Anti-c-Mpl antibody-positive acquired amegakaryocytic thrombocytopenia with immune thrombocytopenia-like features in mixed connective tissue disease

Abstract

Acquired amegakaryocytic thrombocytopenia is a rare cause of severe thrombocytopenia characterized by a marked reduction in bone marrow megakaryocytes and may be difficult to distinguish clinically from immune thrombocytopenia. Acquired amegakaryocytic thrombocytopenia has been reported in various autoimmune and non-autoimmune conditions but has not previously been described in a patient with mixed connective tissue disease. We describe the case of a 63-year-old woman with longstanding mixed connective tissue disease who developed severe thrombocytopenia with mucosal bleeding and purpura. Although she was initially treated for presumed immune thrombocytopenia with platelet transfusion, prednisolone, and intravenous immunoglobulin, followed by intravenous methylprednisolone pulse therapy, her platelet count failed to improve. A subsequent bone marrow biopsy revealed relatively preserved erythroid and granulocytic haematopoiesis with a marked reduction in megakaryocytes, and acquired amegakaryocytic thrombocytopenia was diagnosed after myelodysplastic syndrome and leukaemia had been excluded. Treatment with rituximab and eltrombopag resulted in rapid platelet recovery, and remission has been sustained for 14 months, including after two maintenance rituximab doses administered during follow-up. Testing performed during follow-up revealed positivity for an antibody against the thrombopoietin receptor, suggesting a possible immune-mediated mechanism of impaired megakaryopoiesis. The markedly elevated immature platelet fraction and platelet-associated immunoglobulin G also raised the possibility of concomitant immune thrombocytopenia-like peripheral platelet destruction. This case highlights the importance of considering acquired amegakaryocytic thrombocytopenia in patients with systemic autoimmune disease and severe thrombocytopenia refractory to corticosteroids or intravenous immunoglobulin, while recognizing that impaired platelet production and peripheral platelet destruction may overlap.