FAILURE TO MOBILIZE INTRACELLULAR CALCIUM IN RESPONSE TO THROMBIN IN A PATIENT WITH FAMILIAL THROMBOCYTOPATHY CHARACTERIZED BY MACROTHROMBOCYTOPENIA AND ABNORMAL PLATELET MEMBRANE COMPLEXES

We report a mother and son who were found to have macrothrombocytopeni a, prolonged bleeding time, and abnormal platelet responses to thrombi n. Transmission electron microscopy performed on the son's platelets d emonstrated an unusual arrangement of membrane complexes formed by ass ociation of the open canalicular and dense tubular systems. Number and appearance of platelet alpha-granules, dense bodies, and mitochondria were normal. These platelets demonstrated normal agonist-induced Ca2 flux in response to collagen and supranormal responses to arachidonic acid but displayed no increase in intracellular free Ca2+ in response to thrombin. Platelet surface glycoproteins IIb-IIIa, Ib, and granula r membrane protein-140 measured by flourescence-activated flow cytomet ry, along with platelet content of von Willebrand factor and fibrinoge n, were normal. The von Willebrand factor binding function of GP-Ib on these platelets was also normal. We believe that this family demonstr ates a unique macrothrombocytopenia syndrome characterized by deficien t Ca2+ mobilization in response to thrombin that is not related to a d efect in GP-Ib.