Production Of Abnormal Hemoglobin Research Articles

Pretransfusion Hemoglobin F Level in Thalassemia Patients: Effect of Well-Balanced Versus Poor Transfusion

Background: Thalassemia is a common condition in Iraq. More than ten thousand patients registered in Iraq. If well-balanced hypertransfusion regimen to maintain pretransfusion hemoglobin level above the internationally agreed 9.0 gm/ dL could suppress the patients‘ bone marrow and shutdown the hematopoiesis to the extent of not producing any hemoglobin F. Patients and Methods: One hundred well-balanced transfusion-dependant thalassemia patients were evaluated for Hemoglobin F level prior to their scheduled transfusions. Hemoglobin level must have been more than 9.0 gm/ dL to qualify the patient to be entered into this group. All such patients must have showed minimal skeletal changes of thalassemia. Another hundred patients with frank features of thalassemia and poor history of blood transfusion were also enrolled in the study. We aimed at knowing whether HbF is significantly different in the two groups. It could indicate that patients‘ bone marrow could be totally turned off and no abnormal hemoglobin will be allowed to be produced. Results: Seventy nine percent of our enrolled transfusion-dependent thalassemia patients who fulfilled the criteria and were well managed showed correction of their HbF level to near zero! Thirty five percent of the poorly transfused patients also corrected their abnormal HbF level. Conclusions: This study showed that marrow micromilieu could be manipulated in patients with thalassemia in such a way so as to totally shutdown production of abnormal hemoglobin F as a result of provision of normal hemoglobin through blood transfusion. The fact that even one third of poorly transfused patients could show the same results indicates that any degree of transfusion support will have its impact on the marrow.

A case of severe multi-system disease in a sickle cell SC patient caused by parvovirus B19 infection

Sickle Cell Disease (SCD) is an inherited hemoglobinopathy, which results in production of abnormal hemoglobin S. HbSC disease is a variant of SCD, which shares a similar clinical complication profile to HbSS disease, but often thought to be a milder condition. In patients with SCD, Hb S in deoxygenated state undergoes polymerization, leading to hemolysis, vaso-occlusive events, and eventually end-organ damage. Among other complications in patients with SCD is increased risk of complications caused by parvovirus B19. We present a case of a 14-year-old female with HbSC disease who presented to the emergency room with complaint of abdominal pain and found to have splenic sequestration. Splenic sequestration progressed rapidly, Hemoglobin (hb) dropped to 4.6 g/dl and acute chest syndrome (ACS) developed. She was treated following the ACS protocol, received 4 units of Packed Red Blood Cells (PRBC) and subsequently underwent a single volume PRBC exchange transfusion. Considering her unusual presentation, with severe ARDS from alveolar hemorrhage requiring mechanical ventilation and multi-organ injury, several autoimmune and infectious conditions with a cytokine storm component including COVID-19 disease, were considered. Results of viral testing revealed parvovirus B19 IgM antibodies signifying an acute infection. She fully recovered with supportive care and was discharged home. Multisystem involvement simulating connective tissue disorders or malignancies with acute parvovirus B19 infection has been reported and is considered extremely rare. To our knowledge, there were no reports of pediatric patients with SC disease presenting with splenic sequestration and ACS in the setting of parvovirus B19 multisystem disease. Keywords: sickle cell disease; acute respiratory distress syndrome; acute chest syndrome; parvovirus B19.

Techniques for the Detection of Sickle Cell Disease: A Review.

Sickle cell disease (SCD) is a widespread disease caused by a mutation in the beta-globin gene that leads to the production of abnormal hemoglobin called hemoglobin S. The inheritance of the mutation could be homozygous or heterozygous combined with another hemoglobin mutation. SCD can be characterized by the presence of dense, sickled cells that causes hemolysis of blood cells, anemia, painful episodes, organ damage, and in some cases death. Early detection of SCD can help to reduce the mortality and manage the disease effectively. Therefore, different techniques have been developed to detect the sickle cell disease and the carrier states with high sensitivity and specificity. These techniques can be screening tests such as complete blood count, peripheral blood smears, and sickling test; confirmatory tests such as hemoglobin separation techniques; and genetic tests, which are more expensive and need to be done in centralized labs by highly skilled personnel. However, advanced portable point of care techniques have been developed to provide a low-cost, simple, and user-friendly device for detecting SCD, for instance coupling solubility tests with portable devices, using smartphone microscopic classifications, image processing techniques, rapid immunoassays, and sensor-based platforms. This review provides an overview of the current and emerging techniques for sickle cell disease detection and highlights the different potential methods that could be applied to help the early diagnosis of SCD.

Sickle cell vaso-occlusion: The dialectic between red cells and white cells.

The pathophysiology of sickle cell anemia, a hereditary hemoglobinopathy, has fascinated clinicians and scientists alike since its description over 100 years ago. A single gene mutation in the HBB gene results in the production of abnormal hemoglobin (Hb) S, whose polymerization when deoxygenated alters the physiochemical properties of red blood cells, in turn triggering pan-cellular activation and pathological mechanisms that include hemolysis, vaso-occlusion, and ischemia-reperfusion to result in the varied and severe complications of the disease. Now widely regarded as an inflammatory disease, in recent years attention has included the role of leukocytes in vaso-occlusive processes in view of the part that these cells play in innate immune processes, their inherent ability to adhere to the endothelium when activated, and their sheer physical and potentially obstructive size. Here, we consider the role of sickle red blood cell populations in elucidating the importance of adhesion vis-a-vis polymerization in vaso-occlusion, review the direct adhesion of sickle red cells to the endothelium in vaso-occlusive processes, and discuss how red cell- and leukocyte-centered mechanisms are not mutually exclusive. Given the initial clinical success of crizanlizumab, a specific anti-P selectin therapy, we suggest that it is appropriate to take a holistic approach to understanding and exploring the complexity of vaso-occlusive mechanisms and the adhesive roles of the varied cell types, including endothelial cells, platelets, leukocytes, and red blood cells.

Persistance of Inflammatory Phenotype of Neutrophils in Sickle Cell Disease Children Despite Chronic Exchange Transfusion Program: A Cause of the Progression of Cerebral Vasculopathy?

Sickle cell disease (SCD) is a severe hemoglobinopathy due to the production of abnormal hemoglobin S (HbS). Although red blood cell (RBC) dysfunction is the major contributor to disease, several studies highlighted the important role of polymorphonuclear neutrophils (PMNs), both during acute and chronic complications. One of the most severe complication of SCD is ischemic stroke due to large cerebral artery occlusion. In 1998, the Stroke Prevention (STOP) trial demonstrated that monthly blood transfusions could reduce the risk of stroke by 90% in SCD children with cerebral vasculopathy (CV). However, there is a wide heterogeneity in the course of CV in patients receiving chronic transfusions, since only about half of them improved their CV under transfusion program, while 25% are only stabilized and 29% continue to get worse despite a percentage of HbS permanently below 30%. The aim of our study is to investigate the impact of transfusion programs on neutrophils activation and ageing, in order to identify if inflammation could contribute to the persistence of SCD complications despite red cell transfusion. We performed a prospective study including 58 homozygous SCD children and 10 healthy donors. Of these, 12 had no specific treatment, 11 were on Hydroxyurea (HU) treatment, 21 were on an exchange transfusion program, and 14 were on both an exchange transfusion program and HU treatment for an average of 4.9 years due to persistent CV. Monthly exchange transfusion are carried out either by erythrapheresis or by manual exchanges, consisting of the continuous bleeding of whole blood compensated by simultaneous transfusion of packed red blood cells. Neutrophils were isolated from fresh blood samples before exchange transfusion session and labelled with 8 markers specific of adhesion, activation and ageing. We quantified by flow cytometry the expression of 3 integrins (CD18, CD11a, CD11b), 3 ageing markers (CD182, CD184, CD62L) and 2 adhesion molecules (CD162 and CD66a). We also measured the plasmatic level of elastase, which reflects the NETose activity of PMNs As previously reported, we observed a high leukocytosis and an activated profile of PMNs in the 12 non-transfused SCD patients compared to healthy controls (Figure 1), characterized by an overexpression of the integrin CD18/CD11b (p=0,03) and CD18/CD11a (p=0,02), a higher level of circulating aged PMNs CD184 high/CD62Llow (p=0,04), a higher expression of CD162 (p=0,01) and CD66a (0,01) as well as a higher plasmatic level of elastase (p=0.01). Interestingly, in the PMNs of the 21 patients receiving monthly exchange transfusion, we found an identical expression pattern of integrins, selectins, ageing markers and elastase level compared to those of the PMNs from non-transfused patients. Furthermore, we also observed a persistence of high neutrophilic leukocytosis. This activation pattern was the same for patients on manual exchange or erythrapheresis, even with a tendency towards a more inflammatory profile in patients on erythrapheresis (Figure 1). In the PMNs from the 11 patients receiving HU compared to untreated SCD patients, we found an expected decrease in high leukocytosis and membrane integrin expression CD18/CD11b and CD18/CD11a. The addition of HU therapy in 14 patients in exchange transfusion program allows to alleviate neutrophilic leukocytosis and membrane integrin expression. Our study shows for the first time that replacing sickle RBCs with healthy RBCs is not sufficient to reverse the pathological phenotype of PMNs in SCD. A persistence of the PMNs activation pattern is observed both despite erythrapheresis, where plasma and white blood cells go back to the patient, and in manual exchanges, where the patient is bled from a large volume of whole blood. Given the major role of inflammation in endothelial damage and vasculopathy in SCD, our data could explain the incomplete efficacy of transfusion exchange programs to treat CV. This raises the question to systematically combine anti-inflammatory and anti-white blood cell adhesion treatments such as Hydroxyurea or P-Selectin inhibitors for these patients. Disclosures No relevant conflicts of interest to declare.

Incidence of avascular necrosis of the head of the femur among sickle cell patients in Albaha region, Kingdom of Saudi Arabia

Background: Sickle cell disease (SCD) is an autosomal recessive disorder characterized by the production of abnormal hemoglobin S and is associated with high morbidity and mortality. The current study was aimed to determine the incidence of avascular necrosis (AVN) of the head of the femur in SCD patients in Al-Baha region. Methodology: A retrospective, descriptive cross-sectional study was conducted in the King Fahad Hospital located in Al-Baha region in the Kindom of Saudi Arabia. The patient's data collected were the well organized using a computerized system established in 2017. Results: The study showed a significant relationship between female gender SCD and developing AVN, 25 (56.8%). Among the total subjects, 44 patients were females, while only 19 patients were male. Furthermore, the study also found a strong statistically significant relationship between the incidence of AVN and recurrence. A total of 44 (24.3%) patients developed recurrence after AVN development. In 12.1% of them, the recurrence was in the left hip, while 9.0% had it on the right hip, followed by 4% on both the hip and only 2% has developed it on the left shoulder. Among the total, 97.7% of the study group were treated from AVN by replacement while 2.3% continued on conservative treatment. Conclusion: The incidence of AVN of the head of the femur among 24% of the study patients was considered less than that observed in countries of high incidence including Nigeria with 47% but still this percentage needs attention from health system as the avascular necroses of femur head could affect all aspect of life of the patients and health system economy.

Prevalence of Sickle Cell Disease and Other Haemoglobin Variants in Calabar, Cross River State, Nigeria

Background: Sickle cell disease (SCD) is the commonest genetic disorder worldwide with a global prevalence of 20-25 million. About 12-15 million affected persons are in Sub-Sahara Africa with Nigeria bearing the highest burden of people living with sickle cell disease. SCD is a disease characterized as an autosomal, recessive, heterogeneous, and a monogenetic disorder caused by an A-to-T point mutation in the β-globin gene responsible for the production of abnormal hemoglobin S (HbS), which polymerizes in the deoxygenated state and results in the sickling of erythrocytes. Haemoglobin variants are mutant forms of haemoglobin in a population usually occurring as a result of genetic changes in specific genes, or globins that causes change on alterations in the amino acid. They could affect the structure, behavior, the production rate and the stability of the specific gene. Well-known haemoglobin variants such as sick-cell anaemia are responsible for diseases and are considered haemoglobinopathies. Other variants cause no detectable pathology and are thus considered as non-pathological variants.
 Aim: The study is aimed at evaluating the burden of sickle cell disease and other haemoglobin variants in Calabar, South-South Nigeria.
 Methods: This is a retrospective study done at the haematology laboratory of University of Calabar Teaching Hospital, Calabar. Cellulose acetate electrophoresis at alkaline pH was used for the evaluation of haemoglobinopathies. The data were entered into Microsoft Excel 2016 spreadsheet and analysed with the IBM SPSS Version 22. Data were summarized into percentage of different phenotypes.
 Results: Results of the total 3648 haemoglobin electrophoresis recorded, 1368 (37.50%) were male while the remaining 2280 (62.5%) females given a male to female ratio of 1:1.7. Five haemoglobin phenotypes were identified as HbAA, HbAS, HbAC, HbSC and HbSS. The overall average values of their prevalence were HbAA 64.78%, HbAS 32.62%, HbSS 2.14%, HbAC 0.33%, HbSC 0.14%. Thus, the prevalence of SCD (Prevalence of HbSS+HbSC) was 2.28%. The highest proportion of SCD was observed in 2011 with least in 2016 and 2017 respectively.
 Conclusion: The prevalence of SCD and other haemoglobin variants in Calabar is similar to that of the national prevalence rate. There is need for continuous enlightenment and premarital counselling on the pattern of inheritance of SCD most especially with the increased burden of sickle traits in the environment has reported in this study.

Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry.

In sickle cell disease (SCD), a single point mutation in the gene coding for beta-globin causes the production of abnormal hemoglobin S (HbS). When deoxygenated, HbS can polymerize, forming rigid rods of hemoglobin, resulting in the sickling of red blood cells (RBCs). These sickled RBCs have significantly reduced deformability, causing vaso-occlusion, which leads to numerous SCD-related clinical complications, including pain, stroke, and organ damage. RBC deformability is also reduced by RBC dehydration, resulting in dense red blood cells that are more likely to sickle. To date, there is not a single widely available, rapid, and reproducible laboratory assay capable of predicting the disease severity or directly monitoring the treatment effects for novel, non-fetal hemoglobin inducing therapies. In this study, we describe a protocol to measure RBC deformability as a function of pO2 that allows for the quantitation of sickling behavior in SCD patients. Oxygen gradient ektacytometry measures RBC deformability, expressed as the elongation index (EI), as a function of pO2. RBCs are exposed to a fixed shear stress of 30 Pa during one round of deoxygenation and reoxygenation. Six readout parameters are produced. Of these, the point of sickling (PoS), defined as the pO2 at which maximum EI (EImax) shows a 5% decrease, and minimum EI during deoxygenation (EImin) are the most informative, reflecting an individual patient's pO2 at which sickling starts and the minimal deformability of a patient's red blood cells, respectively. PoS is associated with an individual patient's hemoglobin affinity for oxygen, whereas EImin shows a strong correlation with fetal hemoglobin levels. We conclude that oxygen gradient ektacytometry is a promising technique to monitor the treatment of patients with SCD, as a biomarker for anti-sickling agents in clinical and preclinical trials, and an important tool to study sickling behavior of RBCs from individuals with SCD and sickle cell traits.

Clinico-epidemiological profile of thalassemia patients in a tertiary care center

Introduction: Thalassemias are inherited blood disorders characterized by abnormal hemoglobin production. There are two main types, alpha thalassemia, and beta-thalassemia. Beta Thalassemia Major (also called Cooley's Anemia) is a serious illness. Symptoms appear in the first two years of life and include paleness of the skin, poor appetite, irritability, and failure to grow. There is absent or decreased production of normal hemoglobin, resulting in microcytic anemia of varying degrees. The thalassemias have a distribution concomitant with areas where P. falciparum malaria is common. The alpha thalassemias are concentrated in Southeast Asia, Malaysia, and southern China. The beta thalassemias are seen primarily in the areas surrounding the Mediterranean Sea, Africa, and Southeast Asia. Proper treatment includes routine blood transfusions and other therapies which can lead to iron overload and contraction of infections such as HIV, HCV, and HBV shortening the life span of patients. On the other hand, inadequate transfusions may lead to severe anemia and debility. Material and Methods: This retrospective record-based cross-sectional study was conducted in S.N. Medical College, Agra. Results: In our tertiary center, we have 103 registered patients of thalassemia, in which 44 are females and 59 are males. Out of the 103 thalassemia cases, 95 (92.2%) belonged to beta-thalassemia major, 4(3.8%) of beta-thalassemia intermediate, and 1 (0.9%) of beta-thalassemia minor category. Fever was the most common presenting symptom. Pallor and hepatomegaly were the most common signs among cases. Conclusion: Hemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other hemoglobinopathies in different caste/ethnic groups of India is scarce.

Altered Collection Interfaces in Hematopoietic Progenitor Collection of Sickle Cell Patients

Abstract Sickle cell disease (SCD) results from a point mutation in the beta globin gene leading to abnormal hemoglobin production and, correspondingly, abnormal sickling of erythrocytes that result in chronic anemia and vaso-occlusive crises. Patients with sickle cell are commonly treated with lifelong transfusions or hydroxyurea to increase fetal hemoglobin to ameliorate sickling. Evolving therapies are aimed at correcting known mutations with gene therapy on autologous hematopoietic stem and progenitor cells (HSCs), indicating a growing need for optimal stem cell collections from SCD patients. Recent studies have shown the safety and efficacy of plerixafor to increase peripheral CD34+ cells, enhancing collection. Here we show that standard apheresis collection procedures from sickle cell patients are inefficient when compared to healthy donors. Eleven patients with SCD were recruited to receive plerixafor and followed by peripheral CD34+ cell monitoring and apheresis collection. Overall, efficiency ranged from 2% to 55% with no correlation to total peripheral CD34+ cell count. To better understand where the CD34+ cells sedimented in the apheresis instrument, we collected different layers of the interface ranging from 3% to 10% estimated Hct and found that deeper layers with higher hematocrit (7.5%-10%) are enriched for CD34+ cells when compared to historical donors with healthy red cells. All patients had undergone red cell exchange prior to collection, yet this intervention did not prevent the altered sedimentation of CD34+ cells. These findings indicate that CD34+ cells from SCD patients sediment at a deeper, higher Hct interface layer during apheresis and support the altered collection practices for the efficient collection of HSCs for cellular therapies.

PB2314 CHRONIC NEUTROPHILIC LEUKEMIA IN A SICKLE CELL PATIENT WHO SURVIVED CBF‐ACUTE MYELOID LEUKEMIA

Background:Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm, for which current WHO diagnostic criteria include leukocytosis of ≥25 × 109 /L of which ≥80% are neutrophils, with <10% circulating neutrophil precursors with blasts rarely observed. In addition, there is no dysplasia, nor clinical or molecular criteria for other myeloproliferative neoplasms. The true incidence of CNL is unknown, but only 200 cases have been reported.Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production(HbS) which leads to hemolytic anemia and intermittent occlusion of small blood vessels.Aims:Case report of a 55 years old patient with double heterozygous sickle cell/β + thal disease, first diagnosed at age of 45, who now suffers from CNL, ten years post treatment for acute myeloid leukemia (AML).Methods:A 55 years old male patient was referred to our clinic in 2012 with the diagnosis of double heterozygous sickle cell/β + thal disease. He was initated on red cell exchange transfusions due to sickle cell hepatopathy. Ten years earlier he had received intensive chemotherapy for AML with myelomonocytic differentiation, CBFB/MYH11(+). He attained a complete morphological and cytogenetic remission after 1st induction. He remained in CR until 2015 when he presented with worsening anemia that could not be attributed to his hemoglobinopathy(Hb = 8 g/dl). A complete work up including bone marrow aspiration, biopsy, molecular testing for CBFB/MYH11 and cytogenetics were normal. In 2018, he presented with a severe sickle cell crisis with multi‐organ failure during an infection and he started hydroxycarvamide at a dose of 500 mg. During the next months a progressive increase of WBC counts with elevated neutrophils was noticed and was attributed to dental abscess. Leukocytosis insisted despite appropriate treatment so he was admitted to the clinic. A complete work up, including imaging, virology, blood and urine cultures revealed no sign of infection or malignancy. Despite hydroxycarbamide treatment leukocytosis persisted (WBC: 90 × 109/L, ≥95% neutrophils, Hb: 8 g/dl, PLT:180000), with no circulating neutrophil precursors or myeloblasts and no evidence of dysplasia.Bone marrow biopsy was repeated. This time an hypercellular marrow with increased neutrophils, normal maturation and blasts <5% raised the question of a myeloproliferative neoplasm. The patient did not fulfill WHO criteria for Ph + CML, PMF, PV or ET. Analysis of a myeloid panel by Next generation sequencing(NGS) revealed the presence of the following mutations: CSF3R T618I, VAF:38% and SETBP1 G870Ser, VAF:54%.Results:A diagnosis of Chronic Neutrophilic Leukenmia was made according to the WHO classification. Hydroxycarbamide at a dose of 2gr was started,since patient was not eligible for bone barrow transplantation. Five months later,patient remains in good condition and has no evidence of disease progression.Further investigation will involve the detection of driver mutations in the bone marrow sample from the primary AML diagnosis using NGS.Summary/Conclusion:Although the clinical course of CNL is variable, the overall prognosis is generally reserved with a substantial portion of patients eventually progressing to blast crisis,The median overall survival is 24 months. Effective management has been hampered by the rarity of the disease, the lack of prospective trials, and the limited therapeutic options.The most common therapeutic approaches are Hydroxyurea, Interferon and Ruxolitinib. Our patient shows an initial response in Hydroxyurea therapy.

Mechanisms of NRF2 activation to mediate fetal hemoglobin induction and protection against oxidative stress in sickle cell disease.

Sickle cell disease (SCD) is a group of inherited blood disorders caused by mutations in the human β-globin gene, leading to the synthesis of abnormal hemoglobin S, chronic hemolysis, and oxidative stress. Inhibition of hemoglobin S polymerization by fetal hemoglobin holds the greatest promise for treating SCD. The transcription factor NRF2, is the master regulator of the cellular oxidative stress response and activator of fetal hemoglobin expression. In animal models, various small chemical molecules activate NRF2 and ameliorate the pathophysiology of SCD. This review discusses the mechanisms of NRF2 regulation and therapeutic strategies of NRF2 activation to design the treatment options for individuals with SCD.

Early Predictors of Renal Dysfunction in Pediatric Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy characterized by abnormal hemoglobin production which leads to hemolytic anemia and intermittent occlusion of small blood vessels, which further leads to tissue ischemia, chronic organ damage, and organ dysfunction including urinary system. To measure the serum levels of cystatin-C and beta 2 microglobulin in pediatric patients with SCDand to investigate their significance as early biomarkers of glomerular and/or renal tubular dysfunction. This study was conducted among 70 children with SCD and 40 age and sex-matched children as a control group. All subjects underwent a full medical history, through physical examination, laboratory investigations including blood urea, serum creatinine, serum ferritin, estimated glomerular filtration rate (eGFR) using the Schwartz formula, creatinine clearance, urinary albumin/creatinine ratio, serum cystatin-C, and β-2 microglobulin levels. Pediatric patients with SCD had significantly higher serum cystatin-C and β-2 microglobulin levels compared to controls. In addition, serum cystatin-C and β-2 microglobulin levels were positively correlated with blood urea, serum creatinine, serum ferritin, urinary albumin/creatinine ratio, duration of iron chelating agents and frequency of blood transfusion/year. Serum cystatin-C and β-2 microglobulin levels were negatively correlated with hemoglobin. Our data concluded that serum cystatin-C and β-2 microglobulin had highersensitivity and specificity (91%, 90% and 85.7%, 100%, respectively) than serum creatinine (79% and85%, respectively). Serum Cystatin-C and β-2 microglobulin are early specific and sensitive biomarkers for evaluating glomerular and tubular dysfunction in children with SCD.

The Importance of Demodex Mites (Acari: Demodicidae) in Patients With Sickle Cell Anemia.

Although demodicosis caused by Demodex folliculorum and Demodex brevis is widely seen throughout the world, the pathogenic mechanisms are not fully known. To the best of our knowledge, the effect of Demodex mites in patients with sickle cell anemia (SCA) is not known. SCA is a genetic disease characterized by abnormal hemoglobin production and suppression of the immune system. The aim of this study was to determine the prevalence and Demodex density in SCA patients and to compare with healthy subjects. The study included 70 patients diagnosed with SCA and control group of 50 healthy individuals. Samples were taken from cheeks, forehead, nose, and chin and were examined microscopically. Infestation of ≥5 mites/cm2 was accepted as positive in the diagnosis. Demodex mite positivity was determined in 20 (28.6%) patients and none in subjects of the control group. In the SCA group, the mean number of mites was 26.10/cm2. A statistically significant correlation was found between Demodex mite positivity and the number of SCA symptom attacks experienced by the patients within the last 1 yr (P ≤ 0.001). No significant relationship was determined between Demodex mite positivity and age or gender (P = 0.56 and P = 0.11, respectively). Demodex mites are seen more often in SCA patients who suffer from a compromised immune system, and the presence of Demodex mites could be a risk factor in the appearance of SCA symptom attacks.

An Assessment of Knowledge towards Complications of Sickle Cell Disease among General Population in Jeddah City

Background: Sickle cell disease (SCD) is an autosomal recessive disorder characterized by production of abnormal hemoglobin S, and it is associated with high morbidity and mortality. The highest prevalence of SCD in Saudi Arabia is in the Eastern province. Objectives: To assess perceptions and the level of knowledge about SCD and to study factors that may affect them among general population in Jeddah city, Saudi Arabia. Methods: A self-administered questionnaire was distributed among general population residing in Jeddah city, Saudi Arabia. The questionnaire consisted of two sections: (1) socio-demographic information and previous experience with SCD and (2) knowledge about SCD and its complications, which was measured by 20 closed-ended questions. Results: A total of 424 subjectscompleted the questionnaires and participated in the study. More than half (51.4%) of the participants showed good level of knowledge about SCD and its complications. Sex, education level, and previous experience with SCD child had significant association with the level of knowledge (p<0.05). The majority of participants with good level of knowledge were females (86.2%) and at the level of university education (84.4%). Furthermore, all subjects (100%) who had previous experience with SCD child showed good level of knowledge. Conclusion: A moderate level of awareness regarding SCD and its complications was found in our study sample. Educational programs should target the male population and emphasize the nature of inheritance of the common blood diseases and their complications.

Sickle cell disease: Where are we now?

SICKLE CELL DISEASE (SCD) is a group of inherited red blood cell (RBC) disorders that cause the production of abnormal hemoglobin (Hb), the oxygen-carrying component of the RBC. SCD is a chronic disease that can cause many systemic complications, such as organ dysfunction and infection due to inadeq

Sickle Cell Trait and Renal Function in Hispanics in the United States: The Northern Manhattan Study.

Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and CKD was defined as eGFR < 60 mL/min/1.73 m2. Within our sample, there were 16 individuals with SCT (SCT carriers). We found that SCT carriers had a mean eGFR that was 12.12 mL/min/1.73m2 lower than non-carriers (P=.002). Additionally, SCT carriers had 2.72 times higher odds of CKD compared with non-carriers (P=.09). Taken together, these novel results show that Hispanics with SCT, as found among African Americans with SCT, may also be at increased risk for kidney disease.

Dense red blood cell and oxygen desaturation in sickle-cell disease.

Production of abnormal hemoglobin (HbS) in sickle-cell disease (SCD) results in its polymerization in deoxygenated conditions and in sickled-RBC formation. Dense RBCs (DRBCs), defined as density >1.11 and characterized by increased rigidity are absent in normal AA subjects, but present at percentages that vary of a patient to another remaining stable throughout adulthood for each patient. Polymerized HbS has reduced affinity for oxygen, demonstrated by the rightward shift of the oxygen-dissociation curve, leading to disturbances in oxygen transport. Ninety-two SCD patients' total RBCs were separated into LightDRBC (LRBC) (d < 1.11 g/mL) and DRBC fractions. Venous blood partial oxygen pressure and RBC-fraction-deoxygenation and -reoxygenation Hb-oxygen-equilibrium curves were determined. All patients took a 6-minute walking test (6MWT); 10 had results before and after >6 months on hydroxyurea. 6MWT time with SpO2 < 88% (TSpO2 < 88) assessed the physiological impact of exertion. Elevated mean corpuscular hemoglobin (Hb) concentrations, decreased %HbF, and 2,3-bisphosphoglycerates in DRBCs modulated Hb-oxygen affinity. Deoxygenation and reoxygenation Hb-oxygen equilibrium curves differed between normal Hb AA and SS RBCs and between LRBCs and DRBCs, with rightward shifts confirming HbS-polymerization's role in affinity loss. In bivariate analyses, 50% Hb saturation correlated positively with %DRBCs (P < 0.0001, r(2) = 0.34) and negatively with %HbF (P < 0.0001, r(2) = 0.25). The higher the %DRBCs, the longer the TSpO2 88 (P = 0.04). Hydroxyurea was associated with significantly shorter TSpO2 < 88 (P = 0.01). We report that the %DRBCs directly affects SCD patients' SpO2 during exertion; hydroxyurea improves oxygen affinity and lowers the %DRBCs. Am. J. Hematol. 91:1008-1013, 2016. © 2016 Wiley Periodicals, Inc.

Splenectomy in Patients with Sickle Cell Disease in Tabuk.

BACKGROUND:Sickle cell disease is a common genetic disease in Saudi Arabia; it is an autosomal recessive disorder characterized by production of abnormal hemoglobin S and is associated with high morbidity and mortality. Acute splenic sequestration is a life-threatening complication for this disease. Prophylactic splenectomy is the only effective strategy for preventing future life-threatening episodes.AIM:The aim of this study was to study hospital records for all children aged 2 to 12 year old with Sickle cell disease who underwent splenectomy in Tabuk in Saudi Arabia.METHODS:Records of 24 children (13 males, 11 females) who underwent splenectomy in surgery department of King Salman North West Armed Hospital, Tabuk, Saudi Arabia between 2008 and 2015 were reviewed retrospectively and analyzed for age, sex, indications for splenectomy, surgical technique, preoperative and postoperative length of stay, operative and postoperative complications, acute chest syndrome, painful crises, blood transfusion and fever (preoperative and postoperative).RESULTS:We stressed on the information about the details of operation, the frequency of blood transfusion, fever, acute chest syndrome and painful crisis before and after operation.CONCLUSION:Here we found that blood transfusion frequency decreased after splenectomy.

Unraveling the origin of splice switching activity of hemoglobin β-globin gene modulators via QSAR modeling

β-Thalassemia is a blood disease caused by a mutation in the second intron of the β-globin gene of hemoglobin that leads to abnormal hemoglobin production. Low molecular weight compounds have been proposed to modulate defective splicing by binding unwanted splicing sites, thereby restoring correct splicing. This study investigates the origin of this splice switching activity in a set of 39 active and 61,000 inactive compounds. The K-means algorithm was applied to the inactive compound points with 39 clusters, in which a point from each cluster was selected to create a balanced data set of 39 active and inactive compounds. To avoid random bias, predictive models (i.e., decision tree (DT), random forest (RF), artificial neural network (ANN), partial least squares discriminant analysis (PLS-DA) and support vector machine (SVM)) were constructed 50 times. The performances of the predictive models were statistically assessed in terms of accuracy, sensitivity, specificity and Matthews correlation coefficient (MCC). RF provided an accuracy of 89.50±13.45, sensitivity of 94.97±13.49, specificity of 84.29±22.27, and MCC of 0.80±0.25 for 10-fold CV, and it provided and accuracy of 88.00±8.55, sensitivity of 87.89±13.93, specificity of 87.51±13.75, and MCC of 0.75±0.18 for external testing. Taking advantage of the built-in feature selector of RF, a thorough analysis of feature importance was conducted. Newly identified fingerprint substructures, namely, three carbon-hetero bonds (i.e., secondary amide, tertiary amide, carboxyl derivative, carboxylic acid derivative and nitrile), carbon-carbon bonds (i.e., primary carbon, secondary carbon and alkene), aromatics (hetero N nonbasic) and carbon-hetero bond (alkyl aryl ether), may provide a better understanding of the structural variations governing the splice switching activity of the hemoglobin β-globin gene.