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Congenital Amegakaryocytic Thrombocytopenia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
Thrombopoietin receptor agonists recognizing a site distinct from thrombopoietin may stimulate a receptor with an extracellular domain mutation and offer a potential treatment for a small subset of patients with CAM. These include Romiplostim (a peptibody interacting with the extracellular domain of the receptor), Eltrombopag (a small molecule binding to the transmembrane region of the receptor), and LGD 4665 (transmembrane domain binding agent), none of which is structurally related to THPO [22].
Immunohematology
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, Armand Glassman
Administration of corticosteroids, by themselves, or associated with rituximab or with a combination of rituximab and cyclosporine are considered as the first line of treatment. Thrombopoietin receptor agonists (thrombopoietin, romiplostim and eltrombopag) appear to also be effective but their evaluation is still in progress. Intravenous gamma globulin (IVIg) and anti-D immunoglobulin were considered as the therapy of choice in the past. Their primary mechanism of action is believed to be the blocking of Fc receptors in phagocytic cells, which would inhibit the ingestion and destruction of antibody-coated platelets. This mechanism is most likely to explain the rapid increase in platelet counts seen after therapy with IVIg is initiated. However, the effects are relatively short-lived, and the use of these agents is now relegated either to cases in which there is an urgent need to raise the platelet numbers or cases not responding to the first-line agents mentioned above.
Case 5
Published in Atul B. Mehta, Keith Gomez, Clinical Haematology, 2017
If the count does not recover spontaneously (e.g. within 2 weeks) or if there is symptomatic bruising, particularly affecting mucous membranes such as the nose and mouth, then treatment is indicated. Prednisolone, starting at 0.5 mg/kg/day and reducing according to response, is the first-line therapy. Intravenous immunoglobulin (0.4 mg/kg/day) for 3–5 days is equally effective, but best reserved for non-responders. The thrombopoietin receptor analogues are a new class of drugs which are used if and when steroids or intravenous immunoglobulin (IVIG) are ineffective. Romiplostin has to be given by parenteral injection whereas eltrombopag can be given orally. Other immunosuppressive drugs (e.g. cyclophosphamide, azathioprine, mycophenolate and the anti-CD20 monoclonal antibody Rituximab) are other possible approaches, but for adults with resistant or relapsed ITP but are generally contraindicated in children.
Clinical and molecular characteristics of acute myeloid leukemia with MPL mutation
Published in Hematology, 2022
Yu Chen, Jundan Xie, Zhen Shen, Jie Shi, Suning Chen, Gang Wang
The myeloproliferative leukemia virus oncogene (MPL), which encodes the thrombopoietin receptor (TPO-R), plays vital roles in not only regulating megakaryopoiesis and platelet production but also supporting the maintenance and self-renewal of hematopoietic stem cells (HSCs) [1]. Recent studies have identified multiple MPL mutations that can lead to severe hematological disorders [2,3]. For example, loss-of-function MPL mutations have been reported in familial aplastic anemia, and gain-of-function MPL mutations are associated with myeloproliferative disorders caused by constitutive signaling [4]. Several studies have revealed that MPL is involved in maintaining the properties of leukemia stem cells (LSCs) and can be a candidate surface marker of LSCs [5]. To the best of our knowledge, MPL mutations have rarely been reported in patients with acute myeloid leukemia (AML). The current study aimed to explore the incidence of MPL mutations and the clinical and molecular characteristics of AML with MPL mutation. Moreover, it emphasized the importance of identifying the characteristics of patients with MPL-mutated (MPL-mut) AML. However, further studies must be conducted to evaluate its correlated mechanism.
Effect of avatrombopag in the management of severe and refractory chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors
Published in Platelets, 2022
Yanting Gao, Qi Liu, Yingying Shen, Yuzhu Li, Keding Shao, Baodong Ye, Yiping Shen, Yuhong Zhou, Dijiong Wu
Thrombopoietin receptor agonist (TPO-RA) increases platelet (PLT) counts by activating the thrombopoietin receptor (c-MPL), promoting the proliferation and maturation of megakaryocytes and subsequently stimulates platelet production. It has been successful in treating immune thrombocytopenia (ITP) and thrombocytopenia in chronic liver disease (CLD). TPO-RA was also reported in the management of CIT, but limited data was available [3]. Eltrombopag (EPAG) was reported to be equally effective as rhTPO in the treatment of CIT in patients with lymphoma who experienced grade 3 or 4 thrombocytopenia [4]. Considering the potential hepatotoxicity and different metabolism characteristics of EPAG in Asian populations, 75–100 mg QD may be the maximum recommended dosage in China. For patients with severe CIT unresponsive to first-line IL-11, rhTPO and EPAG, high-dose avatrombopag could exert a profound effect. Herein, we shared the experience of avatrombopag in the management of CIT with grade 4 thrombocytopenia at our center, and assessed the efficacy as well as safety of the drug.
Hematological parameters and X-ray exposure among medical radiation workers: a systematic review and meta-analysis
Published in Expert Review of Hematology, 2022
Siavash Vaziri, Maryam Mirzaei, Fakhredin Saba, Kharaman Salehi Zahabi, Saleh Salehi Zahabi, Morteza Arab-Zozani
Normal maturation of megakaryocytes and platelet production after exposure of HSCs to ionizing radiation, despite the detrimental effect of radiation on cell cycle and differentiation of HSCs, have been shown [8]. Ionizing radiation can induce both megakaryocytopoiesis and thrombopoiesis [8]. However, some other studies have shown that platelet count in the radiology workers may be decreased or not differ from the control group [1]. Thrombopoietin is one of the major cytokines involved in thrombopoiesis [35]. There is a thrombopoietin receptor on megakaryocytes. Platelet production will be decreased following the reduction of thrombopoietin or thrombopoietin (TPO) receptor [35]. However, the effect of ionizing radiation on TPO and TPO receptor has not been determined, so further studies are needed to explore this issue.