Antithrombotic Prophylaxis Through Modification of Fibrin Network Structure:a New Approach.

Abstract

Morphometric analysis of electron micrographs have demonstrated that diameters of fibrin strands follow a bimodal distribution comprising a major network of thicker fibres with a minor network interspersed and made up of very fine fibres. The relationship between the two networks is not fixed and invariant. It will be shown that the two networks are highly responsive to changes in the physiological conditions of clotting. Such a system has biological adaptability and tends to result in fibrin which is more suited to serve its varying roles in haemostasis, in limiting sepsis, in promoting neovascularization and in acting as a scaffolding for wound repair.The response of the two network system to dextran, an agent widely used and well known for its antithrombotic properties, has been examined. It will be shown that in vitro dextran increases fibrin fibre thickness, reduces permeability and tensile strength of networks developed in plasma. Similar changes were found to follow when dextran is infused in clinical dosage in man. It was found that the increase in the thickness of major network fibre is at the expense of protein in the minor network. Such means of modulating distribution of fibrin fibre diameter within fibrin networks provide a new approach to antithrombotic prophylaxis.