Essentials Acquired Glanzmann thrombasthenia (aGT) is generally caused by function-blocking antibodies (Abs). We demonstrated a unique aGT case due to marked reduction of αIIbβ3 with anti-αIIbβ3 Abs. The anti-αIIbβ3 Abs of the patient did not inhibit platelet function but reduced surface αIIbβ3. Internalization of αIIbβ3 induced by the Abs binding may be responsible for the phenotype. SUMMARY: Background Acquired Glanzmann thrombasthenia (aGT) is a bleeding disorder generally caused by function-blocking anti-αIIbβ3 autoantibodies. Aim We characterize an unusual case of aGT caused by marked reduction of surface αIIbβ3 with non-function-blocking anti-αIIbβ3 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 αIIbβ3 expression and genetic analysis were performed. We also analyzed effects of anti-αIIbβ3 Abs of the patient on platelet function and αIIbβ3 expression. Results Surface αIIbβ3 expression was markedly reduced to around 5% of normal, whereas his platelets contained αIIbβ3 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 αIIbβ3 expression caused a GT phenotype, and active internalization of αIIbβ3 was suggested. Anti-αIIbβ3 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 αIIbβ3 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 αIIbβ3 expression was recovered to 20% of normal with reduction of anti-αIIbβ3 Abs. Conclusion We demonstrated a unique aGT phenotype due to marked reduction of surface αIIbβ3. Internalization induced by anti-αIIbβ3 Abs may be responsible in part for the phenotype.
Keywords: Glanzmann thrombasthenia; autoantibodies; blood platelet disorders; immune thrombocytopenia; integrin αIIbβ3.
© 2018 International Society on Thrombosis and Haemostasis.