Pattern of AST and ALT changes in Relation to Hemolysis in sickle cell Disease

2011 ◽  
Vol 4 ◽  
pp. CMBD.S3969 ◽  
Author(s):  
K. Nsiah ◽  
V.P. Dzogbefia ◽  
D. Ansong ◽  
A. Osei Akoto ◽  
H. Boateng ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Multivariate Regression ◽  
Alanine Transaminase ◽  
Hemoglobin Level ◽  
Inverse Association ◽  
Regression Analyses ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Serum Aminotransferase

Background Elevated aminotransferase levels are commonly associated with compromised hepatic integrity from various insults. In sickle cell disease, aspartate transaminase (AST) is also released via intravascular hemolysis. This study was done to determine the pattern of changes in AST and alanine transaminase (ALT), in particular the AST:ALT ratio, and to relate these to the hemolytic state, which we consider to be more important than hepatic and cardiac dysfunction in some individuals with sickle cell disease. Methods Serum aminotransferase levels were measured in 330 subjects with sickle cell disease, as well as hemoglobin, reticulocytes, and lactate dehydrogenase. The AST:ALT ratio was designated as a hemolytic marker, and simple and multivariate regression analyses were carried out between this ratio and other hemolytic markers. Results Mean AST and ALT levels were 48.24 % 27.78 and 26.48 % 22.73 U/L, respectively. However, for 49 subjects without sickle cell disease, mean AST and ALT levels were the same, ie, 23.0 U/L. In the subjects with sickle cell disease, the increases in AST levels were far higher than for ALT, supporting its release via intravascular hemolysis. In 95.8% of the subjects with sickle cell disease, the AST:ALT ratio was > 1, but our results did not suggest overt malfunctioning of the liver and heart in the majority of subjects. Conclusion Regression analyses support the use of the AST:ALT ratio as a hemolytic marker, because it has an inverse association with the hemoglobin level. Whether in steady state or in crisis, provided hepatic and cardiac integrity has not been compromised, subjects with sickle cell disease would have higher AST levels due to the hemolytic nature of the condition. This is the first report highlighting the AST:ALT ratio in sickle cell disease.

Abstract 65: Anemia-related Heart Failure in Sub-saharan African Sickle Cell Disease Patients

2017 ◽  
Vol 121 (suppl_1) ◽  
Author(s):  
Adebayo C Atanda ◽  
Yahya Aliyu ◽  
Oluwafunmilayo Atanda ◽  
Aliyu Babadoko ◽  
Aisha Suleiman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Hemoglobin Level ◽  
Sub Saharan Africa ◽  
Cell Disease ◽  
Jet Velocity ◽  
Sub Saharan

Introduction: Anemia has been implicated in heart failure. Existing literatures, involving predominantly African-Americans, suggests that Sickle Cell Disease (SCD) maybe linked to various cardiovascular complications including pulmonary hypertension and left venticular dysfunction. Peculiarly, our study involves exclusively Sub-Saharan population. Method: We conducted a cross sectional observational study of 208 hydroxyurea-naive consecutive SCD patients aged 10-52 years at steady state and 94 healthy non-matched controls who were studied in an out patient clinic in Sub-Saharan Africa. SCD patients were required to have electrophoretic or liquid chromatography documentation of major sickling phenotypes. Control group was required to have non-sickling phenotypes. Cardiac measurements were performed with TransThoracic Echo according to American Society of Echocardiography guidelines. Hemoglobin level was also obtained. Results: Hemoglobin level in SCD group (8.5+/- 1.5) was significant (P<0.001) compared to control (13.8+/- 1.7). Although SCD group had significantly higher values of left ventricular (LV) size, there was no qualitative evidence of LV dysfunction. SCD group had higher values of Ejection Fraction but not statistically significant. There was no evidence of LV wall stiffening to impair proper filling in SCD group, with the ratio of early to late ventricular filling velocities, E/A ratio elevated (1.7+/-0.4 compared to 1.6+/- 0.4; P=0.010). Right ventricular systolic pressure was determined using the formula of 4x Tricuspid Reugurgitant jet (TRV) square as an indirect measurement of Pulmonary arterial systolic pressure. SCD patients had significantly higher mean±SD values for tricuspid regurgitant jet velocity than did the controls (2.1±0.6 vs. 1.8±0.5; p= 0.001). Within the SCD group, there was no clear pattern of worsening diastolic function with increased TRV. Furthermore, E/A had a significant positive relationship with jet velocity in bivariate analysis (R=0.20; P=0.013). Conclusions: We were unable to demonstrate existence of anemia-associated left ventricular dysfunction in Sub-Saharan African with SCD. Further studies is required to highlight the reason behind this finding.

Arginine Metabolite Profiling in Sickle Cell Disease: Abnormal Levels and Correlations with Pulmonary Hypertension, Desaturation, Hemolysis and Organ Dysfunction.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1205-1205
Author(s):  
Gregory J. Kato ◽  
Wang Zeneng ◽  
James G. Taylor ◽  
Roberto F. Machado ◽  
William C. Blackwelder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Renal Dysfunction ◽  
Sickle Cell ◽  
Early Mortality ◽  
Systemic Hypertension ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Arginine Transport

Abstract Pulmonary arterial hypertension (PAH) in patients with sickle cell disease (SCD) is linked to intravascular hemolysis, renal dysfunction, systolic hypertension, cholestasis, and early mortality. Although the pathophysiology of PAH in SCD is multifactorial, one important and fundamental factor is impaired nitric oxide bioavailability. Severe intravascular hemolysis releases hemoglobin and arginase into blood plasma, leading to consumption of nitric oxide and its plasma precursor L-arginine, the obligate substrate for the nitric oxide synthases (NOS). In order to explore other potential alterations in the arginine pathway that might affect arginine bioavailability and nitric oxide production, we used high-performance liquid chromatography-tandem mass spectrometry to determine the plasma concentrations for several key metabolites that may affect NOS activity or arginine transport: asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), N-monomethyl-L-arginine (MMA), and N-ω-hydroxy-L-arginine (NOHA). Plasma levels of ADMA, SDMA and MMA are significantly higher in all forms of SCD than in healthy African American control subjects (Table 1). NOHA, the intermediate species in nitric oxide synthesis from L-arginine, is significantly lower in sickle-β-thalassemia (Sβ-thal) patients and homozygous SCD (SS). L-arginine levels are significantly lower in all forms of SCD, as previously reported. PAH as assessed by echocardiography screening was correlated to SDMA (r=0.30, p&lt;0.0001) and NOHA (r=0.23, p=0.002). Similar correlations were observed to NT-proBNP, another marker of PAH. Low oxygen saturations were linked to high levels of all four arginine metabolites. ADMA levels were elevated with severe hemolysis, and unexpectedly lower with renal dysfunction. Levels of SDMA and NOHA were significantly related to renal dysfunction (p&lt;0.01), with an additional link of NOHA to systemic hypertension (p&lt;0.001). In addition, Cox proportional hazard analysis showed a relationship of the arginine/SDMA ratio to early mortality (p&lt;0.001). In summary, levels of the endogenous NOS inhibitor ADMA are highly elevated in SCD and linked to hemolysis, and may contribute to hemolysis-associated endothelial dysfunction. The levels of SDMA, a competitive inhibitor of arginine transport and intracellular bioavailability, are also elevated and linked to PAH, desaturation, renal dysfunction and early mortality risk. The low levels of arginine and NOHA in SCD are consistent with low substrate availability for NOS, and may also limit NO production. The role of arginine metabolites in dysregulation of the arginine-nitric oxide axis and pulmonary hypertension in SCD merits further investigation. Table 1. Arginine Metabolites in Sickle Cell Disease compared to controls. Metabolite Control (n=29) SC (n=34) Sβ-thal (n=11) SS (n=130) Values indicate median values in μM. *p&lt;0.05; **p&lt;0.01; ***p&lt;0.001, Mann-Whitney test compared to controls. ADMA 0.31 0.82*** 0.92* 0.99*** SDMA 0.83 0.92* 1.03** 1.03*** MMA 0.13 0.15* 0.20** 0.18*** NOHA 2.50 2.23 2.15* 1.80** L-Arginine 78.3 51.5*** 41.6*** 45.5***

Heme Induces Endothelial Tissue Factor Expression: Potential Role in Hemostatic Activation in Patients with Intravascular Hemolysis Including Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1902-1902
Author(s):  
Yamaja Setty ◽  
Suhita Gayen Betal ◽  
Jie Zhang ◽  
Nigel S Key ◽  
Marie Stuart
Keyword(s):  
Flow Cytometry ◽  
Endothelial Cells ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Whole Blood ◽  
Dependent Manner ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Tnf Α ◽  
Endothelial Tissue

Abstract Plasma levels of heme in the 20 to 600 μM range are found in clinical conditions associated with intravascular hemolysis including paroxysmal nocturnal hemoglobinuria and sickle cell disease, conditions also associated with a thrombotic tendency. Objectives: To investigate whether heme, an inflammatory mediator and a product of intravascular hemolysis in patients with hemolytic anemia including sickle cell disease (SCD), could modulate hemostasis by an effect on endothelial tissue factor (TF) expression. Additionally, in SCD patient-related studies, we assessed whether any association existed between whole blood TF activity (WBTF) and levels of surrogate markers of intra-vascular hemolysis including lactate dehydrogenase (LDH) and reticulocyte counts. Methods: Following incubation of human endothelial cells (from umbilical vein and/or lung microvasculature) with heme (1 to 100 μM) for various times (30 minutes to 8 hours), levels of TF protein were assessed using ELISA, flow cytometry and/or Western blotting; and TF mRNA by a semi-quantitative RT-PCR. An assay for TF functional activity was performed using a chromogenic tenase activity kit where specificity of TF activity was tested in antibody-blocking experiments. Three TF-specific antibodies including a rabbit polyclonal and two mouse monoclonal (clones hTF-1 and TF9-10H10) antibodies were used in assays involving TF protein analysis. All experiments were performed in media containing polymyxin B to neutralize any potential endotoxin contamination. In patient-related studies, 81 subjects with SCD (1 to 21 years) were evaluated for levels of WBTF, LDH, and reticulocyte counts and data analyzed for potential relationships. Results: Heme induced TF protein expression on the surface of both macro- and micro-vascular endothelial cells in a concentration-dependent manner with 12- to 50-fold induction noted (ELISA assays) between 1 and 100 μM heme (P&lt;0.05, n=3 to 6). Complementary flow cytometry studies showed that the heme-mediated endothelial TF expression was quantitatively similar to that induced by the cytokine TNF-α. Heme also up-regulated endothelial expression of TF mRNA (8- to 26-fold, peak expression at 2 hours postagonist treatment), protein (20- to 39-fold, peak expression at 4 hours) and procoagulant activity (5- to 13-fold, peak activity at 4 hours post-agonist treatment) in a time-dependent manner. Time-course of heme-mediated TF antigen expression paralleled induction of procoagulant activity with antibody blocking studies demonstrating specificity for TF protein. Potential involvement of endogenously released cytokines including IL-1α and TNF-α in mediating the heme effect was next explored. We found that the latter cytokines are not involved, since antibodies against IL-1α and TNF-α, and an IL-1- receptor antagonist failed to block heme-induced endothelial TF expression. Inhibition of heme-induced TF mRNA expression by sulfasalazine and curcumin suggested that the transcription factor NFκB was involved in mediating heme-induced effect. In patient-related studies, whole blood TF levels in SCD correlated positively with both LDH (r=0.72, p&lt;0.000001), and reticulocyte count (r=0.60, p&lt;0.000001). Conclusions: Our findings demonstrate that heme induces TF expression in endothelial cells, and that the observed effects occurred at patho-physiologically relevant heme concentrations. Our results suggest that heme-induced endothelial TF expression may provide a pathophysiologic link between the intravascular hemolytic milieu and the hemostatic perturbations previously noted in patients with hemolytic anemia including sickle cell disease.

Red Blood Cell Exchange Transfusion, An Underutilized Effective and Reliable Therapeutic Modality in Sickle Cell Disease, Reduces Number of Admissions and Length of Hospital Stay

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4822-4822
Author(s):  
Aref Agheli ◽  
Kirshma Khemani ◽  
Madhumati Kalavar ◽  
William Steier ◽  
Zili He
Keyword(s):  
Sickle Cell Disease ◽  
Hospital Stay ◽  
Sickle Cell ◽  
Blood Viscosity ◽  
Exchange Transfusion ◽  
Hemoglobin Level ◽  
Therapeutic Modality ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
One Year

Abstract Background: The pathophysiology of sickle cell disease (SCD) is based on increased blood viscosity due to abnormal red blood cells (RBCs), which causes SCD complications, such as chronic hemolytic anemia, vaso-occlusive crisis with tissue hypoxemia, and organ dysfunction. Effective treatment of Sickle Cell Anemia is to reduce the blood concentration of Hemoglobin S (Hb S) RBCs. Exchange transfusion (ET) remains an effective but possibly underutilized therapy for the management of various acute and chronic complications of SCD such as acute chest syndrome, thromboembolic stroke, splenic and hepatic infarction, right upper quadrant syndrome, multi-organ failure syndrome, or in preparation for surgery by reducing HbS to less than 30%. RBC ET quickly replaces abnormal RBCs with normal RBCs, thus improving oxygen transport while reducing overall blood viscosity. Methodology: To determine the effectiveness of ET in SCD in reducing the total number of admissions and total in-hospital Length of Stay (LOS) in patients, admitted with any of acute complications of SCD, we retrospectively reviewed the medical records of 38 patients between June 15, 2007 and June 15, 2008. The eligibility criteria were age above 18 years old and admission to the hospital for any SCD complication. Nineteen patients had ET with Hb A containing RBCs, generally with an average packed RBC exchange volume of 70–80 ml/kg patient’s weight. Nineteen patients were treated with conventional managements. Three patients were excluded from the ET group because of prolonged LOS due to non-SCD- related complications. Four patients in the non-Exchange group signed against medical advice on the first day of admission and were excluded from analysis. Results: Sixteen (42.1%) patients were male and 22 (57.9%) patients were female. Their ages ranged from 19 to 67 years old, mean (SD) 30.2 (10.8). Of eligible patients, 19 (50%) patients received at least one therapeutic ET during the one year period of the study. In an independent-Samples T test analysis, the mean (SD) LOS were 7.5 (0.6) and 4.2 (0.6) days for the groups without ET and with ET respectively (95% CI = −5.2 to 1.5, p=.0011) (Figure 1). In this small studied group, this resulted average 3.3 days shorter in-hospital stay in ET group, could have saved 62 in-hospital days in the group who received conventional treatments. This number could have been easily much greater, since our hospital’s electronically stored data revealed that during year 2007, there had been 278 SCD admissions in all age groups. There was no mortality in the ET group, nor were any transfusion-related complications reported. In another analysis of one year follow up data, the number of admissions for the patients who never received ET ranged from 1 to 14, mean (SD) 1.7 (2.3) times in year 2007, while in patients who received at least one ET, the number of following admissions ranged from 0 to 2, mean (SD) 0.7 (1.3) times during the next year (95% CI = 0.16 to 1.7, p= .020). Hemoglobin level of patients in conventional treatment group on the day of discharge ranged from 6.5 to 10.7, mean (SD) 8.9 (1.9) and in ET group it ranged from 8.4 to 12.4, mean (SD) 10.2 (1.2) gr/dl (p= .045). Conclusion: Patients with SCD are frequently admitted to hospital for vaso-occlusive crisis and other complications. Exchange transfusion is a reliable, safe, and effective therapeutic modality in SCD patients, in particular during a catastrophic event. ET can significantly reduce the number of hospital admissions and in-hospital stay days in these patients. In addition, patients managed with ET have a better hemoglobin level on discharge. Figure Figure

Extracellular Hemin Auto-Amplification Intensifies Tissue Injury In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 972-972
Author(s):  
Samit Ghosh ◽  
Solomon F. Ofori-Acquah
Keyword(s):  
Sickle Cell Disease ◽  
Oxygen Saturation ◽  
Organ Failure ◽  
Sickle Cell ◽  
De Novo ◽  
Tissue Injury ◽  
Time Interval ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Breath Rate

Abstract Acute organ failure is a major clinical concern in sickle cell disease (SCD). However, the mechanism responsible for this potentially lethal complication is poorly understood. We tested the hypothesis that extracellular hemin liberates an intracellular danger molecule that promotes acute organ failure in SCD. Transgenic homozygous SCD (SS), sickle-trait (AS) and normal human hemoglobin (Hb) AA mice were infused with purified hemin (35 µmoles/kg), which raised total plasma hemin by ∼0.45 mM (equivalent to 0.72 g/dl Hb) within 5 min in all three groups of mice. In agreement with our previous results, SS but not AA and AS mice (n= 6 for each genotype) developed cardiopulmonary depression at 30 min evident by reductions in oxygen saturation (99.88±0.23% to 92.1±1.3%, p<0.001), breath rate (175.4±20.6 to 77.36±2.25, p<0.001, breath per min), heart rate (574.5±22.7 to 361.9±23.25 beats per min, p<0.001) and pulse distension (512.8±18.7 to 238.8±17.6 µm, p<0.001), and ∼70% of these animals died within 2 hours. Markedly raised lung wet/dry weight ratio in SS mice that succumbed to hemin suggests that the cardiopulmonary depression was secondary to a severe pulmonary edema. To identify biological correlates for the acute adverse effects in the SS mice, cohorts of both sickle and control mice were challenged with the same dose of hemin, blood samples were drawn at baseline (i.e. time=0 min), and 5 and 30 min after the hemin infusion and analyzed for markers of oxidative stress, tissue damage, plasma scavengers and high mobility group box-1 (HMGB-1), a prototypical danger molecule. Plasma hemopexin decreased by ∼80% at 5 min compared to baseline values in all three groups of mice regardless of the Hb genotype. The catabolism of hemopexin was associated with clearance of ∼50% of the hemin infusion from the circulation of AS and AA mice at 30 min. Paradoxically, the plasma concentration of hemin in the SS mice during this same time interval increased by ∼0.2 mM (p<0.001, n=6). The magnitude of this increase was dependent on the dose of hemin administered exogenously. We discovered that the de novo hemin release in the SS mice was preceded by acute intravascular hemolysis (mean decrease in total Hb: ∼1.4 g/dl, p<0.001, n=9, mean increase in cell-free Hb: 1.0 g/dl, p=0.001, n=9), oxidation of oxyHbS to metHbS (mean increase: 12%, p<0.001, n=6) and persistence of metHbS. It is noteworthy that de novo hemin release did not occur in AS mice suggesting that this phenomenon is dominantly influenced by sickle erythrocytes and not by the presence of intracellular HbS per se. Auto-amplification of hemin may help to explain an observation made nearly fifty years ago that SCD patient plasma contains more hemin than the plasma of patients with more severe intravascular hemolysis involving normal adult Hb (e.g. paroxysmal nocturnal hemoglobinuria), who have higher plasma Hb. To determine whether this phenomenon is critical to the cardiopulmonary depression in the SS mice, recombinant human hemopexin was administered 5 min after the infusion to sequester the endogenous hemin release. In hemin challenged SS mice with respiratory distress, intravenous recombinant human hemopexin rapidly halted the decline in oxygen saturation and breath rate and averted inevitable respiratory failure. In conclusion, we have identified a phenomenon of extracellular hemin auto-amplification that appears to be unique to SCD, and may play a critical role in propagating tissue injury in this disorder. Factors that inhibit erythrocyte lysis and accelerate metHb reduction may help to limit extracellular hemin amplification and preserve organ function during episodes of acute exacerbations in SCD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cardiopulmonary Complications of Sickle Cell Disease: Role of Nitric Oxide and Hemolytic Anemia

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Mark T. Gladwin ◽  
Gregory J. Kato
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Iron Chelation ◽  
Cell Disease ◽  
Intravascular Hemolysis ◽  
Inflammatory Stress ◽  
Risk Of Death ◽  
Cardiopulmonary Complications

Abstract Medical advances in the management of patients with sickle cell disease, thalassemia, and other hemolytic anemias have led to significant increases in life expectancy. Improved public health, neonatal screening, parental and patient education, advances in red cell transfusion medicine, iron chelation therapy, penicillin prophylaxis for children, pneumococcal immunization, and hydroxyurea therapy have all likely contributed to this effect on longevity.1,2 Importantly, as a generation of patients with sickle cell disease and thalassemia ages, new chronic complications of these hemoglobinopathies develop. In this context, pulmonary hypertension is emerging as one of the leading causes of morbidity and mortality in adult sickle cell and thalassemia patients, and likely in patients with other hemolytic anemias. A common feature of both sickle cell disease and thalassemia is intravascular hemolysis and chronic anemia. Recent data suggest that chronic intravascular hemolysis is associated with a state of endothelial dysfunction characterized by reduced nitric oxide (NO) bioavailability, pro-oxidant and pro-inflammatory stress and coagulopathy, leading to vasomotor instability and ultimately producing a proliferative vasculopathy, a hallmark of which is the development of pulmonary hypertension in adulthood.3–5 In conclusion, pulmonary hypertension is common in patients with hereditary hemolytic anemias and is associated with a high risk of death in patients with sickle cell disease. New therapies targeting this vasculopathy and aimed at normalizing the vasodilator:vasoconstrictor balance are discussed.

scholarly journals Association of sickle cell disease with nutritional status among under-five children and mediating role of hemoglobin level: secondary analysis of data from 2018 Nigeria Demographic and Health Survey

2020 ◽  
Author(s):  
Mohammad Redwanul Islam ◽  
Md. Moinuddin ◽  
Ayeda Ahmed ◽  
Syed Moshfiqur Rahman
Keyword(s):  
Sickle Cell Disease ◽  
Nutritional Status ◽  
Sickle Cell ◽  
Hemoglobin Level ◽  
Cell Disease ◽  
Anthropometric Indices ◽  
Under Five ◽  
Under Five Children ◽  
Mediating Role

Abstract Background: Malnutrition continues to affect under-five children in Africa to an overwhelming proportion. The situation is further compounded by the burden of sickle cell disease (SCD). However, association of SCD with stunting, wasting, and underweight in a nationally representative sample of under-five children remains unexplored. We aimed to describe prevalence of undernutrition by sickle cell status, to evaluate its association with growth faltering ascertained with anthropometric indices, and to explore mediating role of hemoglobin.Methods: We availed data from the 2018 Nigeria Demographic and Health Survey (DHS) and the sample comprised 11233 children aged 6–59 months who were successfully genotyped for SCD. The DHS employed a two-stage stratified sampling strategy. SickleSCAN rapid diagnostic test was used for SCD genotyping. Z-scores of length/height-for-age (HAZ), weight-for-height (WHZ), and weight-for-age (WAZ) were computed against the 2006 World Health Organization Child Growth Standards. We fitted logistic regression models to evaluate association of SCD with stunting, wasting, and underweight. Mediation analysis was performed to capture the indirect effect of, and proportion of total effect mediated through hemoglobin level in SCD-anthropometric indices association.Results: Prevalences of stunting, wasting, and underweight among children with SCD were 55.4% (54.5–56.4), 9.1% (8.6–9.7), and 38.9% (38.0-39.8), respectively. The odds of stunting were 2.39 times higher (adjusted odds ratio (aOR) 2.39, 95% CI: 1.26–4.54) among sickle children than those with normal hemoglobin. SCD was also significantly associated with underweight (aOR 2.64, 95% CI: 1.25–5.98), but not with wasting (aOR 1.60, 95% CI: 0.85–3.02). Hemoglobin level significantly mediated SCD-HAZ (adjusted indirect effect (aIE) -0.328, 95% CI: -0.387, -0.270), SCD-WHZ (aIE − 0.080, 95% CI: -0.114, -0.050), and WAZ (aIE − 0.245, 95% CI: -0.291, -0.200) associations. The extent of mediation was highest for SCD-HAZ association (adjusted proportion mediated 0.928, 95% CI: 0.535–2.770).Conclusion: We presented compelling evidence of the negative impact of SCD on nutritional status of under-five children. Integration of a nutrition-oriented approach into a definitive SCD care package and its nation-wide implementation could bring promising results by mitigating the nutritional vulnerability of children with SCD.

scholarly journals A Cross Sectional Study of Association of HLA typing with Haemoglobin Level in Sickle Cell Anaemia

2021 ◽  
pp. 523-531
Author(s):  
Raed Alserihi ◽  
Saeed Kabrah ◽  
Hadeel Alsadoun
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Blood Cell ◽  
Sickle Cell ◽  
Blood Groups ◽  
Hemoglobin Level ◽  
Hla Typing ◽  
Control Group ◽  
Allelic Association ◽  
Cell Disease

Background: Sickle-cell Disease (SCD) is the most common blood cell disorder affecting millions of people. In severe cases, regular blood transfusion is an essential practice to relieve clinical symptoms. However, since regular blood transfusion can lead to alloimmunization to foreign human leukocyte antigens (HLA), this may result in severe anemia due to red blood cell destruction. Therefore, this study aimed to determine the association between the hemoglobin level and the presence of HLA genotypes among Sickle Cell Anemia patients.  Methodology: A total of 64 SCD patients and 21 healthy donors seen at King Abdulaziz hospital between November 2019 and February 2021 were recruited for this study. Demographic data including ABO/Rhesus blood groups, hemoglobin concentration, were among the clinical information obtained. HLA genotyping was performed using Polymerase Chain Reaction-Sequence Specific Oligonucleotide (PCR-SSO). The data were cleaned using the Microsoft Excel and analysed using the statistical packages for Social Sciences (SPSS) version 24. Results: The incidence of SCD is not strictly gender-related because of its transmission as an autosomal recessive disorder. Sixty-four individuals (33 females; 31 males) having SCD were analyzed. O blood group recorded the highest prevalence compared to other ABO blood groups in SCD patients. After analysing allelic association, HLA-A*02 was more frequent in SCD patients compared to control. After further allelic combination analysis of patients and compared with the control group, HLA-DQB1*02 was majorly involved in overexpression and decreasing hemoglobin level and significantly different among control and experimental groups. Conclusion: Rhesus-positive blood types were more associated with the SCA. HLA- type II alleles could influence the clinical course of sickle cell disease and HLA-DQB1*02 was significantly different among SCD group and control individuals, which signifies the concept that the allele was overexpressed among patients resulting in low Hb level.

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