Autoantibodies in immune thrombocytopenia affect the physiological interaction between megakaryocytes and bone marrow extracellular matrix proteins

Abstract

Immune thrombocytopenia (ITP) is characterized by itsheterogeneity among patients with regard to both clinicalfeatures and response to treatment. Although there isstill much to investigate, this heterogeneity could be thereflection of multiple mechanisms contributing to thrombocytopenia,affecting individual patients in variable proportions.These mechanisms include increased platelet clearanceby autoantibodies targeting main platelet glycoproteins(GPs) (IIbIIIa, IbIX and IaIIa) and impaired megakaryopoiesis(McMillan et al, 2004). Recently, we reported thatITP plasma samples inhibit proplatelet (PP) formation bynormal megakaryocytes (MKs) (Lev et al, 2014), demonstratingthat thrombopoiesis, the key step of platelet production,is altered, a finding further confirmed by others(Iraqi et al, 2015). In agreement with these experimentaldata, studies on platelet kinetics show inadequate plateletproduction according to the degree of thrombocytopenia(Ballem et al, 1987).