Polymolecular layers of fibrinogen systems and the genesis of thrombosis

Abstract

In 1971 Copley proposed a new theory on the initiation of thrombosis, based on hemorheological observations. A brief summary is given of observations pertaining to the plasmatic zone in relation to the cement fibrin in the proposed endoendothelial layer as well as of earlier findings on thromboid surface layers. They concern viscous resistance (torque values, τ, dyne. cm) of layers of systems of fibrinogen and other plasma proteins. New findings are presented of viscous resistance of surface layers of fibrinogen systems, obtained in steady shear together with findings on the elastic component, secured in oscillatory shear. A new concept on maintaining the patency of microvessels, presented by Copley in 1974, is related to the problem of the initiation of thrombosis. During life, both with the patency of the vascular lumen and with intravascular obstruction, which by necessity are opposite, the stresses on the blood vessel walls are extremely high, particularly in the capillary or minute blood vessels. Fibrinogen systems were therefore exposed to high shear at 1000 sec −1 for 3 min prior to measurements. Thereafter, data were secured from 10 −3 to 10 −1 sec −1. Highly purified β lipo-protein and γ globulin, which gave no τ values also showed none when previously exposed to high shear. However, all hitherto tested fibrinogen preparations from different mammalian species (human, bovine, sheep, dog, rabbit, and cat) exhibited high τ values. They usually became higher if subjected to 3 min of high shearing prior to the low shear testing. The findings are related to a new hypothesis proposed by Blombäck and Copley on the transformation of the fibrinogen molecules, caused by high shearing. Such shearing forces, according to this concept, would open up the polymerization sites of fibrinogen and thus simulate the enzymatic action of thrombin for the polymerization of fibrin. The difference between the biochemical and hemorheological actions is that the fibrinopeptides are split off by thrombin, while no such cleavage would occur in fibrinogen, proposed to be altered physically by the high shear known to exist at the vessel wall. The layer upon layer deposition of such hemorheologically configurated fibrinogen and its polymerization would proceed, resulting in the formation of a thrombus which thus would initiate thrombosis and hemostasis. Copley considers blood cellular aggregation and fibrin coagulation to be secondary processes in the genesis of thrombi in minute or capillary blood vessels.