Platelet Destruction and the TPO Paradox

The process of platelet destruction is accelerated in ITP patients. Antiplatelet immunoglobulin G (IgG) autoantibodies bind to antigens on the cell membranes of platelets.¹ These platelets apparently continue to function normally, but are marked for premature destruction in the reticuloendothelial system (primarily in the spleen).² When there are fewer platelet receptors with which to bind, levels of the growth hormone thrombopoietin (TPO) usually rise, stimulating the production of more platelets.^3,4

Though one might expect ITP patients to have high levels of TPO in response to accelerated platelet destruction, TPO levels may be decreased, normal, or only modestly increased in patients with ITP. This is counter to the compensatory increases in TPO seen with thrombocytopenias due to other causes.^5,6 The relative TPO deficiency, compared with other thrombocytopenias, may contribute to the ineffective platelet production in response to the drop in platelet count.^5,7 This failure of compensatory platelet production gives ITP its unique identity.

TPO and Platelet Production

Why do TPO levels fail to increase in ITP patients? Although platelet production is not increased in response to low platelet levels, the bone marrow of ITP patients contains a normal or even higher number of megakaryocytes.⁸ This stability in the total megakaryocyte mass may help to explain the unchanged levels of TPO seen in ITP.¹ Evidence, however, suggests that most of these megakaryocytes are small, probably immature, and not as productive as normal ones. They may have suffered damage from antibodies.^1,6 Again, these abnormalities are not seen in other autoimmune cytopenias and suggest a unique mechanism for ITP.^1,6