Liver-mediated shedding of platelet GPVI

inhibitory FcgRII expression on splenic macrophages, and these FcgR level changes correlated with increase in platelet counts.Furthermore, clearance of transfused platelets appeared slower in ITP mice treated with romiplostim.These exciting and novel data suggest that TPO-RAs may lower platelet destruction in addition to stimulating platelet production.Nevertheless, the study is still an association.Direct proof that TPO-RAs increase platelet counts or improve transfused platelet survival in ITP by modulating FcgRs will require future studies showing that TPO-RA effects on platelet counts in ITP FcgRII and/or FcgR chain knockout mice are abolished.Several recent studies have shown a sustained platelet response after TPO-RA discontinuation in a subset of ITP patients.10 If the monocyte FcgR balance toward inhibitory FcgRIIb is maintained and the macrophage phagocytic activity remains low in patients who have sustained remission after TPO-RA discontinuation, but not in those who relapse, it would further support the aforementioned effects of TPO-RAs on FcgR modulation and inhibition of platelet destruction in ITP.Questions remain as to the mechanism of action of TPO-RA on monocyte/macrophage FcgR expression and function: does the burst in plasma TGFb1 following TPO-RA treatment 1,8 directly affect and lower phagocytic activity of monocyte/macrophages? Or is the effect mediated through Tregs or Bregs which can regulate monocyte activity?Nonetheless, this research sheds new light on TPO-RA immunomodulation and helps to guide research to uncover a novel mechanism of action of TPO-RAs in ITP treatment.Such investigations will help determine whether the immunomodulatory effects of TPO-RAs are specific to the treatment of ITP immunopathology or whether they can be harnessed for treatment of other autoimmune diseases without causing thrombocytosis.