Abstract

Platelet production must be tightly regulated to avoid spontaneous bleeding or arterial occlusion and organ damage. Multifaceted and complex mechanisms control platelet production and removal in physiological and pathological conditions. It recent years it has become apparent that changes in platelet glycosylation affects platelet survival. Recently, we provided evidence that platelets become desialylated as they circulate and age in blood. Binding of desialylated platelets to the hepatic Ashwell-Morell receptor (AMR) induces hepatic expression of thrombopoietin (TPO) mRNA and protein through Janus kinase 2 (JAK2) and the acute phase response signal transducer and activator of transcription 3 (STAT3), thereby regulating platelet production. Recognition of this newly identified physiological feedback mechanism contributes to an understanding of the pathophysiology of platelet diseases, such as essential thrombocythemia and immune thrombocytopenia, and contributes to an understanding of the mechanisms of thrombocytopenia observed with JAK1 /2 inhibition. Our work further suggests the existence of novel communication between desialylated platelets, hepatocytes and bone marrow, which goes beyond that of TPO production. This data shows that changes in glycosylation and posttranslational modifications are powerful communicators and modifiers of hematopoiesis.