Biochemical and Physical Properties of a Solvent-Detergent-Treated Fibrin Glue

Abstract

A fibrin glue preparation has been obtained from pooled human plasma using a procedure which includes a solvent-detergent (SD) treatment to inactivate lipid-enveloped viruses. The SD treatment inactivated ≥5.5 log(10) of HIV in less than 45 min, and ≥5 log(10) and ≥6.5 log(10) of VSV and Sindbis virus, respectively, in less than 2 h. The product was found to contain high quantities of fibrinogen (116±2.49 g/l; n = 12), factor XIII (35±2.88 U/ml) and von Willebrand factor (23±1.9 U/ml ristocetin cofactor activity), and relatively low levels of fibronectin (5.9±0.51 g/l). Plasminogen, the precursor of plasmin, which may play a negative role by decreasing the resistance of the fibrin clot, was at only 0.03 g/l. Cellulose acetate electrophoresis showed 95% gamma-proteins and 5% alpha-2-beta proteins. Sodium dodecyl sulfate polyacrylamide gel electrophoresis under reducing conditions detected three main protein bands with apparent molecular weights of 65, 56 and 47 kilodaltons, probably corresponding to the alpha, beta, and gamma fibrinogen subunits. Other characteristics of the product included (1) high clottability of fibrinogen (over 85%); (2) absence of low molecular weight fibrin degradation products; (3) rapid solubilization at room temperature (less than 10 min); (4) high tensile strength (202±27 g/cm^2 after 2 h of application), and (5) high elasticity of the fibrin clot. In addition, scanning electron microscopy revealed a highly organized structure showing tridimensional arrangement of the fibrin fibers. SD treated fibrin glue should efficiently replace autologous fibrinogen or cryoprecipitate preparations for surgical application.

A new surgical approach to subcortical lesions: balloon inflation and cortical gluing

“…al.,~5 demonstrated that this * Biocol distributed by Biotransfusion, ViHebon sur Yvette, France. technique minimized the neurological deficits related to this type of operation.…”

Transfusion Medicine

“…[115] These agents can be applied directly to wounds that display diffuse microvascular bleeding or can be used to seal vascular grafts. [120] Reports of two patients who underwent cardiac surgery, each of whom had been previously exposed to bovine thrombin, and subsequently presented with acquired thrombin or factor V inhibitors [121] cause concern over the potential toxicities associated with the use of either allogeneic or autologous fibrin sealants. Alternatively, the source of fibrinogen and factor XIII can be derived from as little as 40ml of the patient's autologous blood.…”

HPLC fingerprinting approach for raw material assessment and unit operation tracking for IVIG production from Cohn I+II+III fraction

“…Collected human plasma may be used as a therapeutic product or as a source for the production of pharmaceutical fractionated products [2,3]. IgG (in a form of intravenous immunoglobulin or IVIG), together with albumin and blood clotting factor VIII (FVIII) are the leading products obtained by fractionation of human plasma [2][3][4].…”

“…Classical manufacturing processes of IVIG, but also new strategies for purification are being implemented with respect to increased practicability and yield [6][7][8][9]. Simultaneously, an increasing demand for improved plasma-derived products, initiated by WHO already in 1982, has been pushing the safety levels higher and higher to reduce the risk of pathogen and viral transmissions and to limit the risk of adverse reactions proven to be linked in the presence of protein (e.g., IgA), biological/microbial (e.g., endotoxins) and chemical impurities (e.g., residual viral inactivation reagents) [4,[10][11][12][13][14][15].…”