Thrombopoietin: too much or too little

The basis of treatment for immune thrombocytopenia (ITP) has conventionally relied on non-specific immune suppression designed to reduce platelet destruction. As a consequence, at least half of the morbidity and mortality in the condition is related to infection secondary to treatment and alternate treatments are desirable. It has been shown that ITP is not purely due platelet destruction and in a significant proportion platelet production is suboptimal. Further interest developed with the discovery that the recombinant thrombopoietins (TPOs) could enhance platelet production in a variety of thrombocytopenic states. With the development of the second generation of TPOs that had no sequence homology to endogenous TPO, studies confirmed clinical effect. Two agents, romiplostim and eltrombopag, are now licensed and their place in the treatment is being evaluated. Platelet responses are seen in a much greater percentage than in other second-line studies, and these are maintained while the drugs continue to be administered. Both are well tolerated with no significant adverse effects over placebo and have an effect both pre- and post-splenectomy. An interesting initial observation has been that the platelet response is associated with an improved quality of life in many patients when compared with conventional management. Clinical trials are also being conducted in patients with thrombocytopenia relating to liver disease, HCV infection, myelodyplasia, and post-chemotherapy.