Effects of Hypoxia on Thrombocytopoiesis and Thrombopoietin Production of Mice

McDonald, T. P.; Cottrell, Marilyn; Clift, Rose

doi:10.3181/00379727-160-40445

Cited by 8 publications

(7 citation statements)

References 4 publications

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“…Long-term hypoxia has been demonstrated to increase erythropoiesis while concurrently decreasing thrombocytopoiesis (2). Platelet counts (1-3), percentage of 35S incorporation into platelets (1)(2)(3)(4), colonyforming unit-megakaryocyte populations (5), megakaryocyte precursor cells (5,6), and megakaryocyte concentrations in the bone marrow and spleen (7) have all been shown to be suppressed in mice held in an environment with low oxygen tensions, whereas packed cell volumes of these animals were increased (1)(2)(3)(4)(5)(6)(7)(8).…”

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confidence: 99%

“…Platelet counts (1-3), percentage of 35S incorporation into platelets (1)(2)(3)(4), colonyforming unit-megakaryocyte populations (5), megakaryocyte precursor cells (5,6), and megakaryocyte concentrations in the bone marrow and spleen (7) have all been shown to be suppressed in mice held in an environment with low oxygen tensions, whereas packed cell volumes of these animals were increased (1)(2)(3)(4)(5)(6)(7)(8). In hypoxic mice, increased erythropoietin (EPO) titers (9) and normal thrombopoietin levels (2) have been demonstrated, thereby supporting the hypothesis (1)(2) that the marked stimulation of the erythroid cell line results in competition between precursor cells of the erythrocytic and megakaryocytic cell lines (stem cell competition). In this hypothesis, increased erythropoiesis leads to decreased numbers of cells in the megakaryocytic cell lineage, which leads to decreased thrombocytopoiesis.…”

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confidence: 99%

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Thyroxine Suppresses Thrombocytopoiesis and Stimulates Erythropoiesis in Mice

Sullivan¹,

McDonald²

1992

Experimental Biology and Medicine

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Thyroxine has been shown in vitro to stimulate erythropoiesis by two mechanisms: a direct, beta 2-adrenergic receptor-mediated stimulation of red cell precursors, and an indirect, erythropoietin-mediated mechanism. Clinical reports have suggested that excess thyroxine also exerts depressive effects on thrombocytopoiesis, but the most sensitive methods of assessing platelet production, i.e., percentage of 35S incorporation into platelets and determination of megakaryocyte size and number, are not appropriate for analysis of platelet production in human patients. The purpose of this study was to use a mouse model to investigate the effects of the hyperthyroid state on erythropoiesis and thrombocytopoiesis, and to assess in vivo the two mechanisms by which thyroxine has been described to stimulate erythropoiesis in vitro. We found that thyroxine administration significantly depressed platelet production and stimulated erythropoiesis in mice. Both the D- and L-isomers of thyroxine in appropriate doses produced this depression of thrombocytopoiesis, and the effect was dose dependent for both isomers. Daily administration of thyroxine:increased blood volume; decreased the peripheral platelet count, total circulating platelet count and mass, percentage of 35S incorporation into platelets, and megakaryocyte number and size; and concurrently increased indices of red cell production (packed cell volume, red blood cell count, total circulating red blood cell count and mass, and reticulocyte count). Additionally, propranolol, a nonspecific beta-blocker, partially reversed the suppression of platelet production by L-thyroxine, lending credence to the assertion that the direct, beta 2-adrenergic receptor-mediated stimulation of the erythroid cell line by thyroxine reported to exist in vitro may also be important in vivo.

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confidence: 99%

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confidence: 99%

Thyroxine Suppresses Thrombocytopoiesis and Stimulates Erythropoiesis in Mice

Sullivan¹,

McDonald²

1992

Experimental Biology and Medicine

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“…There is good evidence that platelet production is reduced [80,83,84,86,87,97] and this may be due to a decrease in megakaryocyte differentiation since hypoxia directly suppresses megakaryocyte differentiation and maturation [97]. There is also good evidence for stem cell competition between the erythrocyte and megakaryocyte cell lines [84,86,87]. It is well known that hypoxia stimulates red cell production and this effect could cause a reduction in platelet production due to competition for a common progenitor of these two cell lines.…”

Section: Mechanism By Which Hypoxia Alters Platelet Numbermentioning

confidence: 92%

“…It may be due to a decrease in platelet production [80,83,84], an increase in platelet destruction [83] or platelet sequestration, perhaps in the lungs and spleen [62,81]. There is good evidence that platelet production is reduced [80,83,84,86,87,97] and this may be due to a decrease in megakaryocyte differentiation since hypoxia directly suppresses megakaryocyte differentiation and maturation [97]. There is also good evidence for stem cell competition between the erythrocyte and megakaryocyte cell lines [84,86,87].…”

Section: Mechanism By Which Hypoxia Alters Platelet Numbermentioning

confidence: 96%

“…In experimentallyinduced hypoxia, 3 weeks of intermittent asphyxia in rats, mimicking the intermittent asphyxia of human sleep apnoea, has no effect on platelet number but increases platelet aggregation [79]. There is good evidence that either hypobaric or normobaric continuous hypoxia causes thrombocytosis in the short-term (perhaps several hours to several days) but causes thrombocytopaenia in the longterm (perhaps several weeks) in rats [51,80,81], mice [82][83][84][85][86][87] and rabbits [88] although one study in rats reported long-term thrombocytosis [89]. The short-term thrombocytosis is observable when measured as early as one day after exposure to hypoxia [80,82,84,88] but the time course of changes in count during the first 24 hours, which would be more relevant to air travel, do not appear to have been measured in animal studies.…”

Section: Hypoxia and Platelet Number And Functionmentioning

confidence: 99%

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The Role of Hypoxia and Platelets in Air Travel-Related Venous Thromboembolism

Bradford

2007

CPD

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Although somewhat controversial, there is good evidence that long-distance travel in general is a risk factor for venous thromboembolism, even in the absence of other risk factors. This is probably due to effects consequent to prolonged sitting but air travel in particular may be associated with risk factors other than this. One likely factor is hypoxia caused by the low ambient pressure of aircraft cabins. There is an association between venous thromboembolism and the hypoxia of altitude, chronic respiratory disease, neonatal hypoxia, sleep apnoea and experimentally-induced hypoxia. Platelet number and/or function are altered in all of these circumstances. Platelet aggregation is pivotal to venous thromboembolism and hypoxia alters platelet number and function. The early-onset thrombocytosis caused by hypoxia may be due to increased release of platelets from megakaryocytes and the late-onset thrombocytopaenia may be due to decreased platelet production and/or stem cell competition between erythrocytes and megakaryocytes. Hypoxia-induced platelet activation and aggregation may be due to increased circulating catecholamine levels but it is not known whether hypoxia can affect platelets directly. There is a need for further studies on the possible involvement of hypoxia-induced changes in platelet number and function in air travel-related venous thromboembolism.

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Long-term adaptation to hypoxia preserves hematopoietic stem cell function

Chen

Kang

Keyvanfar

et al. 2016

Experimental Hematology

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Molecular oxygen sustains aerobic life, but it also serves as the substrate for oxidative stress, which has been associated with the pathogenesis of disease and with aging. Compared with mice housed in normoxia (21% O2), reducing ambient oxygen to 10% O2 (hypoxia) resulted in increased hematopoietic stem cell (HSC) function as measured by bone marrow (BM) cell engraftment onto lethally irradiated recipients. The number of BM c-Kit(+)Sca-1(+)Lin(-) (KSL) cells as well as the number of cells with other hematopoietic stem and progenitor cell markers were increased in hypoxia mice, whereas the BM cells' colony-forming capacity remained unchanged. KSL cells from hypoxia mice showed a decreased level of oxidative stress and increased expression of transcription factor Gata1 and cytokine receptor c-Mpl, consistent with the observations of increased erythropoiesis and enhanced HSC engraftment. These observations demonstrate the benefit of a hypoxic HSC niche and suggest that hypoxic conditions can be further optimized to preserve stem cell integrity in vivo.

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Effects of Hypoxia on Thrombocytopoiesis and Thrombopoietin Production of Mice

Cited by 8 publications

References 4 publications

Thyroxine Suppresses Thrombocytopoiesis and Stimulates Erythropoiesis in Mice

Thyroxine Suppresses Thrombocytopoiesis and Stimulates Erythropoiesis in Mice

The Role of Hypoxia and Platelets in Air Travel-Related Venous Thromboembolism

Long-term adaptation to hypoxia preserves hematopoietic stem cell function

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