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 macrothrombocytopenia, prolonged bleeding time, and abnormal platelet responses to thrombin. Transmission electron microscopy performed on the son's platelets demonstrated an unusual arrangement of membrane complexes formed by association 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 granular membrane protein-140 measured by fluorescence-activated flow cytometry, along with platelet content of von Willebrand factor and fibrinogen, were normal. The von Willebrand factor binding function of GP-Ib on these platelets was also normal. We believe that this family demonstrates a unique macrothrombocytopenia syndrome characterized by deficient Ca2+ mobilization in response to thrombin that is not related to a defect in GP-Ib.