Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

Elias, Darcielle Bruna Dias; Rocha, Lilianne Brito da Silva; Cavalcante, Maritza Barbosa; Pedrosa, Alano Martins; Justino, Izabel Cristina Bandeira; Gonçalves, Raquel

doi:10.5581/1516-8484.20120069

Cited by 9 publications

(14 citation statements)

References 29 publications

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“…In the present study there was a significant increase of serum LDH in patients with SCA compared to the control group. These results are in agreement with the study of Elias et al 20 who found a significant increase of LDH compared to a control group in the same study population at steady state. Stojanovic et al 21 found an elevation in serum LDH levels in patients with SCA in both steady state and in crises.…”

Section: Discussionsupporting

confidence: 93%

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

Moreira

Laurentino

Machado

et al. 2015

Revista Brasileira de Hematologia e Hemoterapia

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ObjectiveThis study aimed to evaluate the influence of fetal hemoglobin (Hb F) on hemolysis biomarkers in sickle cell anemia patients.MethodsFifty adult sickle cell anemia patients were included in the study. All patients were taking hydroxyurea for at least six months and were followed at the outpatient clinic of a hospital in Fortaleza, Ceará, Brazil. The control group consisted of 20 hemoglobin AA individuals. The reticulocyte count was performed by an automated methodology, lactate dehydrogenase and uric acid were measured by spectrophotometry and arginase I by enzyme-linked immunosorbent assay (ELISA). The presence of Hb S was detected by high-performance liquid chromatography. The level of significance was set for a p-value <0.05.ResultsA significant increase was observed in the reticulocyte count and lactate dehydrogenase, uric acid and arginase I levels in sickle cell anemia patients compared to the control group (p-value <0.05). Patients having Hb F levels greater than 10% showed a significant decrease in the reticulocyte count, arginase I and lactate dehydrogenase. A significant decrease was observed in arginase I levels in patients taking hydroxyurea at a dose greater than 20 mg/kg/day.ConclusionThe results of this study show that sickle cell anemia patients have increases in the hemolysis biomarkers, lactate dehydrogenase, reticulocyte count, arginase I, uric acid and increases in Hb F can reduce the reticulocyte count and arginase I and lactate dehydrogenase levels.

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Section: Discussionsupporting

confidence: 93%

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

Moreira

Laurentino

Machado

et al. 2015

Revista Brasileira de Hematologia e Hemoterapia

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“…In SCA, concentrations of NO metabolites, such as nitrite, are increased compared with healthy individuals [73]. Several studies show that RBC from SCA patients deplete NO to form its metabolites reducing bioactive NO bioavailability, which may promote vaso-occlusive episodes [73][74][75][76]. Our results are in line with these findings, showing that SS-RBC induced higher levels of nitrite when compared to AA-RBC in PBMC cultures.…”

Section: Discussionsupporting

confidence: 90%

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

et al. 2016

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This study tested the hypothesis that sickle red blood cell (SS-RBC) induce Toll-like receptors (TLR) and Nod-like receptor family, pyrin domain containing 3 (NLRP3)- inflammasome expression in peripheral blood mononuclear cells (PBMC). TLR and NLRP3 inflammasome could contribute to the maintenance of the inflammatory status in sickle cell anemia (SCA) patients, since SS-RBC act as danger signals activating these pathways. In this study, first, we evaluated TLR (2, 4, 5 and 9), NLRP3, Caspase-1, interleukin (IL)-1β and IL-18 expression in PBMC freshly isolated from SCA patients (SS-PBMC) in comparison with PBMC from healthy individuals (AA-PBMC). In the second moment, we investigated whether SS-RBC could interfere with the expression of these molecules in PBMC from healthy donor, in the absence or presence of hydroxyurea (HU) in vitro. TLRs and NLRP3 inflammasome expression were investigated by qPCR. IL-1β, Leukotriene-B4 (LTB4) and nitrite production were measured in PBMC (from healthy donor) culture supernatants. TLR2, TLR4, TLR5, NLRP3 and IL-1β were highly expressed in SS-PBMC when compared to AA-PBMC. Additionally, SS-RBC induced TLR9, NLRP3, Caspase-1, IL-1β and IL-18 expression and induced IL-1β, LTB4 and nitrite production in PBMC cultures. HU did not prevent TLR and NLRP3 inflammasome expression, but increased TLR2 and IL-18 expression and reduced nitrite production. In conclusion, our data suggest that TLR and inflammasome complexes may be key inducers of inflammation in SCA patients, probably through SS-RBC; also, HU does not prevent NLRP3 inflammasome- and TLR-dependent inflammation, indicating the need to develop new therapeutic strategies to SCA patients that act with different mechanisms of those observed for HU.

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“…It was not possible to include a group not being treated with HU because the hospital in which the treatment was performed treats patients with SCA with HU. However, in an earlier study in the same city, but in another hospital, it was possible to determine that the mean nitrite/nitrate level of patients was 25.63 mg/L, which was well below the indices in our study [16].…”

Section: Resultscontrasting

confidence: 74%

Double-Blind Clinical Trial of Arginine Supplementation in the Treatment of Adult Patients with Sickle Cell Anaemia

Eleutério

Nascimento²,

Araújo

et al. 2019

Advances in Hematology

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Background. Sickle cell anaemia (SCA) is the most prevalent monogenic disease in Brazil. In SCA, haemoglobin S (HbS) is formed, which modifies red blood cell morphology. Intravascular haemolysis occurs, in which free Hb and free radicals degrade nitric oxide (NO) and release arginase, which reduces arginine levels. Because arginine is a substrate for NO formation, this decrease leads to reduced NO (vasodilator) synthesis. SCA treatment uses hydroxyurea (HU) to maintain high foetal haemoglobin (HbF) levels and reduces HbS to avoid haemolytic episodes. Objective. To analyse the efficacy of L-arginine as an adjuvant in the treatment of SCA patients. Setting. The State Blood Centre of Ceará, Brazil. Methods. This was a randomized double-blind clinical study of adults with SCA with continuous use of HU at the State Blood Centre of Ceará. The clinical study enrolled 25 patients receiving HU + L-arginine (500 mg) and 25 patients receiving HU + placebo. The treatment was carried out over four months. Laboratory tests were performed to determine the levels of the following: (1) complete blood count; (2) nitrite + nitrate; (3) HbF; and (4) reticulocytes. The clinical experiments were performed by a haematologist. The main outcome measures were nitrite and pain. Results. Statistical analysis showed that the levels of NO were increased in the study group, and there was also a reduction in pain frequency using a pain frequency scale by day, week, and month. The levels of nitrite plus nitrate in the group receiving placebo plus HU did not change among the times evaluated (38.27 ± 17.27 mg/L, 39.49 ± 12.84 mg/L, 34.45 ± 11.25 mg/L, p >0.05), but in the patients who received supplementation with L-arginine plus HU, a significant increase in nitrite plus nitrate levels was observed between M0 and M4 (36.55 ± 20.23 mg/L versus 48.64 ± 20.63 mg/L, p =0.001) and M2 and M4 (35.71 ± 15.11 mg/L versus 48.64 ± 20.63 mg/L, p <0.001). It is important to note that the increase in nitrite plus nitrate levels occurred only in the fourth month of follow-up of patients in the treatment group, showing that at least 4 months of supplementation with L-arginine is necessary to show an increase in these metabolites in the serum. Conclusion. The use of L-arginine as a coadjuvant in the treatment of sickle cell anaemia may function as a potential tool for pain relief, consequently improving the life of patients.

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Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

Cited by 9 publications

References 29 publications

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

Pattern of hemolysis parameters and association with fetal hemoglobin in sickle cell anemia patients in steady state

Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell

Double-Blind Clinical Trial of Arginine Supplementation in the Treatment of Adult Patients with Sickle Cell Anaemia

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