Estimation of platelet function inhibiting drugs on platelet adhesiveness

Abstract

The use of drugs which inhibit platelet function as potential antithrombotic agents has gained considerable support with recognition of the important role of platelet in thrombus formation. The identification of drugs that suppress platelet function and retard thrombosis in experimental models are also recognized. It is very difficult to assess correctly whether or not platelet function inhibiting drug is efficacious as antithrombotic agent. But it would be clinically required to have laboratory method for an evaluation of efficacy and dosage of the drugs.
From this point of view, studies were done to establish the criteria for an assessment of the effects to suppress platelet functions.
Method: Platelet adhesiveness was measured using Salzman-Yasunaga modified method. Platelet retention rate in a glass bead column was expressed as an adhesiveness (%). Platelet aggregation was measured by a densitometric technique and its strength was presented as a maximum aggregation rate at final concentration of ADP; 2×10^-6M, collagen; 10μg/ml and adrenalin; 9×10^-3M respectively.
Results and Discussion: Variation of adhesiveness (%) and that of ADP-, collagen- and adrenalin- induced maximum aggregation rates during the 6 month period were tested in 14 cases treated with platelet function inhibiting drugs. The coefficients of variation were 9.3% to 39.4% (mean 22.0%±SD 10.3%) in adhesiveness, 12.4 % to 55.4% (30.7±13.7) in ADP, 6.3% to 73.5% (25.3±17.6) in collagen and 12.15 to 82.8% (39.9±20.6) in adrenalin induced maximum aggregation.
The relationships between adhesiveness (%) and maximum aggregation rates induced by ADP, collagen and adrenalin were studied in 94 samples tested during 1 month period before and after the drug. The coefficients of correlation were 0.49, 0.48 and 0.48 respectively with statistically significanse.
The platelet adhesiveness (%) in normal subjects (50 males and 50 females) was determined. The mean values and standard deviations were 46.0±11.3 (%) in male, 40.7±13.6 (%) in female and 43.4±12.8 (%) in total subject respectively.
We found that Salzman-Yasunaga modified method is simple and rapid technique. This method may be a reasonable clinical screening test to detect platele tadhesiveness and showed stable data in comparison with aggregation test. Therefore, platelet adhesiveness by this method and the mean ±SD in normal subjects were set as a criteria for an asessment of platelet function inhibiting efficacy.
The efficacy of platelet function inhibiting drugs was determined as follow:
A=times of measurement which showed below 56.2 (%)/total times of measurement×100
80%≤A: good control “G”
80%>A≥50%: fair control “F”
A<50%: poor control “P”
According to this criteria, adhesiveness inhibiting efficacies of gliclazide (antidiabetic agent), dipyridamole and aspirin in vivo were assessed respectively. The gliclazide (80-240mg/day) conducted “G” in 6, “F” in 1 and “P” in 3 of 10 patients, and the dipyridamole (150-500mg/day) did “G” in 5 and “P” in 5 of 10 patients, at 3 month after these drugs. The aspirin inhibited platelet adhesiveness in all of 4 patients at 1 month after (1.0-3.0g/day). Those who showed poor control at 3 months after gliclazide and dipyridamole remained poor even after 6 to 12 months.