Autoimmune thrombocytopenic purpura (AITP) and acquired thrombasthenia due to autoantibodies to GP IIb–IIIa in a patient with an unusual platelet membrane glycoprotein composition

• Published in: American journal of hematology 1998-02, Vol.57 (2), p.164-175
• Main Authors: Macchi, Laurent, Nurden, Paquita, Marit, Gérald, Bihour, Claude, Clofent‐Sanchez, Gisèle, Combrié, Robert, Nurden, Alan T.
• Format: Article
• Language: English
• Subjects: autoantibodies; Autoantibodies - blood; Autoantibodies - immunology; autoimmune thrombocytopenic purpura; Autoimmunity; Biological and medical sciences; Blood Platelets - metabolism; Blood Platelets - ultrastructure; Female; GP IIb–IIIa complexes; Hematologic and hematopoietic diseases; Humans; Medical sciences; Middle Aged; Platelet diseases and coagulopathies; Platelet Glycoprotein GPIIb-IIIa Complex - immunology; Platelet Membrane Glycoproteins - immunology; Platelet Membrane Glycoproteins - metabolism; platelets; Purpura, Thrombocytopenic - blood; Purpura, Thrombocytopenic - complications; Purpura, Thrombocytopenic - immunology; Thrombasthenia - blood; Thrombasthenia - complications; Thrombasthenia - immunology
• ISSN: 0361-8609; 1096-8652
• DOI: 10.1002/(SICI)1096-8652(199802)57:2<164::AID-AJH13>3.0.CO;2-C

The subject (E.B.) is a 63‐year‐old woman with autoimmune thrombocytopenic purpura (AITP) who was first examined some 6 years ago with symptoms of epistaxis and gum bleeding, severe thrombocytopenia, and large platelets. Her serum tested positively with control platelets in the MAIPA assay performed using monoclonal antibodies (MoAb) to glycoprotein (GP) IIIa (XIIF9, Y2/51), yet was negative in the presence of MoAbs to GP IIb (SZ 22) or to the GP IIb‐IIIa complex (AP2, P2). The patient's platelets failed to aggregate with all agonists tested except for ristocetin. IgG isolated from the patient's serum inhibited ADP‐induced aggregation of control platelets. Unexpectedly, flow cytometry showed an altered expression of membrane glycoproteins on the patient's platelets. Levels of GP Ib‐IX were much higher than previously located by us in platelets. In contrast, the expression of GP IIb‐IIIa was about half that seen with control subjects. When Western blotting was performed, a striking finding was a strong band of 250 kDa recognized by a series of MoAbs to GP Ibα in addition to the band in the normal position of GP Ibα. Finally, ADP‐stimulated (E.B.) platelets failed to express activation‐dependent epitopes on GP IIb‐IIIa as recognized by PAC‐1, AP6, or F26 and additionally gave a reduced P‐selectin expression after thrombin addition. In conclusion, we present a novel patient with a severely perturbed platelet function where an altered membrane GP profile is associated with the presence of an autoantibody recognizing a complex‐dependent determinant on GP IIb–IIIa and inhibitory of platelet aggregation. Am. J. Hematol. 57:164–175, 1998. © 1998 Wiley‐Liss, Inc.