to use Solutions for Sealant - Summary of Product Characteristics (SmPC) | website=(emc) | date=30 December 2019 | url=https://www.medicines.org.uk/emc/product/1801/smpc | access-date=10 July 2020}}{{cite web | title=Artiss Solutions for Sealant - Summary of Product Characteristics (SmPC) | website=(emc) | date=29 January 2019 | url=https://www.medicines.org.uk/emc/product/1800/smpc | access-date=10 July 2020}}

| legal_US = Rx-only

| legal_US_comment = {{cite web | title=Vistaseal | website=U.S. Food and Drug Administration (FDA) | date=1 October 2024 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vistaseal | archive-url=https://web.archive.org/web/20220705212747/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/vistaseal | url-status=dead | archive-date=5 July 2022 | access-date=2 October 2024}}{{cite web | title=Artiss Fibrin Sealant- fibrinogen human, human thrombin solution | website=DailyMed | date=9 June 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=92fc93e1-9695-4705-90c5-4452a80bb074 | access-date=2 October 2024}}{{cite web | title=Tisseel Fibrin Sealant- fibrinogen human, human thrombin kit; Tisseel Fibrin Sealant- fibrinogen human, human thrombin solution | website=DailyMed | date=26 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b3f69e25-1b87-4507-81fa-582ea084673d | access-date=2 October 2024}}{{cite web | title=TachoSil | website=U.S. Food and Drug Administration | date=1 October 2024 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/tachosil | archive-url=https://web.archive.org/web/20190930051605/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/tachosil | url-status=dead | archive-date=30 September 2019 | access-date=2 October 2024}}

| legal_EU = Rx-only

| legal_EU_comment = {{cite web | title=Veraseal EPAR | website=European Medicines Agency (EMA) | date=10 November 2017 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/veraseal-0 | access-date=13 September 2024}}

| legal_UN =

| legal_UN_comment =

| legal_status = Rx-only

| CAS_number =

| CAS_supplemental =

| PubChem =

| IUPHAR_ligand =

| DrugBank =

| ChemSpiderID =

| UNII =

| KEGG = D12591

| ChEBI =

| ChEMBL =

| NIAID_ChemDB =

| PDB_ligand =

| synonyms =

}}

Fibrin glue (also called fibrin sealant) is a surgical formulation used to create a fibrin clot for hemostasis, cartilage repair surgeries or wound healing. It contains separately packaged human fibrinogen and human thrombin.{{cite journal | vauthors = Irwin RM, Bonassar LJ, Cohen I, Matuska AM, Commins J, Cole B, Fortier LA | title = The clot thickens: Autologous and allogeneic fibrin sealants are mechanically equivalent in an ex vivo model of cartilage repair | journal = PLOS ONE | volume = 14 | issue = 11 | pages = e0224756 | date = 8 November 2019 | pmid = 31703078 | pmc = 6839864 | doi = 10.1371/journal.pone.0224756 | doi-access = free | bibcode = 2019PLoSO..1424756I }}{{cite journal | vauthors = Shah NV, Meislin R | title = Current state and use of biological adhesives in orthopedic surgery | journal = Orthopedics | volume = 36 | issue = 12 | pages = 945–956 | date = December 2013 | pmid = 24579215 | doi = 10.3928/01477447-20131120-09 }}{{Cite journal | vauthors = Smith BL, Matuska AM, Greenwood VL, Gilat R, Wijdicks CA, Cole BJ |date=15 April 2022 |title=Autologous Fibrin Sealants Have Comparable Graft Fixation to an Allogeneic Sealant in a Biomechanical Cadaveric Model of Chondral Defect Repair |journal=Arthroscopy, Sports Medicine, and Rehabilitation |volume=4 |issue=3 |pages=e1075–e1082 |language=English |doi=10.1016/j.asmr.2022.03.003 |pmid=35747626 |pmc=9210474 |s2cid=248208731 |issn=2666-061X}}{{cite journal | vauthors = Atrah HI | title = Fibrin glue | journal = BMJ | volume = 308 | issue = 6934 | pages = 933–934 | date = April 1994 | pmid = 8173397 | pmc = 2539755 | doi = 10.1136/bmj.308.6934.933 }}{{cite journal | vauthors = Thompson DF, Letassy NA, Thompson GD | title = Fibrin glue: a review of its preparation, efficacy, and adverse effects as a topical hemostat | journal = Drug Intelligence & Clinical Pharmacy | volume = 22 | issue = 12 | pages = 946–952 | date = December 1988 | pmid = 2468466 | doi = 10.1177/106002808802201203 | s2cid = 37017252 | doi-access = free }}{{cite web | url = http://www.medhelp.org/forums/gastro/archive/1054.html | title = Fibrin Glue for Anal Fistula - Digestive Disorders / Gastroenterology | work = MedHelp }}{{cite journal | vauthors = Shinohara K, Kobayashi E, Yoshida T, Toyama N, Kiyozaki H, Fujimura A, Miyata M | title = Effect of fibrin glue on small and large bowel anastomoses in the rat | journal = European Surgical Research | volume = 30 | issue = 1 | pages = 8–12 | year = 1998 | pmid = 9493689 | doi = 10.1159/000008552 | s2cid = 46792418 }}{{cite journal | vauthors = Spotnitz WD, Mintz PD, Avery N, Bithell TC, Kaul S, Nolan SP | title = Fibrin glue from stored human plasma. An inexpensive and efficient method for local blood bank preparation | journal = The American Surgeon | volume = 53 | issue = 8 | pages = 460–462 | date = August 1987 | pmid = 2440358 }}{{cite journal | url = http://www.ijps.org/article.asp?issn=0970-0358;year=2003;volume=36;issue=1;spage=14;epage=17;aulast=Saxena |title=Preparation of two component Fibrin Glue and its clinical evaluation in skin grafts and flaps |year=2003 |volume=36 |issue=1 |pages=14–17 |vauthors=Saxena S, Jain P, Shukla J|journal= Indian J Plast Surg|doi=10.1055/s-0043-1778572 |doi-access=free }}{{cite journal | vauthors = Mücke T, Wolff KD | title = Performing microvascular anastomosis with fibrin glue--faster, easier, and more reliable? | journal = Microsurgery | volume = 29 | issue = 1 | pages = 80–81 | year = 2009 | pmid = 18946885 | doi = 10.1002/micr.20556 | s2cid = 31854904 }}

Medical uses

This glue is used as a supportive treatment in surgery (such as liver surgery) for the improvement of hemostasis where standard surgical techniques are insufficient or impractical.{{cite web | title=Evicel Fibrin Sealant (Human) | website=U.S. Food and Drug Administration (FDA) | date=22 July 2017 | url=https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/evicel | archive-url=https://web.archive.org/web/20190930051347/https://www.fda.gov/vaccines-blood-biologics/approved-blood-products/evicel | url-status=dead | archive-date=30 September 2019 }}

It is also used for repairing dura mater tears and bronchial fistulas and for achieving hemostasis after spleen and liver trauma, in "no sutures" corneal transplantation, pterygium excision with amniotic membrane or conjunctival autograft, and in eye trauma for corneal or conjunctival defects,{{cite journal | vauthors = Narendran N, Mohamed S, Shah S | title = No sutures corneal grafting--a novel use of overlay sutures and fibrin glue in Deep Anterior Lamellar Keratoplasty | journal = Contact Lens & Anterior Eye | volume = 30 | issue = 3 | pages = 207–209 | date = July 2007 | pmid = 17379570 | doi = 10.1016/j.clae.2007.02.007 }}{{cite journal | vauthors = Dal Pizzol MM, Roggia MF, Kwitko S, Marinho DR, Rymer S | title = [Use of fibrin glue in ocular surgery] | language = pt | journal = Arquivos Brasileiros de Oftalmologia | volume = 72 | issue = 3 | pages = 308–312 | year = 2009 | pmid = 19668958 | doi = 10.1590/s0004-27492009000300006 | trans-title = Use of fibrin glue in ocular surgery | doi-access = free | hdl = 10183/37501 | hdl-access = free }}{{cite web|url=http://www.vivostat.com/products/vivostat-fibrin-sealant|title=Fibrin Sealant Fibrin Gluing Haemostasis autologous|publisher=vivostat.com}} as well as for skin graft donor site wounds to reduce postoperative pain.{{cite journal | vauthors = Sinha S, Schreiner AJ, Biernaskie J, Nickerson D, Gabriel VA | title = Treating pain on skin graft donor sites: Review and clinical recommendations | journal = The Journal of Trauma and Acute Care Surgery | volume = 83 | issue = 5 | pages = 954–964 | date = November 2017 | pmid = 28598907 | doi = 10.1097/TA.0000000000001615 | s2cid = 44520644 }}

It can also be used to treat pilonidal sinus disease but it is of unclear benefit as of 2017, due to insufficient research.{{cite journal | vauthors = Lund J, Tou S, Doleman B, Williams JP | title = Fibrin glue for pilonidal sinus disease | journal = The Cochrane Database of Systematic Reviews | volume = 1 | pages = CD011923 | date = January 2017 | issue = 1 | pmid = 28085995 | pmc = 6464784 | doi = 10.1002/14651858.CD011923.pub2 }}

Contraindications

The glue must not get into blood vessels, as this could lead to clotting in the form of thromboembolism or disseminated intravascular coagulation, or to anaphylaxis (a severe allergic reaction).{{cite web|title=Evicel: EPAR – Product Information|publisher=European Medicines Agency|url=https://www.ema.europa.eu/en/documents/product-information/evicel-epar-product-information_en.pdf|date=12 June 2020}}

Side effects

Possible adverse effects include bleeding disorder and allergic reactions such as flushing, stinging, generalised urticaria, angioedema, bronchospasm, and anaphylaxis. Other adverse effects in studies occurred in roughly equal proportions in treatment and placebo groups.

Interactions

As fibrin glue contains proteins, it may be denatured by ethanol, iodine and heavy metals. These substances are frequently found in antiseptic solutions.

Pharmacology

=Mechanism of action=

Thrombin is an enzyme that splits fibrinogen into fibrin monomers in 10 to 60 seconds, which aggregate to form a three-dimensional gel-like structure. Thrombin also activates factor XIII from the human body to factor XIIIa, which then cross-links the fibrin monomers to form a stable clot. Both these processes need calcium to work. As the wound heals, the clot is slowly degraded by the enzyme plasmin.{{cite journal | vauthors = Spotnitz WD | title = Fibrin sealant: past, present, and future: a brief review | journal = World Journal of Surgery | volume = 34 | issue = 4 | pages = 632–634 | date = April 2010 | pmid = 19820991 | doi = 10.1007/s00268-009-0252-7 | s2cid = 20760524 }}

=Pharmacokinetics=

In rabbit studies, only 1 to 2% of the applied thrombin dose reached the bloodstream. It reached highest blood plasma concentrations after 6 to 8 hours.

Chemistry

=Composition=

Fibrin glue comes in two vials, respectively containing:

fibrinogen: lyophilised pooled human concentrate
thrombin: This used to be of bovine origin; modern formulations contain human thrombin.

The two components are mixed immediately before application.{{cite web | title=Evicel EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/evicel | access-date=12 June 2020}} {{PD-notice}}{{cite web | title=Evicel Fibrin Sealant (Human)- fibrinogen human and thrombin human kit | website=DailyMed | date=17 December 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=31dc7ff6-bdd8-4e65-897b-109b6f8316b6 | access-date=12 June 2020}} The formulations also contain calcium salts.

Formulations from different manufacturers may also contain aprotinin, fibronectin, plasminogen, and factor XIII.{{cite web | url = http://www.fass.se/LIF/produktfakta/artikel_produkt.jsp?NplID=19950119000010&DocTypeID=5 | title = Tisseel | work = Swedish official drug catalog }}[https://www.kegg.jp/dbget-bin/www_bget?dr:D08812 KEGG drug: Factor XIII with fibrinogen]. Accessed 9 July 2020.

Legal status

A formulation with human thrombin was approved for medical use in the United States in March 2003, and in the European Union in October 2008.{{cite web | title=Evicel | website=U.S. Food and Drug Administration (FDA) | date=5 June 2017 | archive-date=22 July 2017 | url=https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm089269.htm | archive-url=https://wayback.archive-it.org/7993/20170722071419/https://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/FractionatedPlasmaProducts/ucm089269.htm | access-date=12 June 2020 | url-status=dead }}

References

Category:Blood

Category:Surgery

Category:Adhesives