Further Evidence for a Deficient Storage Pool of Adenine Nucleotides in Platelets From Some Patients With Thrombocytopathia—"Storage Pool Disease"

Abstract

Abstract The metalobism of adenine nucleotides in platelets was studied in one patient with thrombasthenia and in six patients whose bleeding disorder has been attributed to a defect in collagen-induced platelet aggregation associated with impaired release of platelet ADP (thrombocytopathia). In two of these patients no specific abnormality was found that might account for the defect in the release reaction (thrombocytopathia B). In the other four patients (thrombocytopathia A), significantly decreased amounts of platelet ATP and ADP and an increase in the ATP/ADP ratio were obtained. The specific radioactivity of both ATP and, more strikingly, ADP that was found after incubating their platelets with 3H-adenine was significantly greater than normal. This indicated that the patients’ platelets lacked the nonmetabolic pool of adenine nucleotides present in specialized intracellular granules and that are specifically extruded from the platelet during the release reaction. Low platelet serotonin values were found in three of these patients, indicating that their platelets may lack the entire content of substances normally found in these granules. In all four of the patients with thrombocytopathia A, for which the name "storage pool disease" is proposed, platelet adenine uptake was normal, but increased hypoxanthine formation by resting cells was found in the three patients with low serotonin values. The breakdown of the ATP to inosine monophopshate and hypoxanthine during the release reaction was normal in all patients studied. Platelets from the patient with thrombasthenia were normal in all respects studied.