Fibrin glue

Fibrin glue consists of two main components: fibrinogen and thrombin.^1,2 These are loaded into two syringes with tips forming a common port. When injected the two components meet in equal volumes at the point of delivery. The thrombin converts the fibrinogen to fibrin by enzymatic action at a rate determined by the concentration of thrombin. The more concentrated thrombin solution produces a fibrin clot in about 10 seconds, and the more dilute thrombin solution forms the clot about 60 seconds after the glue is applied to the surgical field. Both the extrinsic and the intrinsic mechanisms of blood coagulation are bypassed, but the physiological final common pathway of coagulation is faithfully replicated. Factor XIII (present in the fibrinogen component of the glue) cross links and stabilises the clot's fibrin monomers. Some preparations of fibrin glue contain aprotinin to delay the fibrinolytic action of plasmin.3

Modern surgical techniques are efficient at securing haemostasis, but oozing of blood from multiple pinpoints on a large raw surface remains difficult to control. The use of electrocautery, sutures, or metal clips and staples may not be appropriate in delicate surgery on small yet functionally vital tissues and structures. In these settings fibrin glue is ideal for topical application to secure haemostasis. In cardiovascular and thoracic surgery, for example, fibrin glue may be sprayed with use of pressurised gas or compressed air to arrest bleeding from the surfaces of the heart, pericardium, mediastinum, and pleura.^4,5 It may be used in a similar way to form a thin film on the liver or the liver bed, or both,6 and in neurosurgical,7 ophthalmological,8 and some otolaryngological operations9; in vitro fertilisation10; and other microsurgery.11 A further obvious indication for fibrin glue is external oozing of blood in patients with haemophilia.12 Fibrin glue is not, however, a substitute for good surgical technique, and it is of little value in arresting arterial bleeds.

Fibrin glue has other uses besides haemostasis. It can seal leaks of air or fluid13 and secure anastomoses,14 and it is used in orthopaedic15 and plastic surgery.16 In all these indications the biologically interactive fibrin sealant is absorbed after it has done its job. Mixtures of fibrin glue and antibiotics are being used for local delivery of antimicrobial activity17; when applied to contaminated surgical wounds the combination may discourage the formation of adhesions.^18,19

Fibrin glue is a blood product obtained from either commercial sources or some regional blood transfusion centres. The commercial products are produced from pools of plasma, and the final products usually contain high yields of fibrinogen and, as a result, produce firm coagulums. Fibrin glue derived from individual volunteer donations may have a low concentration of fibrinogen, but newer methods for small scale production are claimed to produce fibrinogen yields and coagulum tensile strengths similar to those of the commercial products.^5,9 Until recently the thrombin used in preparations of fibrin glue was of bovine origin and caused a few serious systemic reactions including anaphylaxis and coagulopathy owing to the development of antibodies to thrombin.^5,20 The problem has been solved by the use of human thrombin.

Non-commercial fibrin glue can be prepared from either homologous or autologous plasma; the autologous source avoids any possible risk of viral transmission. Homologous fibrin glue is prepared from donations screened in the standard, rigorous way and is as safe as other tested blood products. Most viruses can be inactivated by solvent detergent treatment, but this is ineffective against some viruses such as parvovirus B1921 and hepatitis A virus.22 Fibrin glue prepared from virally inactivated plasma is being assessed for safety and efficacy.23 Another approach is to prepare fibrin glue from homologous fresh frozen plasma from donors in whom current tests for viral markers at least six months after the donation yield negative results. This simple retrospective accreditation measure excludes the theoretical possibility of the donors having been in the “window period” when they gave blood or plasma.

Despite the established value of fibrin glue for a range of surgical indications its use is still restricted to a few surgical specialties and on a named patient basis. It is widely used in most European countries. Concern about safety and unawareness of potential applications are the main factors limiting the availability and use of fibrin glue in Britain and the United States.5 Yet uncontrolled bleeding usually requires further blood transfusions with their comparable (but small) risk of transmission of disease. When all else fails to prevent a blood ooze developing into an exsanguinating haemorrhage fibrin glue may save the patient.