Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an incompletely understood pathophysiology, but includes platelet-clearance in the spleen and liver via T-cells and/or platelet... Show moreImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder with an incompletely understood pathophysiology, but includes platelet-clearance in the spleen and liver via T-cells and/or platelet-autoantibodies. Strikingly, thrombopoietin (TPO) levels remain low in ITP. Platelet-glycoprotein (GP)Ibα has been described to be required for hepatic TPO generation, however, the role of GPIb-antibodies in relation to platelet hepatic sequestration and TPO-levels, with consideration of platelet counts, remains to be elucidated. Therefore, we performed a study in which we included 53 chronic and non-splenectomized ITP patients for which we conducted indium labeled autologous platelet scintigraphy, measured platelet-antibody profiles and TPO-levels. Upon stratification towards the severity of thrombocytopenia, no negative association was observed between GPIb/IX-antibodies and TPO levels, suggesting that GPIb/IX-antibodies do not inhibit or block TPO levels. Surprisingly, we observed a positive association between GPIb/IX-antibody levels and TPO levels, and GPIb/IX-antibodies and platelet hepatic sequestration, in patients with severe thrombocytopenia, but not in patients with mild or moderate thrombocytopenia. In addition, platelet hepatic sequestration and TPO levels were positively associated. This collectively indicates that GPIb/IX-antibodies may be associated with an increased platelet hepatic sequestration and elevated TPO levels in severe thrombocytopenic ITP patients, however, further research is warranted to elucidate the pathophysiological mechanisms. Show less
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody... Show moreImmune thrombocytopenia (ITP) is an autoimmune bleeding disorder. The pathophysiological mechanisms leading to low platelet levels in ITP have not been resolved, but at least involve autoantibody-dependent and/or cytotoxic T cell mediated platelet clearance and impaired megakaryopoiesis. In addition, T cell imbalances involving T regulatory cells (Tregs) also appear to play an important role. Intriguingly, over the past years it has become evident that platelets not only mediate hemostasis, but are able to modulate inflammatory and immunological processes upon activation. Platelets, therefore, might play an immuno-modulatory role in the pathogenesis and pathophysiology of ITP. In this respect, we propose several possible pathways in which platelets themselves may participate in the immune response in ITP. First, we will elaborate on how platelets might directly promote inflammation or stimulate immune responses in ITP. Second, we will discuss two ways in which platelet microparticles (PMPs) might contribute to the disrupted immune balance and impaired thrombopoiesis by megakaryocytes in ITP. Importantly, from these insights, new starting points for further research and for the design of potential future therapies for ITP can be envisioned. Show less
Jolink, A.T.C.; Nelson, V.S.; Schipperus, M.R.; Amini, S.N.; Vidarsson, G.; Schoot, C.E. van der; ... ; Kapur, R. 2021
Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and... Show moreAutologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and have not been systematically reviewed. Our aim is to systematically review and meta-analyse the association between sequestration pattern and post-splenectomy platelet response. Articles were selected from MEDLINE when they a) included ITP patients, b) performed scintigraphy, and c) included post-splenectomy platelet response. The 23 included studies (published between 1969-2018) represented 2966 ITP-patients. Response to splenectomy occurred most frequently in patients with a splenic pattern (87.1 % in splenic versus 47.1 % in mixed and 25.5 % in hepatic patterns). A pooled analysis of 8 studies showed an odds ratio of 14.21 (95 % CI: 3.65-55.37) for platelet response in the splenic versus the hepatic group. Our findings indicate that a splenic sequestration pattern is associated with better response after splenectomy. Platelet sequestration patterns may be useful in the clinical decision-making regarding splenectomy. Show less
