A molecular defect in thrombasthenic platelets.

An IgG antibody found in the serum of a thrombasthenic patient reacted in complement fixation with platelets from 350 normal individuals but was nonreactive with platelets from eight other thrombasthenic patients. ADP-induced aggregation of normal platelets was inhibited by the patient's antibody. Family studies using the quantitative complement fixation test showed that healthy heterozygotes were easily distinguishable from normal or thrombasthenic individuals since their platelets had an intermediate amount of the reactive antigen. Indirect immunoprecipitation tests using this serum and soluble membrane antigens labeled with iodine-125 that had been extracted from normal platelets by the detergent Nonidet P-40 gave a single radioactive peak at 120,000 mol wt in sodium dodecyl sulfate polyacrylamide gel electrophoresis. A similar estimate of the molecular weight was obtained from Sephadex G-200 filtration of the soluble antigens extracted from normal platelets by spontaneous release or chaotropic agents and tested in complement fixation with the patient's serum. These findings strongly suggest that the molecule recognized by this antibody is absent or structurally modified in thrombasthenia cases and that it may be involved in platelet aggregation.