Thrombopoietin receptor agonists in the treatment of thrombocytopenia

The basis of treatment for immune thrombocytopenic purpura (ITP) has conventionally relied on nonspecific immune suppression designed to reduce platelet destruction. As a consequence, at least half of the morbidity and mortality in this condition is related to infection secondary to treatment, and alternative treatments are desirable.

It has been shown that ITP is not purely due to 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, which had no sequence homology to endogenous TPOs, studies confirmed clinical effect. Two agents, romiplostim and eltrombopag, are now licensed and their place in the treatment is being evaluated.

Platelet responses to romiplostim and eltrombopag 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 presplenectomy or postsplenectomy. 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.