Bone marrow fibrosis in thrombopoietin treated patients-biochemical markers and mechanisms
Bone marrow fibrosis in thrombopoietin treated ITP patients
No evidence of progressive bone marrow fibrosis was found upon sustained exposure to thrombopoietin agonists for the treatment of immune thrombocytopenia (ITP)
We completed three studies, two retrospective (both are published- one in Modern pathology and one The British Journal of Haematolgy), and one prospective study on bone marrow fibrosis and collagen metabolites in thrombopoietin agonists treated ITP patients (manuscript in preparation). In these two studies, we showed that thrombopoietin agonists induced an initial increase in bone marrow fibrosis, however, there was no evidence of further increase in fibrosis upon sustained exposure to these agents. In the prospective study we expanded the study material and included sequential measurements of a number of connective tissue metabolites in serum (including pocollagen I and III, ICTP and hyaluronan), growth factors (including Transforming growth factor and fibroblast growth factor) and cytokines (TNFalfa, IFN, IL10) to validate our results and to explore underlying mechanisms. Studying markers of collagen synthesis and degradation showed that collagen production increased initially but declined during the second year upon continuous exposure to TPO, while its degradation remained unchanged resulting in possible decrease in collagen deposition with time. The same pattern was observed with various growth factors that are known to be associated with fibrosis. The possible explanation of this finding is that thrombopoietin agonists alters the immunological response of ITP or they induce megakaryocyte maturation thus limiting the release of fibrosis inducing growth factors. This effect of thrombopoietin agonists has not been described before. The study also confirms the safety of these agents.
Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents.
Br J Haematol 2011 Oct;155(2):248-55. Epub 2011 sep 9
Thrombopoietin receptor agonist therapy in primary immune thrombocytopenia is associated with bone marrow hypercellularity and m