Glycosylation changes affect platelet production directly and indirectly. (A) Deficit in the sialyltransferase ST3Gal1 (St3gal1^MK−/−) causes exposure of the cryptic TF antigen that is recognized by a plasmocytoid dendritic-like cell inducing the release of type 1 interferon dampening platelet production. Increased immunoglobulin G antibodies against the TF antigen are observed in pediatric patients with immune thrombocytopenia (ITP). (B) β4GalT1 regulates platelet production. Megakaryocytes derived from B4galt1^−/− mice have an underdeveloped demarcation membrane system, β1 integrin hyperactivity, and impaired platelet production, causing thrombocytopenia. Increased expression and activity of β4GalT1 is observed in megakaryocytes isolated from patients with myeloproliferative neoplasms (MPNs) with high allele burden. Highly galactosylated platelets in MPNs may promote increased hepatic TPO synthesis that sustains the aberrant megakaryopoiesis. IL-6, interleukin 6.