A new variant of thrombasthenia with abnormally glycosylated GP IIb/IIIa.
A 15 year-aged Japanese girl with a life long mild purpura was found as a variant type of thrombasthenia. Basic tests revealed prolonged bleeding time, border-line clot retraction, no coagulation defect, no giant platelets and mild thrombocytopenia (70,000-110,000/microliters). Neither ADP, epinephrine nor collagen aggregated her platelet rich plasma. Thrombin (0.1U/ml) caused slightly decreased aggregation of her washed platelets and about 20% normal production of thromboxane B2. PAS-stained SDS-PAGE of her whole platelets showed markedly decreased GP IIb and IIIa. However, crossed immunoelectrophoresis (CIE) against anti-whole platelets antibody showed a normal amount of GP IIb/IIIa complex in her whole platelets solubilized with 1% Triton X-100. CIE using monospecific anti-GP IIb/IIIa complex antibody showed normal dissociation of the patient's GP IIb/IIIa complex into two new bands in the presence of EDTA. Crossed affino-immunoelectrophoresis with the first dimension containing Concanavalin A revealed that the patient's GP IIb/IIIa was much less shifted to the cathode than controls. Immunoprecipitation lines of her GP IIb/IIIa complex were excised from unstained CIE using anti-GP IIb/IIIa antibody and subjected to the silver-stained reduced SDS-PAGE, which showed two protein bands with molecular weights of 125KD and 108KD, corresponding to GP IIb alpha and GP IIIa, respectively. These results suggest that the platelets of this apparently thrombasthenic patient have an antigenically normal but abnormally glycosylated GP IIb/IIIa complex, which is functionally abnormal because of abnormal glycosylation.
D000293:Adolescent; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006031:Glycosylation; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D010980:Platelet Membrane Glycoproteins / Q000032:analysis*; D011233:Precipitin Tests; D013915:Thrombasthenia / Q000097:blood*; D013917:Thrombin / Q000494:pharmacology; D013929:Thromboxane B2 / Q000096:biosynthesis
D010980:Platelet Membrane Glycoproteins; D013929:Thromboxane B2; D013917:Thrombin