TRANSIENT AGGREGATION RESISTANCE OF HUMAN PLATELET-RICH PLASMA; A NEGLECTED IN VITRO PHENOMENON WITH PHYSIOLOGICAL IMPACT
Due to instability in the first in vitro period, platelet-aggregometry is usually deliberately postponed until ca. 1 hour after venepuncture (VP) . At that time aggregability is fairly constant for 1 hour or more. Investigation of the period immediately followed VP, hcwever, revealed a high aggregation resistance - measured as the threshold ADP-concentration which the platelets just could resist before they aggregate maximally and irreversibly - which subsequently decreased exponentially with
... xponentially with time. This "Transient Aggregation Resistance" (TAR) appeared to be superimposed on a stable, so called Baseline Aggregation Resistance (BAR) .The latter, measurable 60 min or more after VP, yields the "classical" threshold ADP-concentration.Parallel aggregation-studies started 6 min after VP, subsequent studies were performed every 4 min. pH was controlled during storage of PRP at rocmtenperature. Extrapolation of the TAR-curve to t=0 (i.e. time of VP) yields the maximal value:TARmax Coefficients of variation for TARmax-method: 9.4% (n=6) ; intraindividial 15% (n=15, over 3 yrs); interindividual: 51% (n=16,wide range).This TAR-phencmenon which is proven to be caused by a plasma-factor, can be influenced by dietary n-3 fattty acids and can be also inhibited by ASA,suggesting a prostanoid nature. The physiological significance of TAIfoax can be illustrated by the following findings:1. Patients with myocardial infarction, hyperlipoproteinemia, sickle cell anemia (i.e. diseases with a high risk for thrombotic complications) have low TARmax-values. 2.Individuals with "spontaneous platelet aggregation" in vitro,but asymptomatic, have positive TARmax-values. 3.There is a clear,reciproke age-dependency of TARmax It is concluded that a technique is available measuring the effect of circulating,labile platelet-aggregation influencing plasma factor(s). Furthermore, using this technique,it was found that normal fresh plasma contains a labile aggregation-inhibiting factor which is several orders of magnitude more potent than other stabile factors either present in plasma or associated with platelets. This factor is probably of prostanoid nature and might have significance as a reflection of the antithrcmbotic potential of the endothelium.