Thrombopoietin physiology (megakaryocyte differentiation, source, regulation)
Core concept
- Thrombopoietin (TPO) = principal regulator of megakaryocyte proliferation, differentiation, and platelet production
- Synthesised constitutively, predominantly by the liver (also kidney, marrow stroma) -- production is not significantly upregulated by low platelet count itself
- Regulation is via platelet/megakaryocyte mass acting as a "sink": TPO binds its receptor (c-Mpl) on platelets and megakaryocytes and is cleared/degraded -> free TPO level is inversely related to platelet/megakaryocyte mass, not directly regulated by feedback synthesis
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