title: Platelet granule disorders.
abstract: The present review has cataloged the inherited and acquired disorders of platelet granules. Unfortunately, a mere listing of different conditions in which dense bodies, alpha granules, or both are decreased, absent, or fused does little to define their importance in human platelet physiology or as a causative factor in hemorrhagic disease. The inherited disorders serve as the best index of granule involvement in platelet hemostatic function. Our experience with storage pool deficiency in patients with Hermansky-Pudlak syndrome has suggested that in many individuals virtual absence of dense bodies and their contents does not present a serious threat to hemostasis. Placing HPS patients on aspirin did not cause spontaneous hemorrhage, suggesting that secretion of dense body contents and synthesis of endoperoxides and thromboxane A2 are not absolutely essential for platelet function. However, the literature strongly suggests that many patients with HPS and SPD face a serious risk from bleeding, and hemorrhage may cause death. We can only conclude that some patients with HPS have platelet defects or other hemostatic problems that render SPD a far more serious threat than in other patients who appear to have the same disease. Dense bodies of and by themselves do not appear absolutely required for platelet function. Isolated deficiency of alpha granules presents the same enigma. Only a few patients with this rare inherited disease have been reported. They are generally considered to have mild to severe hemorrhagic problems. However, the past medical history of our two patients with GPS has recently been reviewed and platelet function studies repeated. Despite the mild thrombocytopenia, they are free of any significant bleeding episodes and their platelet function appears virtually normal. Our findings do not support the concept that alpha granules are essential for platelet function. The only condition that seems to support a critical role for storage organelles in hemostasis is the combined alpha-granule, dense body deficiency in one patient reported by Weiss. This patient does have bleeding problems. However, it is difficult to draw conclusions based on a single patient, and the discovery of other patients will help to clarify the hemostatic problem of patients with dual storage organelle deficiencies. In the meantime, we have prepared platelets from normal individuals free of storage granules by sedimentation through gradients containing cytochalasin B. The function of the normal agranular platelets is compromised, but they do respond to some aggregating agents.(ABSTRACT TRUNCATED AT 400 WORDS)
mesh_terms: D001791:Blood Platelet Disorders / Q000503:physiopathology*; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D002609:Chediak-Higashi Syndrome / Q000473:pathology / Q000503:physiopathology; D003594:Cytoplasmic Granules / Q000502:physiology / Q000648:ultrastructure; D005089:Exocytosis; D005614:Freeze Fracturing; D006801:Humans; D008854:Microscopy, Electron; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010981:Platelet Storage Pool Deficiency / Q000473:pathology / Q000503:physiopathology*; D013577:Syndrome