The effect of fetal hemoglobin on the survival characteristics of sickle cells

Franco, Robert S.; Yasin, Zahida; Palascak, Mary B.; Ciraolo, Peter; Joiner, Clinton H.; Rucknagel, Donald L.

doi:10.1182/blood-2005-09-008318

Cited by 107 publications

(103 citation statements)

References 16 publications

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“…Hemolytic rate in SCD has been measured directly by labeled-erythrocyte survival studies (34,41). More often, indirect surrogates of red cell lifespan, including plasma hemoglobin, total hemoglobin, erythrocyte microparticles, serum bilirubin, reticulocyte count, lactate dehydrogenase (LDH), alanine aminotransferase (AST), and urine hemosiderin or cell-free hemoglobin, have been used singly and in combination to estimate the hemolysis intensity (20,25).…”

Section: Elevated Trv and Scd Complicationsmentioning

confidence: 99%

“…HbF has its most robust effects on subphenotypes associated with sickle vaso-occlusion, including ACS (30)(31)(32). Failure of HbF to afford similar levels of protection for hemolysis-associated subphenotypes might be a consequence of insufficient HbF in some cells, which allows continued intravascular hemolysis and endothelial injury over long exposures (33,34).…”

Section: Introductionmentioning

confidence: 99%

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Intravascular hemolysis and the pathophysiology of sickle cell disease

Kato¹,

Steinberg²,

Gladwin³

2017

Journal of Clinical Investigation

521

444

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Section: Elevated Trv and Scd Complicationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intravascular hemolysis and the pathophysiology of sickle cell disease

Kato¹,

Steinberg²,

Gladwin³

2017

Journal of Clinical Investigation

521

444

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“…For selected postinfusion time points, labeled RBCs were isolated by streptavidin-coated magnetic beads (Dynal Biotech, Lake Success, NY) as previously described 40 and the HbA1c content determined by HPLC. 41 Parallel studies were also performed using another source of magnetic beads (Miltenyi Biotec) that gave very similar results (not shown).…”

Section: Time Course Of B-rbc Hba1cmentioning

confidence: 99%

Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c

Cohen

Franco²,

Khera

et al. 2008

Blood

Self Cite

389

370

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Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls.

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“…HU inhibits the enzyme ribonucleotide reductase (RNR), causes cell-cycle arrest, and allows globin genes to be more actively expressed. By killing cycling cells, HU changes the kinetics of erythroid proliferation, forcing more F cells to be produced from primitive progenitors and directly stimulating HbF production (Franco et al, 2006).Furthermore, HU therapy increases haemoglobin concentration, reduces the expression of adhesion molecules on erythrocytes, platelets and neutrophils, decreases the production of granulocytes and contributes to the improvement of clinical events, reducing the number of hospital admissions, the frequency of painful episodes, the need for transfusion and the occurrence of CVA and ACS (Platt et al, 1984;Steinberg et al, 2003;Zago, Pinto, 2007;Cartron, Elion, 2008;Orah, Platt, 2008;Conran, Franco-Penteado, Costa, 2009;Lou et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

Pedrosa

Barbosa

Santos

et al. 2014

Braz. J. Pharm. Sci.

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Hydroxyurea (HU) is the most important advance in the treatment of sickle cell anaemia (SCA) for preventing complications and improving quality of life for patients. However, some aspects of treatment with HU remain unclear, including their effect on and potential toxicity to other blood cells such as neutrophils. This study used the measurement of Lactate Dehydrogenase (LDH) and Methyl ThiazolTetrazolium (MTT) and the comet assay to investigate the cytotoxicity and damage index (DI) of the DNA in the neutrophils of patients with SCA using HU.In the LDH and MTT assays, a cytoprotective effect was observed in the group of patients treated, as well as an absence of toxicity. When compared to patients without the treatment, the SS group (n=20, 13 women and 07 men, aged 18-69 years), and the group of healthy individuals (AA) used as a control group (n=52, 28 women and 24 men, aged 19-60 years), The SSHU group (n=21, 11 women and 10 men, aged 19-63 years) showed a significant reduction (p<0.001) in LDH activity and an increase in the percentage of viable cells by the MTT (p<0.001). However, the SSHU group presented significantly higher DI values (49.57±6.0 U/A) when compared to the AA group (7.43 ± 0,94U/A) and the SS group (22.73 ±5.58 U/A) (p<0.0001), especially when treated for longer periods (>20 months), demonstrating that despite the cytoprotective effects in terms of cell viability, the use of HU can induce DNA damage in neutrophils.Uniterms: Hydroxyurea/cytotoxicity. Sickle cell anaemia/treatment. Neutrophils/DNA damage. Deoxyribonucleic acid/damage.A hidroxiuréia (HU) constitui o avanço mais importante no tratamento da anemia falciforme (AF) por prevenir complicações e aumentar a qualidade de vida dos pacientes. Entretanto, alguns aspectos do tratamento com HU permanecem obscuros, incluindo a sua ação e potencial toxicidade em outras células sanguíneas, tais como neutrófilos. Este estudo utilizou a mensuração da lactato desidrogenase (LDH) e do metil tiazoltetrazólio (MTT) e o ensaio do cometa para investigar a citotoxicidade e índice de dano (ID) ao DNA em neutrófilos de pacientes com AF em uso do medicamento. Nos ensaios de LDH e MTT, observou-se além de ausência de toxicidade, uma ação citoprotetora no grupo de pacientes tratados, Grupo SSHU (n=21, 11 mulheres e 10 homens, com idades entre 19-63 anos), quando comparados aos pacientes sem tratamento, Grupo SS (n=20, 13 mulheres e 07 homens, 18-69 anos), e grupo de indivíduos saudáveis (AA) usado como controle (n=52, 28 mulheres e 24 homens, 19-60 anos), com redução significativa (p<0,001) na atividade de LDH e aumento no percentual de células viáveis pelo MTT (p<0,001). Entretanto, o grupo SSHU apresentou valores de ID significativamente elevados (49,57±6,0 U/A), quando comparados ao grupo AA (7,43 ± 0,94U/A) e grupo SS (22,73 ±5,58 U/A) (p<0,0001), especialmente quando tratados por períodos mais longos (>20 meses), demonstrando que apesar dos efeitos citoprotetores quanto à viabilidade celular, o uso da HU pode induzir lesão ao DNA de neutrófilos.Unitermo...

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The effect of fetal hemoglobin on the survival characteristics of sickle cells

Abstract: The determinants of sickle red blood cell (RBC) life span have not been welldefined but may include both intrinsic factors (eg, the tendency to sickle) and extrinsic factors (eg, the capacity of the reticuloendothelial system to remove defective RBCs).

Cited by 107 publications

References 16 publications

Intravascular hemolysis and the pathophysiology of sickle cell disease

Intravascular hemolysis and the pathophysiology of sickle cell disease

Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c

Cytotoxicity and DNA damage in the neutrophils of patients with sickle cell anaemia treated with hydroxyurea

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