Storage Pool Platelet Disease

Platelet storage pool deficiencies (SPD) comprise a range of disorders encompassing variable degrees of reduction in the numbers and contents of dense granules (delta-granules), alpha-granules, or both (Weiss et al., 1979). In addition to the more frequently occurring disorders of dense granules only (delta-SPD), 2 disorders involving alpha-granule deficiencies have been characterized: alpha/delta-SPD, which includes patients with marked deficiencies of dense granules as well as more variable deficiencies of alpha-granules; and alpha-SPD, or the gray platelet syndrome (139090), in which severe reductions occur only in the alpha-granules and their contents. Both disorders are associated with impaired platelet function as indicated by decreased aggregation responses.

Weiss et al. (1969) described a kindred in which 10 members in 4 generations had a bleeding diathesis. There were several instances of male-to-male transmission. Six of the affected members were studied and found to have impaired release of platelet adenosine diphosphate (ADP). The platelets were smaller than normal. The major symptom was easy bruising. Ingestion of aspirin interferes with release of ADP even though the storage pool is normal. In a later paper on the same family, Holmsen and Weiss (1970) postulated that these patients lack the storage, or nonmetabolic, pool of ADP. Because of reduced release of ADP, collagen-induced platelet aggregation was impaired. By electron microscopy, Weiss and Ames (1973) showed a marked decrease in platelet dense bodies. Since both serotonin and the storage pool of adenine nucleotides are deficient in these platelets, the dense bodies may normally store them. Willis and Weiss (1973) showed that prostaglandin production is impaired in this disorder. In studies of 18 patients, Weiss et al. (1979) identified several defects, indicating heterogeneity. In 7 patients with albinism (Hermansky-Pudlak syndrome; 203300) and in 4 other unrelated patients, they found a deficiency of dense granules and dense granule substances. They termed this delta-SPD. In 7 other patients, they observed variable deficiencies of alpha-granules and of heparin-neutralized activity (HNA), platelet factor 4 (PF4), beta-thromboglobulin, fibrinogen, and platelet-derived growth factor (PDGF) in addition to dense granule defects. The disorder in one of these with the greatest alpha-granule defects was designated as alpha-delta-SPD. The partial deficiency in alpha granules and granule-bound substances, observed in 6 members of 2 unrelated families, was designated alpha(P)-delta-SPD. The two types of granules are observed by electron microscopy: the more numerous alpha-granules of variable electron density and the less numerous, smaller granules of highest electron density. Delta-storage pool disease appears to be an autosomal recessive (see 203300). The 2 families with alpha(P)-delta-SPD had, in one, affected mother and 2 children and in the second (Iranian in extraction) affected father and daughter and son. In the first family, the platelets of the affected persons showed also a unique lipid defect and increased amounts of glycoprotein IV. Secretable acid hydrolases were normal in all these patients, a finding consistent with their storage in lambda granules (lysosomes). The fact that in delta-SPD with normal alpha-granules, HNA, PF4, beta-thromboglobulin, fibrinogen, and PDGF were normal supports the conclusion that these substances are stored in the alpha-granules. Dense granules store serotonin, calcium, pyrophosphate, ATP, and ADP. Weiss et al. (1980) pointed out that storage pool deficiency can be an acquired disorder. The proband in the family reported by Caen et al. (1968) died of primary pulmonary hypertension (178600). Herve et al. (1990) suggested that the pulmonary hypertension was a consequence of the inherited platelet storage deficiency associated with a high level of 5-hydroxytryptamine (5-HT) in plasma. Administration of ketanserin, a 5-HT antagonist, substantially reduced pulmonary hypertension. The proband had had episodes of excessive bleeding since infancy. Lages et al. (1991) demonstrated heterogeneity in SPD patients. Some with severe alpha/delta-SPD had only about half normal amounts of the alpha-granule membrane protein GMP-140 (173610) while others had normal GMP-140 content, as measured immunologically. Rosa et al. (1987) found that both the content and the surface expression of GMP-140 were similar to that in normal platelets in 2 patients with alpha-SPD.