Quantification of the morphological reaction of platelets to aggregating agents and of its reversal by aggregation inhibitors.

Abstract

SUMMARY1. In rabbit citrated platelet-rich plasma, the changes in shape of the platelets produced by adenosine diphosphate (ADP) or 5-hydroxytryptamine (5-HT) were observed by photometric and volumetric techniques and by measurements of platelet images on electron micrographs either directly or with an image analysing computer. This permitted the indirect manifestations of the shape changes to be correlated with the morphological features responsible for them, i.e. transformation of disks to more spherical forms and extrusion of blebs and spikes.2. Following the addition of ADP, an initial brief peak in the light scattering records was associated with marked but transient irregularities in the surface of the platelets. These effects were absent when the other shape changes were produced by 5-HT.3. When the optical manifestations of the shape changes induced by ADP were reversed by the addition of antagonists adenosine triphosphate, 2-chloroadenosine or prostaglandin E1, the morphological changes were reversed by a diminution in the number of spikes and the conversion of spherical platelet bodies to a more discoid form.4. The volume of extracellular plasma trapped between platelets sedimented by centrifugation was proportional to the number of spikes which they extruded. Under all conditions, the volume of the platelets themselves remained remarkably constant at approximately 5 x 10-9 ,ul./platelet.5. Addition of a calcium chelating agent alone produced a rapid persistent alteration in the optical properties of platelet-rich plasma. The magnitude of this alteration was proportional to chelator concentration but greater in some plasmas than in others. Similar optical effects were produced when the calcium concentration * Present address:

Platelet Aggregation Is Not Initiated by Platelet Shape Change

“…In contrast to the results obtained with general photometers (O'Brien, 1962), an initial decrease in transmission was observed with the devices specifically designed for platelet aggregometry by Born (Born et al, 1978;Latimer et al, 1977). It was suggested that this optical effect was caused by the morphological change of platelets from discs to spherical cells with pseudopodia (Latimer et al, 1977).…”

“…The initial decrease in light transmission was first observed with devices specifically designed for platelet aggregometry by Born (Born et al, 1978;Latimer et al, 1977), in which the angle of light collection is small. Based on theoretical calculations, Latimer (1983) predicted that in a Born-type aggregometer microaggregation leads to a decrease in light transmission.…”

“…It was suggested that this optical effect was caused by the morphological change of platelets from discs to spherical cells with pseudopodia (Latimer et al, 1977). Transmission electron microscopy was used to support the interpretation that the initial decrease in light transmission was caused by platelet shape change (Born et al, 1978). Since then, the initial decrease in light transmission detected in aggregometry is used as a measure for the extent of platelet shape change.…”

Increases in Aggregation by and Uptake of 5‐hydroxytryptamine With Platelets From Rabbits Treated With Chlorpromazine

“…Even so, 5-HT produced its characteristic shape-changing effects on the platelets (Born, Dearnley, Foulks & Sharp, 1978) which was clearly demonstrable (Figure la).…”

Shape Changes Induced by Biologically Active Peptides and Nerve Growth Factor in Blood Platelets of Rabbits

“…This change can be quantified by measuring the light absorption of the platelet suspension (Born, Dearnley, Foulks & Sharp, 1978). One group of shape change-inducing agents, represented by substances like 5-hydroxytryptamine (5-HT) and adenosine 3', 5'-diphosphate (ADP), probably acts through specific receptors at the plasma membrane, as has been shown by shape change and binding studies with specific agonists and antagonists of 5-HT and ADP receptors (Born, 1970;Drummond, 1976;Adler & Handin, 1979).…”