Update on chronic immune thrombocytopenic purpura (ITP)

Platelet production and circulation Thrombopoietin (TPO), the major cytokine affecting all phases of platelet production, is produced primarily by the liver and binds to the c-Mpl receptor located on platelets, stem cells and megakaryocytes. Upon stimulation, pluripotential stem cells produce cells committed to megakaryocyte differentiation. These cells initially undergo mitosis followed eventually by endomitosis resulting in a progressive increase in size with cells ranging from 2N to 64N and a proportional cytoplasmic increase. Platelet formation occurs in the cytoplasm and the number of platelets produced/megakaryocyte is roughly proportional to megakaryocyte size. Platelet production is regulated as follows: the liver produces a constant quantity of TPO each day and a large portion of this binds to circulating platelets; unbound TPO is available to stimulate platelet production. In thrombocytopenic states due to reduced platelet production, less TPO is adsorbed by circulating platelets and more is available to stimulate platelet production. In ITP, TPO levels are normal or slightly increased probably due to TPO binding to platelets which are then destroyed, removing TPO from the circulation.