Inherited macrothrombocytopenia with distinctive platelet ultrastructural and functional features

We report a family with inherited macrothrombocytopenia and characteristic large membrane complexes in the platelets. Two affected subjects had platel et counts of 40 and 65x10(9)/L respectively as assessed by contrast phase m icroscopy. Ultrastructural studies revealed giant spheroid platelets with c haracteristic large membrane complexes and/or giant vacuoles containing pla telet organelles. Immunohistochemical studies of actin and tubulin showed a disorganization of the microtubule and actin systems. These abnormalities were absent in leukocytes, indicating a platelet-specific cytoskeleton diso rder. Platelet autoantibodies were repeatedly absent. Nevertheless, in the periph eral blood we observed several figures of platelet phagocytosis by macropha ges and neutrophils, The in vitro aggregometric response of platelets to AD P, collagen, thrombin, ristocetin was present, but shape change was absent. The urinary excretion of thromboxane A(2), metabolites of the affected sub jects were approximately 2 standard deviations above control values, in spi te of a reduced maximal biosynthetic capacity of thromboxane from giant pla telets assessed in vitro during whole blood clotting. This inherited platelet disorder shows structural and functional features w hich allow to distinguish it from other syndromes associated with,giant pla telets. We also propose to include ultrastructural and cytoskeletal studies in the diagnosis as well as in the classification of inherited giant plate let disorders.