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The 5-year sustained response to rituximab was shown to be 26% for children and 21% for adults [26]. Two studies of one cycle of dexamethasone and rituximab demonstrated the additive if not synergistic effects of the combination, especially in the newly diagnosed and patients with persistent disease. The use of thrombopoietin-receptor agonists is an effective and safe second-line treatment strategy. Two thrombopoietin-receptor agonists were approved for the treatment of chronic ITP in adults by the US Food and Drug Administration (FDA) in 2008 and have as of now been used extensively for treatment of chronic ITP (ITP duration ≥ 1 year) in relapsed and refractory patients. These were romiplostim, a thrombopoietin mimetic formed from peptides (peptibody) and eltrombopag (a small molecule, non-peptide). Thrombopoietin receptor activation with these agents resulted in megakaryocyte precursor proliferation and also elevation of the platelet count in many but not all cases in a variety of different uses.
Thrombotic thrombocytopenic purpura
TTP is a medical emergency, since the mortality of untreated patients exceeds 80%. The mortality is thought to be caused by disseminated microvascular thrombosis which may provoke ischemic injury and multiple organ failure. Ischemic organ injury can affect all organs, but the brain and heart are typically most affected. Acute kidney injury requiring dialysis and resulting in chronic kidney disease is rare. Central nervous system involvement is often manifested by transient focal neurologic abnormalities resulting from micro-infarcts in the brain, which may cause focal neurologic deficits. The mainstay of treatment is plasmapheresis with plasma replacement [32,33]. Plasmapheresis works by removing antibodies directed against the von Willebrand factor cleaving protease, ADAMTS-13. The plasma infused as part of the procedure also provides active ADAMTS-13 protease to the patient, further restoring a more physiologic state of von Willebrand factor multimers. Other treatment modalities in non-responders to plasmapheresis include immune-suppression, not limited to high dose steroids, and B-cell depleting agents (e.g. rituximab). Patients with autoantibodies against ADAMTS-13 do not always manifest TTP, and these antibodies alone are not sufficient to demonstrate the impending relapse of the disease. In the case of TTP, it is considered better to avoid platelet transfusion, which should be reserved for patients with clinically significant bleeding, as severe thrombocytopenia itself is not an indication for platelet transfusion. Conversely, platelet transfusion is probably not as dangerous as it was thought to be a decade ago.
Drug-induced thrombocytopenia/DITP and heparin-induced thrombocytopenia
In the event of drug-induced thrombocytopenia/DITP, it is universal practice to stop the suspected drug immediately. Platelet counts usually recover within several days to 2 weeks. Platelet transfusions may be required to treat patients with severe thrombocytopenia and bleeding. Other supportive measures include high dose intravenous immunoglobulin, a brief course of corticosteroids, or even plasmapheresis. Drug-dependent platelet antibodies can persist for years; thus, patients with a confirmed diagnosis should be counseled to avoid future exposures to the drug (with the possible exception of heparin). Testing at one of the few experienced laboratories can be very helpful in confirming a diagnosis. The diagnosis of heparin-induced thrombocytopenia is based on the clinical setting: a platelet count of 200,000 may have decreased enough in a post-op case as to indicate platelet consumption. The management of heparin-induced thrombocytopenia is based on the immediate discontinuation of heparin and the institution of alternative, immediately active anticoagulation. It is extremely important to prevent additional thrombosis and, for this reason, patients are usually treated with an alternative anticoagulant, even if heparin was given only as a prophylactic measure. Options include direct thrombin inhibitors such as lepirudin or argatroban, which are approved by the FDA. Other medications, such as bivalirudin and fondaparinux, can be used in this setting, but are not FDA-approved for the treatment of heparin-induced thrombocytopenia. Coumadin should not be given in the acute setting, as it can provoke thrombotic complications due to protein C depletion during the first days of use. Therefore, coumadin treatment should be postponed until complete normalization of the platelet count. Platelet transfusions are not a routine component of the treatment of heparin-induced thrombocytopenia, since thrombosis, not bleeding, is the primary clinical problem in this illness.