DIFFERENCES IN PLATELET ALPHA-GRANULE RELEASE BETWEEN NORMALS AND IMMUNE THROMBOCYTOPENIC PATIENTS AND BETWEEN YOUNG AND OLD PLATELETS

The risk of serious bleeding in patients with immune thrombocytopenic purpura (ITP) appears to be less than in comparably thrombocytopenic p atients with megakaryocytic hypoplasia. It has been proposed that this difference is due to enhanced hemostatic activity of young platelets, which are increased in the circulation during ITP. We examined alpha- granule release in reticulated platelets (RP), which are thought to be the youngest circulating platelets, and in older non-reticulated plat elets (non-RP) in normal human controls and ITP patients. Normal contr ols had a mean RP of 7%, compared with 42% in ITP pa dents. The mean c oncentration of thrombin receptor agonist peptide (TRAP) causing 50% o f control RP to express CD62P (EC50) was 0.82 +/- 0.08 mu M (SEM), sig nificantly higher than the TRAP CD62P EC50 for RP in ITP, 0.57 +/- 0.0 6 uM (p = 0.04). Similarly, the TRAP EC50 for non-RP in controls, 0.84 +/- 0.09 mu M, was significantly higher than in ITP, 0.56 +/- 0.07 mu M (p = 0.03), suggesting that all platelets in ITP have an enhanced a lpha-granule threshold response to TRAP compared with controls, while RP and older platelets within each patient group have similar threshol d sensitivities to TRAP. By contrast, high-dose TRAP caused RP to expr ess twice as much mean and total CD62P as non-RP in both ITP patients and controls (p < 0.05 for both comparisons). We conclude that compare d with controls, all platelets in ITP are primed to undergo alpha-gran ule release to TRAP, while in both ITP and controls, the newly circula ting, reticulated platelets have the potential to contribute greater a mounts of CD62P surface ligand compared with older platelets (non-RP) after stimulation. Both the increased RP% and enhanced platelet respon se to agonist in ITP may contribute to maintenance of hemostasis despi te thrombocytopenia.