Dose-dependent increase in in vitro platelet sensitivity to adenosine-5'-diphosphate in young complication-free...

In vitro platelet aggregation in response to a wide range of final adenosine-5'-diphosphate (ADP) concentrations was assessed in 11 young, diabetic males without detectable vascular complications and in 11 closely-matched controls. First phase aggregation was assessed using a particle collision theory model and the "sigmoid Emax" dose-response equation. Platelets from the diabetics required a significantly lower ADP concentration to attain a sticking probability of 0.2 (EC20; median [95% confidence limits]; 0.38 mumol/l ADP [0.25-0.52]) than those from the controls (0.55 mumol/l [0.28-0.67]; p = 0.016). At higher concentrations (EC50, EC80), there were no significant differences between the two groups (p greater than 0.05). Second phase aggregation, assessed from threshold for initiation of the release reaction, occurred at lower ADP concentrations in the diabetic group (2.0 mumol/l [1.2-4.4] vs 3.2 mumol/l [1.6-7.0]; p = 0.009). Consistent with the multistep nature of ADP-induced aggregation, these results indicate dose-dependent platelet function abnormalities in diabetics without vasculopathy. Enhanced reversible microaggregate formation (associated with platelet shape change) at low ADP concentrations may precede other first phase changes in early diabetes and would explain apparent inconsistencies in the results of previous studies involving similar subject groups.