Hereditary defect in the platelet release reaction caused by a deficiency in the storage pool of platelet adenine nucleotides.

Abstract

Summary A large family has recently been described in which impaired platelet aggregation was attributed to defective release of the ADP present, although in decreased amounts, in their platelets (Weiss et al, 1969). It was postulated that these patients might lack the storage, or non‐metabolic, pool of ADP which is selectively released from specialized granules during the platelet release reaction and studies on three affected members of this family were undertaken to test this hypothesis. Citrated platelet‐rich plasma (PRP) was incubated with [8‐14C]adenine for 2 hr at 37°C and the specific activity of platelet nucleotides was determined. The release reaction was then induced by shaking the PRP with collagen fibres. The labelling patterns in the patients' platelets were distinctly abnormal. The specific activities of their platelet ADP following incubation with [14C]adenine were 4–6 times those of similarly treated normal platelets and were similar to those obtained in the normal platelets after they had been depleted of their non‐metabolic (unlabelled) ADP by treatment with collagen. The findings are consistent with the hypothesis that the patients' platelets contain a normal amount of metabolically active ADP, but are deficient in the storage pool. Similar conclusions were reached for ATP. Incubation of the patients' platelets with collagen was accompanied by a normal disappearance of radioactive ATP and accumulation of radioactive IMP and hypoxanthine. Thus the abnormality in the platelet release reaction in these patients appears to be the result of a diminished storage pool of nucleotides rather than a block in the pathway which may provide the energy for this reaction.