Heterogeneity in Storage Pool Deficiency: Studies on Granule-Bound Substances in 18 Patients Including Variants Deficient in α-Granules, Platelet Factor 4, ß-Thromboglobulin, and Platelet-Derived Growth Factor

Abstract

Patients with storage pool deficiency (SPD) have been found previously to have diminished amounts of substances that are stored in platelet-dense granules (storage pool ATP and ADP, calcium, and serotonin) and impaired platelet aggregation responses. In these studies on 18 patients with SPD, we measured, in addition to these dense granule substances, platelet factor 4 (PF4), s-thromboglobulin (sTG). heparin-neutralizing activity (HNA). fibrinogen, and platelet-derived growth factor (PDGF). In addition, we quantified the number of α-granules, dense granules, and mitochondria in their platelets. Our findings demonstrated several defects that identified subtypes of SPD. In two groups of patients (seven patients with albinism and four miscellaneous unrelated patients), we found only a deficiency of dense granules and dense granule substances (δ-SPD). In the seven other patients, we observed variable deficiencies of α-granules and of HNA. PF4, sTG, fibrinogen, and PDGF in addition to dense granule defects. We have designated aδ-SPD as the subtype in one patient who showed the greatest α-granule defects, whereas partial deficiencies of α-granules and granule-bound substances were observed in six members of two unrelated families (αpδ-SPD). The levels of three secretable acid hydrolases (s-glucuronidase, s-N-acetylglucosaminidase, and s-galactosidase) were normal in all groups of patients, including those with α-granule defects. In addition to identifying subtypes within the SPD syndrome, our findings support the view that PDGF, PF4, sJG, and fibrinogen are stored in α-granules, whereas secretable acid hydrolases are stored in other organelles. The findings in this study further suggest that SPD could be the result of several abnormalities of granule morphogenesis in the megakaryocyte.