Membrane defects in inherited disorders of platelet function.

Recent biochemical and ultrastructural studies have demonstrated that membrane defects are common in abnormal cells from patients with inherited hemorrhagic disorders due to platelet disfunction. Thrombasthenia is a classic example of the defect in platelet-platelet adhesion. The inability of thrombasthenic platelets to stick to one another or to sites of vascular injury appears due to a marked deficiency or absence of specific surface membrane glycoproteins. The abnormal platelets of patients with the Bernard-Soulier syndrome are capable of adhering to one another, but fail to stick to the sites of vascular injury. Defective platelet function in this disorder appears related to a marked deficiency or absence of a surface membrane glycoproteins missing in patients with thrombasthenia. The Hermansky-Pudlak syndrome is a mild bleeding disorder in which the platelets are markedly deficient in the storage pool of adenine nucleotides and serotonin. These products are normally stored in a specific type of storage organelle, the dense body. HPS platelets appear unable to form these organelles or cannot concentrate the products in them due to an organelle membrane defect. The Gray-platelet syndrome is another example of an organelle membrane abnormality. Gray platelets develop normal numbers of dense bodies and lysosomes, but appear selectively unable to form the membranes necessary to enclose alpha-granules. Giant cytoplasmic granules are the hallmark of the Chediak-Higashi syndrome. In addition to a high frequency of giant granules, platelets from most patients with this disorder are deficient in the storage pool of adenine nucleotides and serotonin and the dense bodies in which these products are contained. Thus, membrane defects of various types are common in inherited disorders of platelet function and should also be looked for in all patients with acquired platelet defects.