Reproducibility of the mechanical properties of Vivostat® system patient-derived fibrin sealant
Introduction
A major criticism of conventional patient-derived fibrin sealants is the poor reproducibility of their properties and clinical performance [1]. These sealants have been prepared historically by the mixing of a fibrinogen concentrate (e.g. cryoprecitate), obtained from an individual plasma donation, and thrombin that is usually sourced from pooled human or animal plasma. Plasma fibrinogen levels vary considerably between individuals, being affected by factors including age, sex, race, body mass index, alcohol intake, and smoking status [2], [3], [4], [5], as well as certain disease states [6], [7], [8]; values of 2–6 mg/ml are typical of patients undergoing surgery. These variations in fibrinogen concentration are reflected as similar variations in concentration of fibrin sealants prepared from individual plasma donations [9], [10], [11]; poor reproducibility in physical properties is an inevitable consequence.
The Vivostat® System1 (Vivolution A/S, Denmark), a medical device for the preparation and application of patient-derived fibrin sealant, free from added thrombin, was designed to compensate for such variations in plasma fibrinogen concentration, ensuring a reproducible sealant from patient to patient [9]. The Vivostat System utilises an enzymatic reaction to concentrate patient-derived fibrinogen in the form of fibrin I polymer, which is subsequently separated from the reacted serum and dissolved in a small volume of pH 4 buffer. This reaction has been optimised with respect to time, temperature and enzyme concentration such that a constant mass of fibrinogen is converted to fibrin I in a set time. This results in a degree of control of the fibrin I concentration due to the fact that as the plasma fibrinogen concentration increases, the fibrin I polymer recovery decreases. The Vivostat processor also incorporates a sensor system for further enhancement of the control of fibrin concentration [12]. This assesses fibrin mass, which is proportional to fibrin I volume, and enables automatic adjustment of the dilution level employed to obtain a consistent fibrin I concentration in the final sealant.
The mechanical properties of fibrin sealants depend not only on their fibrin concentration, but may also be influenced by other biochemical or chemical factors in the fibrin I solution [13], [14], [15]. Although the optimum mechanical properties of fibrin sealants have yet to be defined, wide variations in the physical properties of sealant from sample to sample are likely to be reflected as inconsistency in clinical performance. The present study was undertaken to evaluate the reproducibility in the fibrin concentration and mechanical (viscoelastic and tensile) properties of Vivostat sealant.
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Materials and methods
Vivostat Systems were supplied by ConvaTec Ltd, Deeside, UK. Vivostat-derived fibrin I solutions were prepared from freshly donated blood in the automated Vivostat Processor and used within 1 h. Vivostat-derived fibrin sealant gels were prepared by co-delivery of individually prepared samples of fibrin I solution with pH 10 buffer (in a 7:1 ratio) using the Vivostat Spraypen® applicator.
The fibrin I concentrations of the fibrin I solutions were measured using a method based on the selective
Fibrin concentration
The mean concentration of fibrin I solutions obtained from the processing of 41 samples was of 22.0±0.7 mg/ml (95% CI); the range was 17.8–26.5 mg/ml and the CV was 10.6%. The mean plasma fibrinogen concentration of the blood used to prepare these samples was 3.28±0.38 mg/ml (95% CI) (range 1.04–5.96 mg/ml, 37% CV). The mean fibrin volume was 4.77±0.25 ml (95% CI) (range 3.20–6.02 ml, 16% CV).
Rheometry
The viscoelastic properties of 21 fibrin gels were monitored at approximately 20 s intervals over a period of
Discussion
As well as having necessary adhesive properties, good clinical performance of fibrin sealants depends on having an appropriate balance of tensile and viscoelastic properties to provide the necessary strength and conformability for formation and maintenance of a good physical barrier when applied to tissues. Although other proteins and chemicals may influence the physical properties, many studies have demonstrated that fibrin concentration is a key factor in determining the physical and adhesive
References (26)
- et al.
Weekly and yearly rhythms in plasma fibrinogen in hospitalised male military veterans
Am J Cardiol
(1995) - et al.
Plasma clot welding of nerves. Experimental report
J Max Fac Sur
(1973) Commercial fibrinogen, autogenous plasma, whole blood and cryoprecipitate for coagulum pyelolithotomya comparative study
J Urol
(1978)- et al.
Comparative kinetics of polymerisation of fibrin sealants and influence on timing of tissue adhesion
Thromb Res
(2000) Fibrin sealant adhesive systemsa review of their chemistry, material properties and clinical applications
J Biomater Appl
(1993)- et al.
Epidemiological study on factor VII, factor VIII and fibrinogen in an industrial population1. Baseline data on the relation to age, gender, body-weight, smoking, alcohol, pill-using and menopause
Thromb Haemost
(1985) - et al.
Reference limits of plasma fibrinogen
Eur J Clin Chem Clin Biochem
(1992) - et al.
Curvilinear relations between age and haemostatic parameters in Chinese
Thromb Haemost
(1994) - et al.
Distribution and correlates of plasma fibrinogen in middle-aged womeninitial findings of the postmenopausal estrogen/progestin interventions (PEPI) study
Arterioscl Thromb Vasc Biol
(1995) - et al.
Fibrinogen in relation to personal history of prevalent hypertension, diabetes, stroke, intermittent claudication, coronary heart disease and family historythe scottish heart health study
Br Heart J
(1993)
Fibrinogen and cardiovascular disorders
Q J Med
Fibrin glue from single-donation aaautologous plasmapheresis
Transfusion
Biochemical aspects of autologous fibrin glue derived from ammonium sulphate precipitation
Laryngoscope
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