Immune thrombocytopenic purpura

Abstract

The disease that was formerly termed idiopathic thrombocytopenia (ITP), is becoming far better understood, so much so that the same acronym has been reworked, to mean immune thrombocytopenia. Recent progress using murine models of the disease has shed new insights into the mechanisms of platelet destruction (both B and T cell mediated), and have lead to a growing appreciation that megakaryopoiesis is impaired in the disease. It is also clear that novel approaches to therapy are upon us. For example, while 1mg/kg of prednisone was standard of care for decades, high doses of dexamethasone are being appreciated as a potentially disease modifying treatment. While many (or most) patients will respond to glucocorticoid therapy, most relapse once the drug is discontinued. In contrast, while anti-B cell antibody therapy does not yield as high an initial response rate as glucocorticoids, when they do occur remissions tend to be more long-lasting. As such, newer approaches emphasise the combination of high dose glucocorticoids plus anti-B-cell antibodies. With the cloning and characterisation of thrombopoietin, a number of drugs have emerged that bind to and stimulate the thrombopoietin receptor. Two of these drugs have now received US Food and Drug Administration approval for use in patients with chronic refractory ITP. The appropriate use of such agents has not yet been rigorously determined, but it is clear that a subset of patients can benefit from such agents. Finally, in this era of ‘targeted therapy', the urge to shed old standards is strong. Nevertheless, recent long term follow up studies, and meta-analyses have suggested that splenectomy should remain as an important element in our approach to patients with chronic ITP. The mechanisms of impaired platelet formation and survival, and newer approaches to therapy will be reviewed in this talk.