Recent advances in the mechanisms and treatment of immune thrombocytopenia

Abstract

Primary immune thrombocytopenia is an autoimmune disease associated with a reduced peripheral blood platelet count. The phenotype is variable with some patients suffering no bleeding whilst others have severe bleeding which may be fatal. Variability in clinical behaviour and treatment responses reflects its complex underlying pathophysiology. Historically the management has relied heavily on immune suppression. Recent studies have shown that the older empirical immune suppressants fail to alter the natural history of the disease and are associated with a poor quality of life for patients. Newer treatments, such as the thrombopoietin receptor agonists, have transformed ITP care. They have high efficacy, are well tolerated and improve patients' quality of life. A greater understanding of the underlying pathophysiology of this disorder has helped develop a number of new targeted therapies. These include inhibitors of the neonatal Fc receptor inhibitors, Bruton tyrosine kinase and complement pathway. Here we discuss the mechanisms underlying ITP and the new approach to ITP care.

The role of platelets in immune-mediated inflammatory diseases

“…Consequently, patients with antiphospholipid antibodies have increased circulating levels of markers of platelet activation, such as soluble CD40L and platelet-derived chemokines 30 , 31 . In addition to antiphospholipid antibodies, antiplatelet antibodies can bind platelets directly, resulting in their activation and/or immune-mediated destruction through complement-dependent cytotoxicity or antibody-dependent phagocytosis 32 . Antiplatelet antibodies target mainly the platelet glycoprotein receptors GPIb–IX (consisting of GPIbα, GPIbβ and GPIX) and GPIa in conjunction with the GPIIb/IIIa complex (also known as CD41/CD61) 33 , and are found in up to 88% of patients with SLE who have immune thrombocytopenia (ITP) 34 .…”

“…Platelet-derived extracellular vesicles in the synovial fluid of patients with rheumatoid arthritis are a source of citrullinated autoantigens, such as citrullinated fibrinogen and vimentin 75 , and thus are decorated with autoantibodies. In addition, activated platelets may be phagocytosed by antigen-presenting cells such as DCs and subsequently processed as foreign antigens 109 , thereby promoting the development of antiplatelet antibodies such as those that are present in the sera of most patients with ITP 32 , in the sera of some patients with SLE and in some other IMIDs 34 , 35 .…”

“…This goal may be reached by developing specific FcγRIIA inhibitors or by the use of high-dose intravenous immunoglobulin 169 , as is currently prescribed in some patients with severe manifestations of IMID. FcγRIIA signals partly through SYK 170 , and the use of a SYK inhibitor such as fostamatinib, which is approved for use in patients with ITP and functions by decreasing platelet phagocytosis by splenic macrophages 32 , may also dampen platelet activation.…”

Immune thrombocytopenic purpura secondary to COVID‐19 vaccination: A systematic review

“…13,14 Even today, it is quite frustrating that ITP remains a diagnosis of exclusion. 15 The most common type of ITP is the idiopathic primary condition, though it can also be found secondary to other conditions, such as systemic autoimmune disorders, medications, a variety of infections, and vaccinations. 14,16 The latter is termed vaccine-associated ITP and has been reported following different types of vaccines.…”

Prospective validation of a biomarker-driven response prediction model to romiplostim in lower-risk myelodysplastic neoplasms – results of the EUROPE trial by EMSCO

“…Both ROM and EPAG stimulate megakaryocyte differentiation and proliferation [23,24]. While the oral small molecule EPAG binds to a transmembrane site of the TPO-receptor [17,25,26] the peptide mimetic ROM binds directly at the extracellular TPO-receptor binding site where also native TPO binds [27][28][29][30]. Until now, both TPO-RA are not approved for the treatment of MDS patients with thrombocytopenia, thus regular platelet transfusions still represent the only supportive treatment option for these patients [16,17].…”