Immune attack on megakaryocytes in immune thrombocytopenia

A State of the Art lecture titled “Immune Attack on Megakaryocytes in ITP: The Role of Megakaryocyte Impairment” was presented at the International Society on Thrombosis and Haemostasis Congress in 2023. Immune thrombocytopenia (ITP) is an acquired autoimmune disorder caused by autoantibodies against platelet surface glycoproteins that provoke increased clearance of circulating platelets, leading to reduced platelet number. However, there is also evidence of a direct effect of antiplatelet autoantibodies on bone marrow megakaryocytes. Indeed, immunologic cells responsible for autoantibody production reside in the bone marrow; megakaryocytes progressively express during their maturation the same glycoproteins against which ITP autoantibodies are directed, and platelet autoantibodies have been detected in the bone marrow of patients with ITP. In vitro studies using ITP sera or monoclonal antibodies against platelet and megakaryocyte surface glycoproteins have shown an impairment of many steps of megakaryopoiesis and thrombopoiesis, such as megakaryocyte differentiation and maturation, migration from the osteoblastic to the vascular niche, adhesion to extracellular matrix proteins, and proplatelet formation, resulting in impaired and ectopic platelet production in the bone marrow and diminished platelet release in the bloodstream. Moreover, cytotoxic T cells may target bone marrow megakaryocytes, resulting in megakaryocyte destruction. Altogether, these findings suggest that antiplatelet autoantibodies and cellular immunity against bone marrow megakaryocytes may significantly contribute to thrombocytopenia in some patients with ITP. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress. The complete unraveling of the mechanisms of immune attack–induced impairment of megakaryopoiesis and thrombopoiesis may open the way to new therapeutic approaches.