A unique phenotype of acquired Glanzmann thrombasthenia due to non-function-blocking anti-αIIbβ3 autoantibodies

Essentials Acquired Glanzmann thrombasthenia (aGT) is generally caused by function-blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of alpha IIb beta 3 with anti-alpha IIb beta 3 Abs. The anti-alpha IIb beta 3 Abs of the patient did not inhibit platelet function but reduced surface alpha IIb beta 3. Internalization of alpha IIb beta 3 induced by the Abs binding may be responsible for the phenotype. Background Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-alpha IIb beta 3 autoantibodies. Aim We characterize an unusual case of aGT caused by marked reduction of surface alpha IIb beta 3 with non-function-blocking anti-alpha IIb beta 3 antibodies (Abs). Methods A 72-year-old male suffering from immune thrombocytopenia since his 50s showed exacerbation of bleeding symptom despite mild thrombocytopenia. Platelet aggregation was absent with all agonists but ristocetin. Analysis of alpha IIb beta 3 expression and genetic analysis were performed. We also analyzed effects of anti-alpha IIb beta 3 Abs of the patient on platelet function and alpha IIb beta 3 expression. Results Surface alpha IIb beta 3 expression was markedly reduced to around 5% of normal, whereas his platelets contained alpha IIb beta 3 to the amount of 40-50% of normal. A substantial amount of fibrinogen was also detected in his platelets. There were no abnormalities in ITGA2B and ITGB3 cDNA. These results indicated that reduced surface alpha IIb beta 3 expression caused a GT phenotype, and active internalization of alpha IIb beta 3 was suggested. Anti-alpha IIb beta 3 IgG Abs were detected in platelet eluate and plasma. These Abs did not inhibit PAC-1 binding, indicating that the Abs were non-function-blocking. Surface alpha IIb beta 3 expression of a megakaryocytic cell line and cultured megakaryocytes tended to be impaired by incubation with the patient's Abs. After 2 years of aGT diagnosis, his bleeding symptom improved and surface alpha IIb beta 3 expression was recovered to 20% of normal with reduction of anti-alpha IIb beta 3 Abs. Conclusion We demonstrated a unique aGT phenotype due to marked reduction of surface alpha IIb beta 3. Internalization induced by anti-alpha IIb beta 3 Abs may be responsible in part for the phenotype.