Differences in Platelet Storage Pool Deficiency (SPD) of Hermansky Pudlak Syndrome (HPS) and Non-Albinos (NA)

Abstract

Recent reports of SDP platelets from patients with HPS (Albinism, accumulation of ceroid-like pigment, and mild hemorrhagic disease) and NA have suggested that the platelet defect in both conditions is identical. However, investigation of six HPS patients and three NA siblings with platelet SPD have indicated significant differences. The three NA patients were mildly thrombocytopenic while HPS patients had normal platelet counts. Levels of platelet serotonin (5 HT) were consistently lower in HPS than in NA with SPD, and approached normal concentrations in 2 of 3 NA patients. Dense bodies (DB), the organelles which contain the storage pool of serotonin and adenine nucleotides, were virtually absent in HPS platelets. SPD platelets from NA patients had significant numbers of DB which were markedly abnormal in their ultrastructure compared to normal platelet DB. Analysis of lipid peroxides and other substances reacting with thiobarbituric acid (TBA) revealed levels 5 to 10 times normal in HPS platelets while concentrations in SPD platelets from NA patients were similar to control values. Although the bleeding problems, aggregation defects, and abnormal platelet adenine nucleotide profiles were similar in HPS and NA patients, results of this study suggest that basic differences exist. The bizarre appearance of dense bodies in NA platelets is compatible with a structural abnormality interfering with storage organelle formation while accumulation of TBA reactive substances by HPS platelets may be the critical factor preventing development of the storage pool.