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Interleukin-6 and the Lung
Published in Jason Kelley, Cytokines of the Lung, 2022
Ralph J. Zitnik, Jack A. Elias
Several lines of evidence suggest that IL-6 is an important regulator of thrombopoiesis. Thrombocytosis is observed in transgenic mice that overexpress IL-6 (Suematsu et al., 1989). Intravenously infused recombinant IL-6 also causes an increase in peripheral platelet counts in normal mice (Ishibashi et al., 1989), mice recovering from radiation-induced marrow injury (Patchen et al., 1991), and normal primates (Asano et al., 1990). Interestingly, mice made acutely thrombocytopenic with antiplatelet antiserum have increased systemic IL-6 levels and increased levels of IL-6 mRNA in their spleen and marrow during recovery (Cox et al., 1991). Megakaryocytes produce IL-6 and express the IL-6 receptor. Interleukin-6 increases megakaryocyte precursor proliferation, and induces megakaryocyte terminal differentiation (Quesenberry et al., 1991; Teramura et al., 1989; Bruno and Hoffman, 1989). It also accelerates megakaryocyte maturation, as assessed by indexes such as cell ploidy, size, acetylcholinesterase expression, and von Willebrand’s factor secretion (Ishibashi et al., 1989; Teramura and Mizoguchi, 1990). Interestingly, recent studies suggest that IL-6–induced thrombocytosis is, to a significant degree, due to the ability of IL-6 to stimulate platelet maturation, rather than its effects on the proliferation of early platelet precursors (Williams et al., 1990; Lotem et al., 1989).
Congenital Amegakaryocytic Thrombocytopenia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
During thrombopoiesis, a pluripotent hematopoietic stem cell divides and forms myeloid stem cell which makes early commitment to megakaryoblast. After undergoing further division, megakaryoblast becomes immature megakaryocyte which completes its terminal differentiation into mature megakaryocytes and finally platelet that possesses many polyploid nuclei, extensive intracellular organelles (for platelet function), and membrane structures (for platelet shedding) [2,3].
Platelet Disorders Douglas Triplett
Published in Genesio Murano, Rodger L. Bick, Basic Concepts of Hemostasis and Thrombosis, 2019
Thrombocytopenia is a relatively consistent finding in patients with megaloblastic hematopoiesis. The thrombocytopenia is due to ineffective thrombopoiesis, which is characterized by diminished platelet production despite the presence of an increased marrow megakaryocytic mass.175 The abnormality in production is presumed to be secondary to impaired DNA synthesis and a resulting limitation in the nuclear endo-reduplication.215 In the Wright’s stained bone marrow, megakaryocytes will often appear hyperlobulated and platelets abnormally large. In addition to the abnormal maturation in the bone marrow, a moderate shortening of platelet survival has been described.216 Ineffective thrombopoiesis has also been seen in DiGuglielmo’s syndrome, paroxysmal nocturnal hemoglobinuria, certain forms of preleukemia, and acute myelomonocytic leukemias.
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
The development of megakaryocytes from bone marrow stem cells is driven by many cytokines and TPO plays a central role at each stage of thrombopoiesis from stem cells to platelets. In China, rhTPO was recommended as a prophylactic option for severe thrombocytopenia after chemotherapy and its application has achieved good results [10]. Owing to the difficulties of CIT treatment and seriousness of bleeding consequences, TPO-RA was considered as an alternative therapeutic option for patients with poor response to rhTPO. More than 80% (44/52) of patients with CIT resumed chemotherapy with weekly romiplostim compared to one of the eight control patients [11]. EPAG treatment shortened the time to recover from platelet nadir in patients treated with gemcitabine-based chemotherapy and resulted in fewer chemotherapy dose delays or reductions [12].
Pathogenic mechanisms contributing to thrombocytopenia in patients with systemic lupus erythematosus
Published in Platelets, 2022
M. Constanza Baroni Pietto, Paola R. Lev, Ana C. Glembotsky, Cecilia P. Marín Oyarzún, Graciela Gomez, Victoria Collado, Cecilia Pisoni, Ramiro A. Gomez, Matías Grodzielski, Jacqueline Gonzalez, Karina V. Mariño, Paula G. Heller, Nora P. Goette, Rosana F. Marta
Platelet production involves a complex sequence of events that drive undifferentiated hematopoietic progenitors through two well-individualized processes, megakaryopoiesis and thrombopoiesis. The first one involves hematopoietic progenitor commitment to the megakaryocytic lineage, proliferation, differentiation and maturation, to give rise to mature megakaryocytes (Mks). The second one comprises a complex reorganization of mature Mks cytoskeletal components and organelles in order to produce cytoplasmic extensions called proplatelets (PP), which elongate and branch, and finally, give birth to platelets from their tips [13]. Both steps, megakaryopoiesis and thrombopoiesis, were described to be impaired in ITP [14–16], providing another mechanism leading to thrombocytopenia in this setting. Conversely, megakaryocyte development and platelet generation have not been investigated in thrombocytopenic SLE patients. In a previous study, we have found the coexistence of mechanisms that leads to peripheral platelet clearance and decreased platelet production in a group of patients with ITP [17].
Platelets after burn injury – hemostasis and beyond
Published in Platelets, 2022
B. Z. Johnson, A. W. Stevenson, L. W. Barrett, M. W Fear, F. M. Wood, M. D. Linden
Platelet counts have prognostic implications in burn survivors, as low platelet counts (65% decrease from baseline, or <100 × 109 platelets/L, at 3 days), and a lack of reactive thrombocytosis, have been correlated with both non-survival and sepsis in patients with severe burns [34,35,38,40,41]. Thrombocytopenia is of concern in ICU, as patients are at risk of hemorrhage and have increased transfusion requirements [42]. Sepsis presents several issues with regard to platelets in burn injuries: first, platelets are involved and may exacerbate the inflammatory process, which may progress to severe inflammatory response syndrome (SIRS) [43]. Second, burn injuries increase circulating levels of thrombopoietin (TPO), which is higher again during sepsis [44]. TPO increases platelet reactivity to other agonists and may contribute to hypercoagulability [45]. Elevated TPO drives thrombopoiesis, leading to thrombocytosis, however the consumption of platelets during coagulation and sepsis keeps absolute platelet counts low early after injury [46]. Studies of sepsis have shown immature platelet fraction, an index of thrombopoiesis and platelet consumption, is highest in patients with the lowest absolute platelet counts [46].