These refractory patients have not necessarily undergone splenectomy. Therefore, we reserve the description of “refractory” for patients whose platelet counts do not respond to ≥2 treatments, there is no single medication to which they respond, and their platelet counts are very low and accompanied by bleeding. 11 Thus, splenectomy may not be performed in otherwise refractory patients. Furthermore, there is a reluctance to pursue splenectomy when other treatments have been ineffective, based on the not well-documented but widely believed consensus that splenectomy will likely not be effective in such a circumstance. Currently, there is increasing reluctance to undergo or recommend splenectomy among patients and physicians, 10 such that refractory needs to be defined without reference to splenectomy. Failure to respond to splenectomy is included in the definition of “refractory” according to Rodeghiero et al, although this is disputed in children. 9 Ideally the treatment would be repeated to enhance validity of the lack of response. 8 We will use the definition of response as outlined by Rodeghiero et al, achieving a platelet count of 30 000/µL and doubling baseline platelet counts. In patients with refractory disease, a number of agents are likely to have been used, including steroids, IVIG, TPO-RAs, rituximab, and/or others, whereas splenectomy will not necessarily have been performed.ĭefining refractory as “no response to treatment” is subjective. The American Society of Hematology guidelines suggest TPO-RAs be used as the first second-line agent in patients with persistent disease. There are no guidelines to specify the order in which second-line agents should be used. Additional second-line agents include fostamatinib and immunosuppressive agents (eg, azathioprine, cyclosporine, mycophenolate mofetil, and others). Second-line treatment primarily includes thrombopoietin receptor agonists (TPO-RAs) and rituximab, with splenectomy deferred until ≥1 y from diagnosis. 7 First-line therapy usually consists of steroids (high-dose dexamethasone or prednisone) or IV immunoglobulin (IVIG), or even a combination of both for certain patients.
1, 6 However, small groups of patients exist who are very difficult to manage and do not respond to any treatment (ie, have refractory disease).Ĭurrent treatment of ITP is not strictly regimented. 5 Most patients can usually be managed with conventional treatment. Adults with ITP do not improve as often as children, but they have a higher rate of improvement than generally recognized, perhaps as much as 40% over 1 year and 60% over 3 years.
1 - 4 Most children with ITP have good outcomes with a substantial rate of spontaneous improvement, and those who require intervention or progress to chronic disease usually respond well to treatment. Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder with thrombocytopenia resulting from increased platelet destruction and inhibition of platelet production. In summary, refractory ITP is a complicated entity in which a precise specific diagnosis is as important as the development of effective combination treatments. Newer treatments, especially rapamycin, fostamatinib, FcRn, and BTK inhibitors, may be useful components of future therapy given their mechanisms of action however, TPO agents, notwithstanding failure as monotherapy, appear to be critical components. The biology of refractory ITP is largely unexplored and includes oligoclonality, lymphocyte pumps, and other possibilities. However, the definition of refractory, if it includes insufficient response to TPO agents, describes a group with more severe and difficult-to-treat disease. Current therapy appears to have increased effectiveness. The reported combinations are divided into the era before thrombopoietin (TPO) and rituximab and the current era. The second section describes combination treatment for refractory cases of ITP. The first section of this review carefully evaluates the diagnostic considerations in patients with refractory ITP. However, refractory patients do not respond to front-line or other treatments thus, no confirmation of diagnosis exists. Response to treatment is the only affirmative confirmation of diagnosis. ITP is a diagnosis of exclusion no specific tests exist to confirm the diagnosis.
Patients classified as refractory have a diagnosis that is not really ITP or have disease that is difficult to manage. Existing guidelines describe the management and treatment of most patients who, overall, do well, even if they present with chronic disease, and they are usually not at a high risk for bleeding however, a small percentage of patients is refractory and difficult to manage. Immune thrombocytopenia (ITP) is the most common acquired thrombocytopenia after chemotherapy-induced thrombocytopenia.
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