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 platelet counts of 40 and 65 x 10(9)/L respectively as assessed by contrast phase microscopy. Ultrastructural studies revealed giant spheroid platelets with characteristic large membrane complexes and/or giant vacuoles containing platelet 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 disorder. Platelet autoantibodies were repeatedly absent. Nevertheless, in the peripheral blood we observed several figures of platelet phagocytosis by macrophages and neutrophils. The in vitro aggregometric response of platelets to ADP, collagen, thrombin, ristocetin was present, but shape change was absent. The urinary excretion of thromboxane A2 metabolites of the affected subjects were approximately 2 standard deviations above control values, in spite of a reduced maximal biosynthetic capacity of thromboxane from giant platelets assessed in vitro during whole blood clotting. This inherited platelet disorder shows structural and functional features which allow to distinguish it from other syndromes associated with giant platelets. We also propose to include ultrastructural and cytoskeletal studies in the diagnosis as well as in the classification of inherited giant platelet disorders