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Immune Thrombocytopenia (ITP) is the commonest acquired thrombocytopenia after chemotherapy-induced thrombocytopenia. Existing guidelines describe the management and treatment of most patients who overall do well, even if they present with chronic disease, and are usually not at high risk of bleeding. However, a small percentage of patients is refractory and difficult to manage. Patients classified as refractory either have a diagnosis that is not really ITP or have disease that is difficult to manage. ITP is a diagnosis of exclusion; no specific tests exist to confirm the diagnosis. Response to treatment is the only affirmative confirmation of diagnosis. However, refractory patients do not respond to front-line or other treatments, and thus, no confirmation of diagnosis exists. This review carefully evaluates the diagnostic considerations in patients with refractory ITP. The second section describes combination treatment for refractory cases of ITP. The reported combinations are divided into the era before thrombopoietin(TPO) and rituximab and the current era. Current therapy appears to have increased effectiveness. However, the definition of refractory, if it includes insufficient response to TPO agents, describes a group with more severe and difficult to treat disease. The biology of refractory ITP is largely unexplored and includes oligoclonality, lymphocyte pumps, and other possibilities. Newer treatments, especially rapamycin, fostamatinib, FcRn and BTK inhibitors, may be useful components of future therapy given their mechanisms of action but TPO agents, notwithstanding failure as monotherapy, appear to be critical components. In summary, refractory ITP is a complicated entity in which precise, specific diagnosis is as important as development of effective combination treatments.
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Chronic refractory anemia with granulocytopenia, and/or thrombocytopenia. Myeloblasts and progranulocytes constitute 5 to 40 percent of the nucleated marrow cells.
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The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.
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