A mechanism of ineffective erythropoiesis in  -thalassemia/Hb E disease

Lithanatudom, Pathrapol; Leecharoenkiat, Amporn; Wannatung, Tirawat; Svasti, Saovaros; Fucharoen, Suthat; Smith, Duncan R.

doi:10.3324/haematol.2009.015701

Cited by 33 publications

(28 citation statements)

References 30 publications

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“…The difference in the NRBC counts between patients in the splenectomized versus the nonsplenectomized TI group (54.8 times) was much higher than that observed in the HbH-disease group (8.2 times), suggesting that factors other than splenectomy may influence the increase in NRBCs. The high NRBC counts in TI patients can be ascribed to ineffective hematopoiesis (IE) [24]. NRBCs have been shown to correlate with IE and are absent in patients with hereditary spherocytosis (another hemolytic disease that limits effective erythropoiesis) [25].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Hypertension Risk in Patients with Hemoglobin H Disease: Low Incidence and Absence of Correlation with Splenectomy

Yin¹,

Zhang²,

et al. 2013

Acta Haematol

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Pulmonary hypertension (PHT) is a common complication for patients with β thalassemia intermediate (TI), especially splenectomized patients. However, the frequency and risk factors of PHT in patients with hemoglobin H (HbH) disease is unknown. The purpose of this study was to identify the prevalence of PHT risk manifested as tricuspid regurgitant jet velocity (TRV) ≥2.5 m/s in patients with HbH disease and its correlation with splenectomy. One hundred and ninety-eight patients with HbH disease who visited the 303rd Hospital of the People's Liberation Army (Nanning, China) were investigated. Thirteen subjects (6.5%) were diagnosed as having a risk of PHT. Regression analyses showed that the prevalence of PHT risk was correlated only with age (r = 0.195, p = 0.006) and not with splenectomy. The risk of PHT in patients older than 35 years was 5.7 times (range 1.8-18.6) greater than that for patients younger than 35 years. For splenectomized patients compared to those with HbH disease, patients with TI had a higher frequency of PHT risk, higher nucleated red blood cell counts (46.03 ± 41.11 × 10⁹/l vs. 0.18 ± 1.19 × 10⁹/l, p < 0.001) and a higher platelet counts (837.6 ± 178.9 × 10⁹/l vs. 506.7 ± 146.2 × 10⁹/l, p < 0.001). PHT risk is low in patients with HbH disease and does not correlate with splenectomy. Patients older than 35 years should be monitored regularly.

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Section: Discussionmentioning

confidence: 99%

Pulmonary Hypertension Risk in Patients with Hemoglobin H Disease: Low Incidence and Absence of Correlation with Splenectomy

Yin¹,

Zhang²,

et al. 2013

Acta Haematol

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“…β-Thalassemia/HbE is a common hereditary anemia in Southeast Asia, and carriers present with a wide range of disease severity, ranging from essentially asymptomatic to a severe transfusion-dependent state [16]. The underlying pathophysiology of β-thalassemia is associated with deposition of unmatched α-hemoglobin chains, which is believed to lead to ineffective erythropoiesis through induction of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…The underlying pathophysiology of β-thalassemia is associated with deposition of unmatched α-hemoglobin chains, which is believed to lead to ineffective erythropoiesis through induction of apoptosis. The mechanism by which this phenomenon is induced remains unclear, although it has been proposed that both the precipitation of unmatched α-hemoglobin chains as well as an accumulation of unbound iron could lead to oxidative stress and subsequent cell death [16]. …”

Section: Discussionmentioning

confidence: 99%

Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro

Kheansaard

Panichob²,

Fucharoen³

et al. 2011

Acta Haematol

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Background/Aim: β-Thalassemia/hemoglobin E (β-thal/HbE) is a common hereditary anemia in Thailand. Ineffective erythropoiesis due to apoptosis and decreased lifespan of circulating thalassemic red blood cells are the major causes of anemia. Changes to bone marrow microenvironment could contribute to apoptotic events. This study examined the effects of cytokines interleukin-1β, tumor necrosis factor-α and interferon-γ on apoptosis of β-thal/HbE erythroid progenitor cells in vitro, including nitric oxide-mediated apoptotic processes. Methods: Percent apoptosis of erythroid progenitor cells from 5 β-thal/HbE patients and 5 normal control subjects was examined using flow cytometry. In addition, the inducible nitric oxide synthase (iNOS) mRNA level and nitrite production were measured using quantitative PCR and the Griess method, respectively. Results: Upon cytokine treatment, a higher percent apoptosis was obtained with β-thal/HbE erythroid progenitor cells compared with control, and the maximum effect was observed using 20 ng/ml interferon-γ on day 14 of culture. There was an increase in iNOS mRNA level and a concomitant elevation of nitrite concentration in culture medium. Apoptosis and nitrite level were abrogated when β-thal/HbE and control cells were treated with S-methylisothiourea sulfate, an iNOS inhibitor. Conclusion: The marked sensitivity of erythroid progenitor cells from β-thal/HbE patients to cytokine-induced apoptosis via an NO-mediated process reflects a proapoptotic status of such thalassemic red blood cells.

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“…Serum levels of aspartate aminotransaminase and alanine aminotransaminase were slightly increased, and 1 patient had positive serology for HCV, all likely from previous multiple blood transfusions. Serum lactate dehydrogenase levels were not much elevated, likely from an ineffective erythropoiesis [10] and hemolysis. All except 5 patients had normal serum high-sensitivity C-reactive protein levels.…”

Section: Tablementioning

confidence: 99%

Pulmonary Artery Pressure Correlates Directly with Spleen Volume in Non-Splenectomized Hemoglobin E/β-Thalassemia Patients

Atichartakarn

Chuncharunee²,

Yamwong³

et al. 2013

Acta Haematol

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A mechanism of ineffective erythropoiesis in -thalassemia/Hb E disease

Abstract: These results suggest the failure of thalassemic erythroblasts to cope with cellular stress caused by an impaired UPR function as a result of high Ca(2+) levels may exacerbate thalassemic cell death during erythropoiesis.

Cited by 33 publications

References 30 publications

Pulmonary Hypertension Risk in Patients with Hemoglobin H Disease: Low Incidence and Absence of Correlation with Splenectomy

Pulmonary Hypertension Risk in Patients with Hemoglobin H Disease: Low Incidence and Absence of Correlation with Splenectomy

Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro

Pulmonary Artery Pressure Correlates Directly with Spleen Volume in Non-Splenectomized Hemoglobin E/β-Thalassemia Patients

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