Diminished platelet production
The role of platelet destruction in ITP is well known. However, recent findings have shown that suboptimal platelet production also plays an important role. One might expect ITP patients to have high levels of TPO, but paradoxically, TPO levels may be decreased, normal, or only modestly increased in patients with ITP, rather than the expected compensatory increases seen with thrombocytopenia due to other causes. Increased platelet destruction leads to increased TPO destruction, resulting in less TPO available to stimulate platelet production.3-7
Additionally, while levels of megakaryocytes are often increased in ITP, most of these megakaryocytes are small and probably immature, and autoantibodies may have damaged them. Evidence suggests these megakaryocytes are not as productive as normal ones.3,4,5,7
References
3. Gernsheimer T. Pathophysiology and thrombokinetics in autoimmune thrombocytopenia. Blood Rev. 2002;16:7-8.
4. Houwerzijl EJ, Blom NR, van der Want JJL, et al. Ultrastructural study shows morphologic features of apoptosis and para-apoptosis in megakaryocytes from patients with idiopathic thrombocytopenic purpura. Blood. 2004;103:500-506.
5. Emmons RVB, Reid DM, Cohen RL, et al. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction. Blood. 1996;87:4068-4071.
6. Nichol JL. Endogenous TPO (eTPO) levels in health and disease: possible clues for therapeutic intervention. Stem Cells. 1998;16(suppl 2):165-175.
7. Kaushansky K. The molecular mechanisms that control thrombopoiesis. J Clin Invest. 2005;115:3339-3347.
