Background: The notable discrepancy between platelet count and bleeding manifestations in immune thrombocytopenia (ITP) patients with acquired Glanzmann thrombasthenia (GT) has been described.
Objectives: We aimed to examine the mechanisms responsible for thrombocytopenia and the bleeding phenotype in a patient with acquired GT.
Patient, methods, and results: A patient with primary ITP underwent splenectomy due to steroid intolerance. Despite platelet count normalization, bleeding continued. Platelet aggregometry was abnormal with all agonists except for ristocetin. Flow cytometry demonstrated the presence of antiplatelet antibody, which caused dose-dependent inhibition of fibrinogen and PAC-1 binding, induction of neuraminidase-1 expression as well as platelet desialylation in donor platelets. Indirect monoclonal antibody immobilization of platelet specific antigen assay (MAIPA) confirmed specificity to αIIb β3 only, corroborated by binding on Chinese hamster ovary (CHO) cells expressing human glycoprotein αIIb β3 but not GP Ib/IX. Both desialylation and neuraminidase expression were observed with plasma adsorbed on Ib/IX CHO cells and with the immunoglobulin G (IgG) fraction. Desialylation was inhibited in the presence of anti-Fc-gamma receptor IIa (FcγRIIa) antibody. A nonobese diabetic/severe combined immunodeficient ITP murine model was established, which showed rapid hepatic donor platelet clearance in the presence of patient IgG. Treatment of mice with the neuraminidase inhibitor oseltamivir significantly reduced antibody-induced platelet destruction.
Conclusions: We report the first case of a patient with acquired GT due to ITP with FcγRIIa mediated platelet desialylation, independent of platelet activation. Treatment with neuraminidase inhibitor may prevent platelet clearance by anti-αIIb β3 antibodies.
Keywords: Fc receptor; Glanzmann thrombasthenia; immune thrombocytopenia; neuraminidase; oseltamivir.
© 2019 International Society on Thrombosis and Haemostasis.