Analysis of platelet aggregation using particle collision theory

Abstract

The aggregometer monitors changes in light transmission through stirred suspensions of aggregation platelets. Arbitrary measurements from aggregometer recorder tracings have been used to investigate platelet aggregation without regard to mechanisms involved. To determine the applicability of particle collision theory to assessment of in vitro platelet sensitivity to proaggregating agents, platelet-rich plasma (PRP) from five volunteers was used to obtain recorder tracings after addition of ADP in five doses (0.4-4.0 mumol/l PRP) to aliquots of PRP stirred and incubated in an aggregometer. Using the equation describing light transmission through particulate suspensions, particle collision theory, and s (the probability of particle union after collision), a subject- and dose-independent relationship between aggregation rate (dn/dt) and particle number (n) at the recorder tracing inflection point was found (dn/dt = -k X s X n1.56, where k is a constant dependent on particle size and speed and on the proportion of unreactive particles). Determinations of mean particle size at the tracing inflection point indicated that k was also dose independent. Dose-response curves of ADP added vs. s could therefore be constructed. This methodology provides conveniently obtainable quantitative information concerning in vitro platelet "stickiness."

Platelet sensitivity in vitro to adenosine-5?-diphosphate and prostacyclin and diabetic retinopathy

“…The subjects attended fasting and in random order. Blood was taken for use in aggregation studies [8], for estimation of plasma glucose (glucose oxidase, Boehringer GOD-Perid kit, Lewes, UK), and for determination of glycosylated haemoglobin [9]. Results given as median with ranges in parentheses Aggregation studies for each subject were performed as described by Davis and Bown [8] using platelet-rich plasma with a standard count of 250,000/ml.…”

“…Blood was taken for use in aggregation studies [8], for estimation of plasma glucose (glucose oxidase, Boehringer GOD-Perid kit, Lewes, UK), and for determination of glycosylated haemoglobin [9]. Results given as median with ranges in parentheses Aggregation studies for each subject were performed as described by Davis and Bown [8] using platelet-rich plasma with a standard count of 250,000/ml. A conventional aggregometer (Payton Associates, Buffalo, Illinois, USA) provided the data required for collision theory analysis: a platelet dilution curve (the forms of which were similar for both diabetic and non-diabetic subjects) and aggregation tracings for ten final ADP concentrations ranging from 0.2 to 4.0 am 9…”

“…These doses provoked a range of aggregation for minimal to irreversible in all subjects. The collision theory model was used to calculate a 'sticking probability' (the probability of particle union following collision) for each ADP dose at the point of maximal first-phase aggregation [8]. The model is based on a constant relationship between the collision rate and number of particles present in the aggregometer curette.…”

“…The results of most of the studies concerned with platelet aggregation in diabetes mellitus suggest that platelets from diabetic subjects are hypersensitive to pro-aggregating agents in vitro [1,2]. Prostacyclin is thought to counter the pro-aggregatory behaviour of platelets in vivo [3], and, although decreased vascular prostacyclin production might not, as first postulated [4], occur in diabetes [5], platelet prostacyclin sensitivity may be depressed [6, 71. In the present study, the sensitivity of platelets from normal subjects and from matched diabetic patients both with and without retinopathy to a range of doses of adenosine diphosphate (ADP) and prostacyclin was investigated using a model of platelet aggregation based on particle collision theory [8]. This model allows interpretation of platelet sensitivity to ADP and prostacyclin in terms of 'sticking probability', a measure which reflects the haemostatic function of platelets.…”

High-speed platelet adhesion under conditions of rapid flow.

“…2A platelet concentration (6,37). This distinction in the dependence of adhesion rate versus platelet number, compared to aggregation, strongly suggests that aggregation was not occurring.…”