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Hospital Healthcare Europe

Fibrin sealants: cutting costs and reducing morbidity

Martin P Sintler
1 July, 2006  

Martin P Sintler
FRCS MMedSci
Specialist Registrar  General Surgery West Midlands Rotation
UK

Rajiv K Vohra
FRCSEd FRCSEng PhD
Consultant Vascular Surgeon
Selly Oak Hospital Birmingham
UK

Materials used as local haemostats must be nonirritant, easy to handle, rapidly absorbed by the body if left in situ and have a haemostatic action independent of the general clotting mechanism. Fibrin sealants promote haemostasis, appear to have no local tissue toxicity, form a firm seal within seconds, are completely reabsorbed within days or weeks following application and work independent of the body’s coagulation cascade. They are even effective in anticoagulated patients or patients with coagulopathies. Several fibrin sealants are commercially available but vary in their specific composition, application methods, annealing times and efficacy.

Clinical use and guidelines
Blood loss is a significant risk factor in patients undergoing major surgical procedures, particularly if the loss is sufficient to require blood transfusion. Any acute fall in blood volume will be associated with an overall increase in morbidity and mortality. In some patients – for example, those undergoing neurosurgery – even small losses of blood can have devastating consequences. Even under ideal conditions, blood transfusion carries a significant risk (up to 20%) of an adverse reaction. Although these are usually mild and fully reversible others, such as acute lung injury, haemolytic reactions, infections and immunomodulation, are major risks.
 
Improving haemostasis at the surgical site can reduce blood loss and transfusion. The local application of fibrin sealants is one method that is available in addition to suturing and local pressure. The term “fibrin sealant” refers to a product containing coagulation factors. Fibrin sealants became commercially available in Europe in 1982, although the use of fibrin to facilitate haemostasis was reported for the first time in 1909 by Bergel. They are surgical haemostatic agents derived from plasma, usually human or bovine, which are designed to reproduce the final stages of the physiological clotting cascade to produce a stable fibrin clot. Bovine-derived products have the disadvantage of potential allergic reactions and the development of antibodies. Fibrin sealants have been used in patients with coagulopathies and for haemostasis, tissue sealing, tissue adhesion and drug delivery. It is important to note that there are several commercial fibrin sealants available (see Box 1). Their composition varies and therefore their efficacy in differing situations is not directly comparable.

[[HHE06_box1_T68]]

Typical fibrin sealants consist of two biological components: the biological active component (BAC), that is essentially fibrinogen, and thrombin. The two components are usually mixed at the point they are applied to the wound or tissue surface. The BAC component may contain other clotting proteins, such as fibronectin, factor XIII and von Willebrand factor, along with tranexamic acid as a stabiliser. The second component is a thrombin solution containing calcium. Thrombin is an enzyme that, in the presence of calcium, causes plasma coagulation proteins to clot. When combined, the two solutions rapidly form a clot.

Viral safety with fibrin sealants is paramount and all manufacturers are obliged to optimise viral safety. All donations are screened and potential viruses inactivated in the manufacturing process. Fibrin sealants are far safer than blood transfusion and convey a lesser risk.

The human body has its own efficient blood coagulation system that becomes activated if blood vessels are disrupted. This produces a fibrin clot that stops bleeding and acts as a matrix to support healing. Direct pressure to the wound will also aid haemostasis. While fibrin sealants have been used in patients with deficient clotting mechanisms (eg, haemophiliacs or patients with acquired coagulopathies), most fibrin sealant usage is in patients with normal clotting mechanisms. For example:

  • If application of mechanical pressure is not possible.
  • If suturing friable tissues is difficult or the tissue surface is extensive (eg, liver surface or lung tissue).
  • If reliable haemostasis is critical and blood loss may be dangerous; for example, in neurosurgery.
  • If the patient’s own coagulation is impaired.

The European guidelines for the clinical use of fibrin sealants state that although the principle of action is uniform, fibrin sealants may be used in various disease and clinical situations. But because fibrin sealant products differ in composition and application methods there are no grounds for granting a marketing authorisation on the basis of general experience with such products. For each new product a well-designed, prospective, randomised and well-controlled clinical trial must demonstrate the safety of the product and its efficacy in controlling haemostasis.

If approval for other indications to haemostasis, such as adhesion, sealing and suture support, is needed, further data or studies will be required. These situations include neurosurgery, and sealing vascular and gastrointestinal anastomoses.

Fibrin sealants have been used increasingly in numerous clinical settings and surgical disciplines including general, plastic, vascular, orthopaedic, ENT, cardiothoracic and minimally invasive surgery. In liver surgery fibrin sealants are used for reducing blood loss and bile leakage from cut liver surfaces. This is of particular use in split-liver transplantations. The fibrin sealant stops diffuse bleeding from large surfaces and also seals open biliary radicals that are not visible during the operation. This action prevents abdominal fluid collection and reduces the volume of transfused blood.

Fibrin sealants have been used in other organ surgery; for example, for reducing blood loss in splenic trauma and retroperitoneal bleeding. They have been used to stop bleeding from the lung and also to seal small bronchioles and prevent air leaks.

In radical and conservative neck surgery, they have been used to achieve haemostasis and also to reduce postoperative wound secretions. They have been used in inguinal and incisional hernia repair to reduce bleeding and seroma formation. In hip and knee surgery, which are associated with high-volume blood loss, fibrin sealants have been shown to reduce intraoperative and postoperative blood loss.

Plastic surgeons have used fibrin sealants to reduce blood loss in burns patients, to seal skin donor sites and to reduce bleeding and seroma formation under skin flaps from facelifts and reconstructive surgery. In vascular and cardiothoracic surgery they have been used to seal suture lines and support sutures and also to seal suture hole bleeding in vascular grafts.

Author viewpoint
Fibrin sealants are a useful adjuvant to traditional surgical haemostatic methods. When used correctly they can significantly reduce blood loss and cut the time needed to achieve haemostasis. In a randomised clinical trial in vascular surgery, we have demonstrated that the time to achieve haemostasis was significantly lower in the fibrin sealant group (median 2.5min, range 1–4min) as compared with the controls (median 17min, range 7–59min) p<0.001. Blood loss was also significantly reduced, median 24.5ml (range 5.5–105ml) versus 203ml (range 54.5–817ml) p<0.001. Bleeding affects not only the patient but also operating time and theatre usage.

Sealants can be drip or spray applied, with different results from each method. One must be careful not to disturb the sealant after application; movement may weaken the bond between sealant and tissue. Finally, different fibrin sealant products are not directly comparable in terms of annealing times or efficacy, and the user should be aware of this when choosing a product to use.

Conclusion
As each year passes, there are reports of new ways of using fibrin sealants for the benefit of patients. It is however becoming apparent that due to reduced bleeding and seroma formation, the patient’s intraoperative and postoperative hospital stay can be reduced along with potential complications and return visits. This in turn can save costs for the hospital. The goals of cutting costs and reducing morbidity appear to be driving the use of fibrin sealants.

Resource
European Medicines Agency, guidelines for the clinical use and investigation of fibrin sealants: W:www.emea.eu.int/ pdfs/human/bpwg/015300en.pdf