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![Intravascular hemolysis and NO bioactivity in sickle cell disease. Intravascular hemolysis releases hemoglobin, arginase, and LDH into the plasma. Hemoglobin inactivates NO, generating methemoglobin and inert nitrate. The NO synthases generate NO from the substrate L-arginine. Arginase consumes L-arginine. NO is also consumed by reactions with reactive oxygen species, producing oxygen radicals like peroxynitrite (ONOO-)(C). Decreased NO bioactivity in sickle cell disease is associated with pulmonary hypertension, priapism, leg ulceration, hypertension, and nonhemorrhagic stroke. (From Kato et al.[178].)](publication/23709208/figure/fig1/AS:601671587618836@1520461093365/Intravascular-hemolysis-and-NO-bioactivity-in-sickle-cell-disease-Intravascular.png)
Intravascular hemolysis and NO bioactivity in sickle cell disease. Intravascular hemolysis releases hemoglobin, arginase, and LDH into the plasma. Hemoglobin inactivates NO, generating methemoglobin and inert nitrate. The NO synthases generate NO from the substrate L-arginine. Arginase consumes L-arginine. NO is also consumed by reactions with reactive oxygen species, producing oxygen radicals like peroxynitrite (ONOO-)(C). Decreased NO bioactivity in sickle cell disease is associated with pulmonary hypertension, priapism, leg ulceration, hypertension, and nonhemorrhagic stroke. (From Kato et al.[178].)
Source publication
The root cause of sickle cell disease is a single beta-globin gene mutation coding for the sickle beta-hemoglobin chain. Sickle hemoglobin tetramers polymerize when deoxygenated, damaging the sickle erythrocyte. A multifaceted pathophysiology, triggered by erythrocyte injury induced by the sickle hemoglobin polymer, and encompassing more general ce...
Context in source publication
Context 1
... reacts rapidly with cell-free hemoglobin, producing nitrate, methemoglobin, and iron-nitrosyl hemoglobin. A normal function of NO is to activate soluble guanylate cyclase, which converts GTP to cGMP, relaxing vascular smooth muscle and causing vasodilatation (Fig. 2). The consumption of endothelial NO because of free plasma hemoglobin leads to a state of reduced endothelial NO bioavailability. This impairs the downstream homeostatic vascular functions of NO, such as inhibition of platelet activation, and aggregation and transcriptional repression of the cell adhesion molecules, VCAM- 1(vascular cell adhesion molecule-1), ICAM-1 (intercellular adhesion molecule-1), P-selectin, and E- ...
Citations
... It is characterized by mutation of the β globin gene at position 6 of chromosome number 11 which causes production of rigid β globin chain of a hemoglobin molecule [2]. This leads to less deformable red blood cells (RBCs) during migration process across microvasculature due to formation of sickle shaped RBCs [3]. The hallmark of the pathological process behind major clinical manifestations of SCD are hemolysis and microvascular occlusion [4]. ...
Background
Patients with sickle cell disease (SCD) are prone to iron profile derangements. This study aimed to determine the prevalence of iron deficiency anaemia (IDA) and their predictors among children with SCD aged between 6 months and 14 years. Assessment of the prevalence of IDA and its predictors helps to understand ways of alleviating the magnitude of the problem so as to prevent possible complications such as shortness of breath and chest pain.
Methods
This was a cross-sectional analytical hospital-based study which included 174 patients with SCD attending SCD clinics at St. Gema hospital and Dodoma regional referral hospital in Dodoma city from October 2020 to March 2021. The cut-off points for detection of IDA was serum ferritin level < 30 µg/L and low mean corpuscular volume (MCV) for age. Data were analyzed using SPSS software version 25.0. Multivariate logistic regression analysis was used to determine the predictors of IDA. P-value less than 0.05 was considered significant.
Results
The prevalence of IDA in this study was (16.1%, n = 28). Family income of less than 70,000/= TZS/month (AOR = 2.2, 95% CI = 1.07–2.49, p = 0.023), being transfused with blood less than 3 times from the time of being diagnosed with SCD (AOR = 5.5, 95% CI = 1.03–8.91, p = 0.046), and eating red meat at least once per month (AOR = 3.60, 95% CI = 1.37–9.46, p = 0.010) remained the independent predictors of IDA in multivariate regression analysis.
Conclusion
The findings of this study have shown that, support of families with children suffering from SCD in terms of financial support for improving medical services including optimal blood transfusion and affordability of diet which is rich in iron such as red meat is imperative.
... SCD is the commonest hemoglobinopathy [1] affecting millions of people worldwide and this remains a public health concern. The disease evolved through four periods: the tribal medicine period in Africa [2], clinical recognition by Western medicine, an era of biochemical/molecular characterization [3,4] with Venon Mason and Linus Pauling initiative [5,6], and now an era of molecular therapy [7]. ...
In this review chapter, sickle cell disease (SCD) overview, its diagnostic procedures and markers to date as well as the proposed model or pathways by which SCD oxidative stress activates caspases leading to a shrunken sickle cell are presented. Of the various approaches used to mitigate SCD effects, it is anticipated that the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Caspases could possibly edit the sixth position alteration on the β-globin gene on chromosome 11. Even though CRISPR/ Caspases hold promise in sickle cell disease in the near future, it is also possible for it to create genomic chaos. Here, several schools of thought are presented as well.
... The clinical phenotype of this variant form of sickle cell disease (SCD) is characterized by a chronic hemolytic anemia with multiple cardiac and vascular complications [3,6,7]. The severity of symptoms and the treatment approach can vary, depending on the specific genetic mutations involved [8,9]. There is a lack of studies specifically documenting the phenotype of Sβ-thal patients; in fact, Sβ-thal patients have often been included in studies on homozygous SCD patients, based on a similar clinical course [10]. ...
Cardiac involvement in sickle beta thalassemia (Sβ-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. One-hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sβ-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sβ-thal and SCA patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCA-specific bi-atrial and biventricular reference values.
... Generallyspeaking, the documented prevalence of cholelithiasis in SCD may be related to the selection criteria, age group studied and possibly the diagnostic methods. Nevertheless, the ultrasonographic method has been proven to be a highly sensitive and specific method of diagnosing cholelithiasis [27,30,31,32]. ...
... As reported in many of the previous studies [21,24,28,30,[32][33][34][35]. prevalence of cholelithiasis was observed to increase with age. ...
... 34 This trend can probably be explained by the repeated progressive sickling of the red cells with increasing age leading to deposition of pigment stones in the gall bladder [33,[36][37][38][39]. The influence of puberty on the occurrence of the condition has also been postulated [24,28,30,[32][33][34][35] and this may be a possible explanation for the findings in the present study. The prevalence of cholelithiasis has been reported to be more in females compared to their male counterparts especially in the adult population [21,40,41] and this has also been observed in some paediatric studies [28,30]. ...
Background: Sickle cell disease (SCD) is an autosomal recessive blood disorder with multi-organ manifestations including the gall bladder. Studies have shown that individuals with sickle cell disease have strong tendency of developing pigment gallstones due to chronic red blood cell hemolysis and increased bilirubin levels.
Aim and Objectives: The aim of this study was to evaluate and compare the gallbladder changes which includes volume, wall thickness, presence of biliary sludge and prevalence of calculi between age and sex-matched sickle cell disease patients and apparently healthy, normal non-SCD individuals.
Materials and Methods: This was a cross-sectional comparative study of 50 known SCD patients attending the Haematology clinic of sub-urban tertiary health facility in Nigeria, and equal number of age and sex-matched apparently healthy, non-SCD volunteers attending the Well people clinic of the same hospital as controls. Each subject was evaluated for gallbladder volume, wall thickness, presence of biliary sludge and gallstones using a 3.5-5MHz curvilinear array transducer of a Mindray ultrasound machine, DC-6 model, 2016.
Data Analysis: The data collected was analysed using the IBM Statistical Package for Social Sciences (SPSS) version 21.
Statistical test was considered significant at p-value ≤ 0.05 and a confidence interval of 95%.
Results: Out of the 100 subjects who underwent scanning, 50 were patients with sickle cell disease, consisting of 29 males (58.0%) and 21 females (42.0%), while the remaining 50 were non-sickle cell disease volunteers serving as controls, comprising 24 males (48.0%) and 26 females (52.0%). Their ages ranged from 2 to 65 years.
The mean age of the cases and controls was 22.1±14.7 years and 19.9±12.6 years respectively. Among the patients; 8 (16.0%) had cholecystitis and 10 (20.0%) had gallstones, with no detectable abnormality in the controls.
Conclusion: The ultrasonographic prevalence of gallbladder abnormalities was recorded only in patients with sickle cell disease when compared to apparently healthy controls as shown with increased prevalence with age.
... Genetic causes: A single-base mutation in the sixth codon of the beta-globin chain on chromosome 11 is what causes SCA. This leads to the formation of mutant sickle hemoglobin (HbS) (Hebbel et al., 2012), On chromosome 11, this mutation causes valine to replace glutamic acid at position six of the beta-globin chain gene (Elnaim et al., 2020), and HbS β-globin chains are substituted for normal HbA β-globin chains (Steinberg, 2008). ...
Sickle cell anemia (SCA) is a known hematological disorder that arises from a single point mutation in codon 6 of the β-globin gene that results in a glutamic acid to valine substitution.This mutation leads to the formation of abnormal hemoglobin called HbS. Homozygous hemoglobin S (HbSS disease) is the most common form of SCD, In addition to homozygous SCD (HbSS), other forms such as HbSC and HbSB thalassemia also exist. This study has been conduct during 3 months between November/2022 and January /2023 in the hereditary blood disease center / Karbala Health Directorate. The total number of participants are (100) person including (35) patients with painful crisis, (35) patients with steady state, and (30) control group, all of the patients and control group were male, in addition, There ages ranged from (3-55).
Patients and healthy individuals provided venous blood samples totaling 5 ml. Each person also provided personal information, including their age, height, and weight. visfatin, and vcam-1 were done by manual kit with Enzyme-linked ImmunoSorbent Assay , while ferritin, Complete Blood Count, C-Reactive Protein, D-dimer, and Lactate dehydrogenase were done by auto chemistry analyzer.
In this study, we aimed to study the role of VCAM-1 as a marker of endothelial dysfunction in SCA patients. Investigation of the role of visfatin, as a marker of inflammation in SCA patients. Compared the expression of visfatin, sVCAM-1, Ferritin, and D dimer, in SCA patients that to control group. Comparing the severity of these markers D dimer, Ferritin, visfatin, and sVCAM-1 in children and adults. Evaluate the association between serum visfatin, sVCAM-1 level in SCA patients, and the frequency of vaso-occlusive crises. Possible usage of these markers as a
X
predictive index for VOC occurrence. Study correlations among visfatin, sVCAM-1, Ferritin, and D dimer markers with different hemolysis and inflammation markers.
The results showed there has been significant differences in concentrations of D dimer, Ferritin, visfatin, CRP, HCT, sVCAM-1, LDH, HB, WBC, RBC, and Retic count, in SCA patient (painful crisis, steady state) in comparison with the control group for both adults and children. Also observed no significant differences in MCH levels between SCA patients and the control group for both adults and children.
The results of MCHC showed that there were significant differences between patients with sickle cell anemia and healthy people, in children only. While in adults there are no significant differences between patients and healthy.
The results also showed that there were significant differences in platelet, and MCV levels between patients with sickle cell anemia and healthy subjects, in adults only, but in children, there were no significant differences between patients with sickle cell anemia and healthy group.
In this study, SCA patients with the painful crisis have significant correlations between (visfatin, LDH), and (visfatin, Ferritin).
... Congenital penile pathologies: hypospadias [1,[20][21][22][23][24][25], chordee [26], epispadias [27], phimosis [28][29][30], and micropenis [31,32]. Acquired penile pathologies: Peyronie's disease [33,34], stenosis [6,8], lymphoedema [35][36][37], priapism [36][37][38][39][40], penile fracture [37], and buried penis [30]. ...
The penis is a complex organ with a development cycle from the fetal stage to puberty. In addition, it may suffer from either congenital or acquired anomalies. Penile surgical reconstruction has been the center of interest for many researchers but is still challenging due to the complexity of its anatomy and functionality. In this review, penile anatomy, pathologies, and current treatments are described, including surgical techniques and tissue engineering approaches. The self-assembly technique currently applied is emphasized since it is considered promising for an adequate tissue-engineered penile reconstructed substitute.
... Deoxygenated sickle hemoglobin polymerizes, resulting in erythrocyte deformation, hemolysis, anemia, vaso-occlusive episodes, end-organ injury, and a decreased life expectancy [3]. In addition, SCD is associated with multiple alternative mutations of the -hemoglobin gene, which are known as sickle cell anemia, sickle cell trait, HbSC disease, HbSE disease, -thalassemia, etc. [4]. ...
Sickle cell disease (SCD) is an influential genetic disorder on a global scale. The sickle cell population has been a large collective in recent years. Vaso-occlusion, membrane injury, and cardiovascular complications were discovered to result from its presence. There is currently no treatment that can completely cure SCD. Using a method of literature review, this paper discusses the history, pathology, and potential treatments. A point mutation of the sixth amino acid in the -hemoglobin gene (HBB) is the genetic etiology of sickle cell disease. The replacement of glutamic acid with valine reduces the oxygen-carrying capacity of erythroid. Even though the cause of SCD is evident, the treatments, including blood transfusion, hydroxyurea, gene-editing, and GBT440 agent therapy, are still uncertain. Further research and testing are required to reduce the morbidity of SCD, and additional efforts are required to increase the rate of SCD cure.
... Patients affected by SCD have overall higher lifetime risk of morbidities and earlier mortalities than their heterozygous counterparts with SCT. 1,2 HbS polymerizes and damages the erythrocyte membrane under conditions of hypoxia and intracellular dehydration. Sickle-shaped erythrocytes increase blood viscosity within the microvasculature, which can lead to microcirculatory collapse and, in free-tissue transfer patients, partial flap necrosis. ...
Free-tissue transfer reconstruction in patients with sickle cell anemia risks failure due to polymerization of sickle hemoglobin within the flap microcirculation. However, outcomes vary, as the amount of polymerization is dependent on factors such as disease phenotype/diagnosis, degree of hypoxia, and intracellular dehydration. Most of the literature focuses on patients with sickle cell disease, which produces higher concentrations of sickle hemoglobin and, therefore, is a contraindication to microvascular reconstruction. Fewer reports describe microsurgery in patients with sickle cell trait (SCT) who carry the heterozygous phenotype. Here, we present a case in which a patient with SCT underwent microsurgical breast reconstruction with deep inferior epigastric perforator free-tissue transfer. The 52-year-old woman had previously experienced a failed alloplastic-based reconstruction after radiation therapy for breast cancer. In our case, clinical and Doppler examinations demonstrated that arterial and venous anastomoses had remained patent; so the patient was discharged on postoperative day 4. Blistering developed on postoperative day 8, and by day 15 there was partial necrosis of the inferior-lateral aspect of the deep inferior epigastric perforator flap. Debridement and closure resolved the issue, and at 5 months postprocedure, the flap remained well-perfused and well-incorporated. This case, presented here with patient consent, reports a successful outcome of microsurgical reconstruction in a patient with SCT. It expands the limited evidence to support the safety and feasibility of autologous surgical interventions for patients with the heterozygous phenotype of sickle cell anemia.
... ng/dL) in male and ( 4.81±0.85 ng/dL) in female as clarified in table(6). ...
The hereditary hemoglobinopathy known as sickle cell disease is characterized by abnormal hemoglobin synthesis, hemolytic anemia, and intermittent obstruction of tiny blood arteries. The current investigation aims to study the relationship between interferon-gamma gene expression and serum levels with thyroid hormone status and Ferritin levels in sickle cell anemia patients. Blood samples were collected from 50 patients suffering from SCA and 50 healthy volunteers as a control group. The results of the relation of IFN-γ serum level with T3, T4 and TSH levels showed a positive relationship between IFN-γ serum and TSH levels. At the same time, an inverse association to T3 and T4 levels with high significance also showed high IFN-γ gene expression (10.78 ±5.06 Fold) in the patient group as compared with control (2.079 ±0.52 Fold) at a significant difference, as well as the results found acquire strong positive association between IFN-γ serum level and IFN-γ mRNA expression in the patient group compared with the control group. The current study concluded that there was an inverse association among T3, T4 and IFN-γ serum with high significance, as high gene expression of IFN-γ, and a strong positive association between IFN-γ serum level and IFN-γ mRNA expression. Keywords: IFN-γ, SCA, Ferritin, TSH, T3, T4.
... The sickle gene is a point mutation in the beta globin gene on exon 1 resulting in a change from GAG to GTG (2). The resulting sickle haemoglobin has replaced glutamic acid with valine at position 6 of the beta globin polypeptide (3). The sickle haemoglobin f o r m s p o l y m e r s u n d e r c o n d i t i o n s o f deoxygenation. ...
