Treatment of difficult-to-heal venous ulcers with fibrin sealant

By Luciana P. F. Abbade, Associate professor, Department of Infectology, Dermatology, Imaging Diagnosis and Radiotherapy, Botucatu Medical School (FMB) and Benedito Barraviera, Full professor, Center for the Study of Venoms and Venomous Animals (CEVAP), São Paulo State University (UNESP), Botucatu, SP, Brazil

Venous diseases of the lower limbers as varicose veins or after deep vein thrombosis are the main causes of chronic and difficult-to-heal ulcers. These ulcers affect an adult population and represent a serious public health problem due to their high prevalence, long time required for healing, frequent recurrences, and high treatment costs, ultimately affecting the patient’s quality of life. Local treatment is essential to promote the wound bed preparation to accelerate the healing process. In this context, the fibrin sealant, composed of fibrinogen and thrombin, appears as an alternative treatment. In the presence of calcium chloride and factor XIII, thrombin converts fibrinogen into insoluble fibrin, forming a stable network. Besides its important role in hemostasis, fibrin together with the matrix of protein acts in the healing process to promote angiogenesis, collagen synthesis, as well as wound contraction and reepithelization.

Several clinical studies reported the benefits of using fibrin sealant to treat chronic ulcers. Besides its adherence function, this product is an excellent biological scaffold. Its characteristic of adhering to the ulcer bed for at least four days makes it an excellent drug delivery system releasing cells and growth factors. The review published in the Journal of Venomous Animals and Toxins including Tropical Diseases (vol. 26) entitled “Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies” explores how fibrin sealant is used in several clinical situations promoting healing of different ulcer types, especially venous ones and those that do not respond to conventional treatment. In most studies, autologous (obtained from the individual’s own cryoprecipitate) or homologous (obtained from a pool of human donors) fibrin sealants were used for fixation of grafts or as a scaffold for incorporation cells, especially keratinocytes. Ulcers showed an improvement, with healing or reduction of their areas in most patients who used this therapy.

Image: Abbade et al., 2020.

Figure 1. (A) After 2 to 5 minutes of application of the product on wound bed, fibrin polymerization occurs with colorless gel characteristics. (B) Gauze soaked in essential fatty acids, in a quantity sufficient to cover the entire ulcerated surface. (C) Application of Unna’s boot dorsally from the foot up to just below the knee

Despite all the precautions taken by manufacturers in the production of commercial sealants that utilize human plasma pool, the risk of transmission of new or even old viruses, is still present. Also, the high costs of these sealants make their routine use unfeasible. To circumvent such problems, the Center for the Study of Venoms and Venomous Animals (CEVAP) of São Paulo State University (UNESP), Brazil, has been researching and developing a new fibrin sealant since the 1990s. The heterologous fibrin sealant (recently known as fibrin biopolymer) has been standardized using two biological components: fibrinogen extracted from the blood of buffaloes Bubalus bubalis and an enzyme obtained from the venom of South American rattlesnake Crotalus durissus terrificus.

This review showed the difficulty faced by health professionals who treat chronic ulcers using commercial fibrin sealants especially due to their high costs. The heterologous fibrin sealant – the only one produced, developed, and studied worldwide to date – is not yet commercial, but it is easy to handle and has a low production cost due to raw material abundance. The two clinical trials carried out by our research group showed the safety and promise efficacy of this new biopolymer.

To read the article, access it

ABBADE, L.P.F., et al. Chronic venous ulcers: a review on treatment with fibrin sealant and prognostic advances using proteomic strategies. J. Venom. Anim. Toxins incl. Trop. Dis [online]. 2020, vol. 26, e20190101, ISSN: 1678-9199 [viewed 14 September 2020]. DOI: 10.1590/1678-9199-JVATITD-2019-0101. Available from: http://ref.scielo.org/d8jwvz

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