Disease relevance of Platelet Storage Pool Deficiency

• Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies [1].
• Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb-IIIa (thrombasthenia), or granule substances (storage pool deficiency, SPD) were studied to define further the properties of platelets that mediate platelet adhesion and thrombus formation on subendothelium [2].
• A storage pool deficiency of adenine nucleotides was considered to be responsible for abnormal platelet function in patients with myeloproliferative disorders [3].
• The rare autosomal recessive metabolic disorders Hermanky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS)share the clinical findings of oculocutaneous albinism and a platelet storage pool deficiency [4].
• In the rat, only two HPS models are known, Fawn-hooded (FH) and Tester Moriyama (TM), non-complementing strains in which HPS-like hypopigmentation and platelet storage pool deficiency result from a mutation of the Ruby (red eyed dilution; R) locus on Chromosome (Chr) 1 [5].

High impact information on Platelet Storage Pool Deficiency

• The pallid gene encodes a novel, syntaxin 13-interacting protein involved in platelet storage pool deficiency [6].
• Decreased content and surface expression of alpha-granule membrane protein GMP-140 in one of two types of platelet alpha delta storage pool deficiency [7].
• Platelet prothrombinase activity and intracellular calcium responses in patients with storage pool deficiency, glycoprotein IIb-IIIa deficiency, or impaired platelet coagulant activity--a comparison with Scott syndrome [8].
• Other platelet abnormalities include a mild storage pool deficiency and abnormal expression of two low-molecular-weight guanosine triphosphate binding proteins [9].
• Quantification of a novel dense granule protein (granulophysin) in platelets of patients with dense granule storage pool deficiency [10].

Chemical compound and disease context of Platelet Storage Pool Deficiency

• Our findings suggest a new platelet disorder with impaired secretion mechanism, without storage pool deficiency or impaired arachidonate metabolism [11].
• Aggregation responses and thromboxane (Tx) formation in ten patients with storage pool deficiency (SPD) specific to the dense granules (delta-SPD) were studied to assess further the role of dense granule adenosine diphosphate (ADP) in mediating platelet aggregation by epinephrine [12].
• We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD) [13].
• The secretion of the dense granule constituents ATP, ADP, calcium, pyrophosphate (PPi), and orthophosphate (Pi), and the release of magnesium induced by thrombin and the divalent cation ionophore A23187 have been quantitated directly in gel-filtered platelets from patients with storage pool deficiency (SPD) [14].
• Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency [13].

Biological context of Platelet Storage Pool Deficiency

• Pallid (pa) is 1 of 13 platelet storage pool deficiency (SPD) mouse mutants. pa animals suffer from prolonged bleeding time, pigment dilution, kidney lysosomal enzyme elevation, serum alpha1-antitrypsin activity deficiency and abnormal otolith formation [6].
• Two human platelet storage pool deficiencies (SPD), Hermansky-Pudlak syndrome and Chediak-Higashi syndrome, are recessively inherited and characterized by hypopigmentation, prolonged bleeding, and normal platelet numbers accompanied by a reduction of platelet dense granules [15].
• The recessive muted (mu) and pearl (pe) mutations on Chromosome (Chr) 13 cause pigment dilution and platelet storage pool deficiency (SPD) in mice [16].

Anatomical context of Platelet Storage Pool Deficiency

• For example, platelet storage pool deficiency (SPD) is due to a marked decrease or absence of the organelles storing adenine nucleotides, serotonin, and calcium destined for secretion during the platelet release reaction [17].
• Although not completely elucidated, this bleeding tendency may be associated with ineffective binding of the von Willebrand Factor (a component of factor VIII) to platelet membranes, acquired storage-pool deficiency, and anemia [18].
• Only platelets from patients with the gray platelet syndrome (GPS) and one patient with alpha delta platelet storage pool deficiency (alpha delta SPD) had more Golgi complexes in their cells than were found in normal thrombocytes [19].
• Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder causing oculocutaneous albinism and a platelet storage pool deficiency, reflecting defective biosynthesis and/or processing of melanosomes and platelet dense bodies [20].

Gene context of Platelet Storage Pool Deficiency

• Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a platelet storage pool deficiency [21].
• RUNX1 (AML1, CBFA2) is mutated in affected members of families with autosomal dominant thrombocytopenia and platelet dense granule storage pool deficiency [22].
• Mocha (mh), a mouse model for Hermansky-Pudlak syndrome (HPS), is characterized by platelet storage pool deficiency, pigment dilution, and deafness as well as neurological abnormalities [23].
• Heterogeneity in storage pool deficiency: studies on granule-bound substances in 18 patients including variants deficient in alpha-granules, platelet factor 4, beta-thromboglobulin, and platelet-derived growth factor [24].
• These results suggest that defective aggregation in SLE platelets may be partially related to a storage pool deficiency state [25].

References