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
Porcelijn, L.; Schmidt, D.E.; Oldert, G.; Hofstede-van Egmond, S.; Kapur, R.; Zwaginga, J.J.; Haas, M. de 2020
To this day, immune thrombocytopenia (HT) remains a clinical diagnosis made by exclusion of other causes for thrombocytopenia. Reliable detection of platelet autoantibodies would support the... Show moreTo this day, immune thrombocytopenia (HT) remains a clinical diagnosis made by exclusion of other causes for thrombocytopenia. Reliable detection of platelet autoantibodies would support the clinical diagnosis, but the lack of specificity and sensitivity of the available methods for platelet autoantibody testing limits their value in the diagnostic workup of thrombocytopenia. The introduction of methods for glycoprotein-specific autoantibody detection has improved the specificity of testing and is acceptable for ruling in ITP but not ruling it out as a diagnosis. The sensitivity of these assays varies widely, even between studies using comparable assays. A review of the relevant literature combined with our own laboratory's experience of testing large number of serum and platelet samples makes it clear that this variation can be explained by variations in the characteristics of the tests, including in the glycoprotein-specific monoclonal antibodies, the glycoproteins that are tested, the platelet numbers used in the assay and the cutoff levels for positive and negative results, as well as differences in the tested patient populations. In our opinion, further standardization and optimization of the direct autoantibody detection methods to increase sensitivity without compromising specificity seem possible but will still likely be insufficient to distinguish the often very weak specific autoantibody signals from background signals. Further developments of autoantibody detection methods will therefore be necessary to increase sensitivity to a level acceptable to provide laboratory confirmation of a diagnosis of ITP. (C) 2020 The Author(s). Published by Elsevier Inc. Show less
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
Porcelijn, L.; Huiskes, E.; Oldert, G.; Schipperus, M.; Zwaginga, J.J.; Haas, M. de 2018
