A variant of Glanzmann's thrombasthenia with abnormal glycoprotein IIb-IIIa complexes in the platelet membrane.
Patient C.M. presented platelet function defects symptomatic of Glanzmann's thrombasthenia. However, analysis of surface-labeled platelets by SDS-polyacrylamide gel electrophoresis revealed the usual presence of the major glycoproteins, including GP IIb and GP IIIa. Platelet fibrinogen was not detected. Analysis of Triton X-100 extracts of Ca2+-washed C.M. platelets by crossed immunoelectrophoresis (CIE) showed normal amounts of GP IIb-IIIa complexes. However, when samples were electrophoresed through an agarose gel containing 125I-fibrinogen, the usual binding of fibrinogen to GP IIb-IIIa did not occur. Furthermore, the GP IIb-IIIa complexes showed an increased sensitivity to dissociation with EDTA, either after Triton X-100 solubilization or in the intact platelet membrane. For example, after incubation with EDTA at room temperature, the patient's platelets bound little of the monoclonal antibodies AP-2 or T10 (anti-GP IIb-IIIa complex) although normally binding Tab (anti-GP IIb). Patient C.M. appears to represent a subgroup of thrombasthenia where platelets contain unstable GP IIb-IIIa complexes unable to support fibrinogen binding.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D001666:Binding Sites, Antibody; D001791:Blood Platelet Disorders / Q000097:blood*; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology*; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007123:Immunoelectrophoresis, Two-Dimensional; D010980:Platelet Membrane Glycoproteins / Q000097:blood*; D013915:Thrombasthenia / Q000097:blood*
D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen