Sickle Thalassemia Research Articles

Molecular genotyping versus serological diagnosis for RH blood group typing in sickle cell patients

ABSTRACT Objectives High rate of alloimmunization in sickle cell disease (SCD) patients poses a significant challenge in finding compatible blood unit. Accurate determination of the blood group genotype of them can help reduce the alloimmunization risk. Tetra ARMS PCR is a novel method that has been utilized recently to investigate SNPs in diseases in a fast and reliable way. Methods Our study included 104 SCD and sickle thalassemia (Sβ) patients referred to Baghaei-2-Hospital of Ahvaz in 2019 using a nonrandom sampling method. Blood samples were collected for serological and molecular tests. Rh genotyping was performed using Tetra ARMS PCR and compared with the serological results. Results Based on the Tetra ARMS PCR method, out of 104 patients, 7 (6.7%) were d/d, 40 (38.5%) were D/d, 57 (54.8%) were D/D, 25 (24%) were C/C, 59 (56.7%) were C/c, 20 (19.3%) were c/c, 4 (3.8%) were E/E, 25 (24%) were E/e, and patients 75 (72.2%) were e/e. There were discrepancies in the serological and molecular results for 11 patients. Conclusion Use of Tetra ARMS PCR in combination with serological methods for determining the Rh blood group system in donors and transfusion-dependent patients represents a remarkable transformation in the field of immunohematology.

Osteonecrosis of the femoral and Humoral heads in sickle disease patients: Risk factor, Comorbiditis

ObjectivesAVN is the most common in Sickle Cell Disease patients, as SCD is common in the Jazan region of Saudi Arabia. The risk factors, and comorbidity regarding AVN of hip and shoulder joints in SCD patients were investigated in this study. MethodsThis retrospective cohort study was conducted at the two biggest hospitals in the Jazan region. A valid data collection sheet was used to collect information of SCD patients admitted to the wards or during follow-up. Staging for HAVN and SAVN was based on FICAT classification guidelines. Descriptive statistics and multivariate logistic regression were utilized. Resultstotal number of participants is 257, and 99 (38.5%) were under 14 years of age. About half of the participants are (134) females. Regarding participants' hemoglobin type, 78.6% had SCD, while 21.4% had sickle thalassemia. The occurrence of HAVN and SAVN is 14.8% and 5.4%, respectively. Of the 38 HAVN participants, 26.3% had comorbidities, and 5.3% had hypertension. The SAVN participants didn't report diabetes or hypertension. The vascular occlusive crisis is the most significant complication associated with SCD. Multivariate logistic regression determined some risk factors for SAVN and HAVN. ConclusionAVN is a frequent consequence of SCD, where the incidence rises with age. The vascular necrosis is the most significant complications. Continuing research on the prevention and non-surgical treatments of AVN caused by SCD must remain a top focus.

Assessment of Cardio-Pulmonary and Renal Dysfunction As Well As Overall Outcomes in Sickle Cell Patients: A Community Hospital-Based Experience

Background: Improvements in medical care for Sickle Cell Disease (SCD) patients in the USA has led to increased survival rates, however, management of comorbidities associated with end organ damage remains challenging. ASH 2019 guidelines do not recommend obtaining screening echocardiogram in asymptomatic SCD patients but suggest management of confirmed Pulmonary Arterial Hypertension (PAH) with specific therapies. For those with Chronic Kidney Disease (CKD) or End Stage Renal Disease (ESRD) requiring dialysis, it is recommended to treat with combination of hydroxyurea and erythropoiesis-stimulating agents as well as consider early referral to transplant nephrology. Our study was aimed to assess the correlation between various characteristics, underlying comorbidities with cardio-pulmonary and renal dysfunction as well as overall outcomes in SCD patients treated at the Henry Ford Hospital sickle cell clinic. Methods: A retrospective chart review of 105 patients between June 2013-June 2022 was performed. Baseline characteristics including gender, ethnicity, BMI, presence or absence of various comorbidities such as acute chest syndrome, Congestive Heart Failure (CHF), PAH, Deep Vein Thrombosis (DVT)/Pulmonary Embolism (PE), CKD, ESRD requiring dialysis, use of medications such as folic acid, hydroxyurea and newer therapies including voxelotor, crizanlizumab and L-glutamine were obtained. Frequency of ER visits, hospitalizations and blood transfusion requirements were noted. Patients were divided in 2 groups- SS Disease including Sickle/Thalassemia (ST) and SC disease. Continuous variables were compared via ANOVA/Kruskal Wallace Test and categorical variables were compared via Chi Squared Test/Fisher's Exact Test. Results: In our study, 49.5% were females, 95% were African-American. SS/ST disease type was seen in majority (62.8%) followed by SC disease and 2 patients had sickle cell trait. SS/ST patients were noted to have elevated HbS, reticulocyte count and LDH levels as expected compared to SC disease, whereas those with SC disease were noted to have higher BMI levels likely due less complications. SS/ST patients were more significantly noted to have diagnosis of CHF (p=0.020) as well as CKD (p=0.029). Interestingly, ESRD requiring dialysis was only seen in SS/ST patients. 69.6% of all patients underwent an echocardiogram evaluation and 28.7% of those had a diagnosis of PAH. In our study, 23.8% with PAH were started on newer therapies. 88.5% of all patients were compliant with folic acid treatment and 34.2% were started on hydroxyurea with significantly higher treatment in those with CHF and elevated HbS levels. Overall, 15.9% patients were started on newer therapies and their use was noted to be significantly higher in patients with CKD and ESRD (p=0.011 and p=0.029 respectively). Hospitalizations were less frequent in patients with SC disease compared to SS/ST although not statistically significant (p=0.80) and frequency of ER visits was not significantly different between both groups. Also, patients were less frequently hospitalized if they received chronic simple transfusions on outpatient basis. Conclusion: SS disease patients at our institution had increased likelihood of developing CHF as well as CKD. Of note, those with CKD or ESRD were also more likely to be placed on newer therapies. Based on these findings, we have developed a multidisciplinary management care plan alongside nephrology service. In our study, about a third of total patients did not have an echocardiogram evaluation, however, 28% of those who had an echocardiogram were noted to have PAH. Therefore, we think that use of screening echocardiogram in all SCD patients could help with early diagnosis of PAH and prompt referral to pulmonary medicine team to prevent potential complications. Use of hydroxyurea was noted to be significantly higher in those with CHF and newer therapies were more frequently used in patients with CKD and ESRD in our patients. These results encourage better utilization of such therapies in SCD patients with other comorbidities as well as those who have frequent hospitalizations to improve outcomes in the future. SCD related end organ damage is increasing in incidence with improvement in survival rates and poses a challenge which demands a multidisciplinary system-based care approach. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A study of spectrum of sickle cell anemia and thalassemia in a teaching institute of South India.

Sickle cell syndrome is a group of inherited hematological disorders with varying degrees of anemia, jaundice, fatiguability along with hepatomegaly and splenomegaly. The clinical presentations can be may vary and therefore require thorough investigations. We tried to evaluate the spectrum of sickle cell anemia and thalassemia in pediatric patients of our hospital. In this cross-sectional study, A total of n = 200 consecutive cases were detected during the period of study. A thorough history and detailed clinical examination were done. Hb electrophoresis was done in the present study using HYDRASYS ® Electrophoresis Systems from Sebia. The overall prevalence of SCD in our study was 6.83% the existence of this is found to be greater in the males as compared to females which is in agreement with prevalence across India with more male than female. Thalassemia was prevalent at the rate of 3.96%, sickle cell anemia had a prevalence of 1.98% sickle thalassemia was 0.89%. N = 20 pairs of Parents recognized genetic counseling i.e., with a single child or who wanted further children readily underwent HPLC analysis. The existence of SCD in our study group is lesser as compared to the South India average. Preventive programs consisting of public education, population screening, genetic counseling, and prenatal diagnosis have been very effective in reducing both rates of β-Thalassemia major. Sickle cell anemia is of prime importance because of its high prevalence, morbimortality and the absence of curative treatments.

Impact of Alloimmunization in Patients with Sickle Cell Disease

INTRODUCTIONBlood transfusion is an essential therapeutic and prophylactic component in the management of sickle cell disease (SCD) and associated complications. Prolonged transfusion therapy can lead to the development of antibodies to the donor's RBC antigens (alloimmunization), causing complications such as delayed hemolytic transfusion reactions, hyperhemolysis, worsening vaso-occlusive episodes, and end-organ damage. There have been only a few case series highlighting the impact of RBC alloimmunization on SCD morbidity and mortality, proposing a pathway involving RBC alloimmunization and decreased survival associated with hemolytic reactions or difficulty obtaining compatible blood when needed. However, apart from the consequences of iron overload, there is no long-term data for alloimmunization highlighting the clinical consequences, multiorgan damage, or associated morbidity in sickle cell patients.AIMThe primary aim is to investigate the incidence of alloimmunization in SCD patients in an academic health system. The secondary aim is to elucidate the differences in demographics, frequency of vaso-occlusive crisis, end-organ damage, and inflammatory markers between alloimmunized and non-alloimmunized SCD patients.METHODSWe conducted a retrospective multicentric descriptive study, including all sickle cell patients treated in an academic health system from January 1st, 2009, to December 31st, 2020, in Maryland, Virginia, and Washington, DC. An exemption from the Institutional Review Board for obtaining individual subjects' consent was procured. Patients included in the study were older than 18 years and diagnosed with sickle cell disease. Patients who did not have sickle cell disease were excluded from the study. Statistical analysis was reported using means for descriptive data, t-test for continuous variables, and chi-square for categorical variables.RESULTSA total of 94 patients with sickle cell disease were included in the study. Of these, 24 (25.5%) patients were found to have alloimmunization, whereas 70 (74.4%) patients did not. Of the alloimmunized patients, the average age, BMI and BSA were 30.15 years (p=0.037), 23.15 kg/m2 (p=0.040), and 1.65 m2 (p=0.003) compared to 37.07 years, 26.17 kg/m2 and, 1.84 m2 respectively among the non-alloimmunized group. 83% of the alloimmunized patients had sickle cell anemia (Hb SS), and 17% had a sickle thalassemia phenotype (p=0.005). A lower baseline hemoglobin (Hb) value of 8.01 g/dL was seen among alloimmunized patients compared to a higher Hb value of 9.63 g/dL (p=0.001) among the non-alloimmunized. Alloimmunized patients had an average of 5.55 alloantibodies. The average number of vaso-occlusive crises per year and related hospitalizations was statistically significantly higher in the alloimmunized group with 4.82 and 3.78, respectively, compared to 2.34 (p=0.035) 1.01 (p=0.0005) in the non-alloimmunized group. Similarly, the incidence of other sickle cell-related complications were higher among the alloimmunized patients, such as priapism (29% vs. 9%; p=0.0139), pulmonary hypertension (38% vs. 9%; p=0.0038) with no statistical difference in the iron overload (25% vs. 11%; p=0.150) or ferritin levels (. 83% of alloimmunized patients had a history of narcotic use vs. 34% among the non-alloimmunized (p=0.0001). Higher use of disease-modifying therapies including hydroxyurea (71% vs. 31%; p=0.0009) and voxelotor (13%vs0; p=0.0029), were also seen among alloimmunized patients. While no statistically significant difference was seen in the mean number of lifetime transfusions, there was a difference in the mean number of lifetime exchanges (3.67 vs. 0.0; p=0.0208).CONCLUSIONThe prevalence of alloimmunization in sickle cell patients in our study population (25.5%) was higher than in the literature (7- 59%) and the general population (2%). An increase in alloimmunization was associated with an increased number of exchanges but not with simple transfusions. Independent from the iron overload, alloimmunization was associated with increasing end-organ damage and sickle cell complications such as priapism, pulmonary hypertension. Strategies to decrease alloimmunization are needed to prevent these complications. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Study of transcranial Doppler ultrasound and endothelin-1 in children with sickle cell anemia: a single-center study

To assess the impact of our transcranial Doppler (TCD) screening program on the incidence of a first stroke in children with sickle cell anemia and to study the role of elevated serum endothelin-1 (an inflammatory mediator) in these children. Background: stroke is a major complication of sickle cell disease (SCD), even in very young children. About 11% of children with homozygous sickle cell anemia (SS) develop stroke by the end of the second decade of life. The underlying etiology in most cases is an ischemic stroke caused by large-vessel stenosis or occlusion. Transcranial Doppler (TCD) recommended as a routine screening test to identify children at high risk of developing a stroke, measures flow velocities within large intracranial arteries. TCD should be routinely performed in children between 2 and 16 years as this age group is at the highest risk of sickle cerebral vasculopathy. We carried out a prospective case-control study which included 2 groups: a patient group consisted of 30 children with sickle cell anemia and sickle thalassemia and a group of 30 healthy children of matched age and sex. Each group included 11 males (36.5%) and 19 females (63.5%); the age range was 2 to 17 years. Both groups underwent a thorough clinical examination and laboratory tests (CBC, liver and renal function, serum ferritin and endothelin-1). Additionally, TCD was performed in all children included in the patient group. According to the results of TCD, time-averaged mean of the maximum velocity (TAMMX) was < 170 cm/s (normal), 170–200 cm/s (conditional), ≥ 200 cm/s (high risk) in 20 (66.7%), 4 (13.3%) 6 (20%) patients, respectively. The level of endothelin-1 was significantly higher in the patients (57.1 ± 91.3) than in the controls (21.9 ± 14.8). Hemoglobin concentration was significantly lower in the patient group than in the control group, but the levels of reticulocytes, WBCs and serum ferritin were significantly higher in the patients than in the healthy controls. Serum Endotheline-1 level was higher in patients with sickle cell anemia than control group.

English

BACKGROUND Sickle delta beta thalassemia is a rare genetic disorder, with varied symptoms, signs, requiring careful monitoring for potential complications. It is due to sickle mutation and thalassemia mutation occurring together, with sparse data available worldwide. The purpose of this study was to assess the clinical and laboratory profile of possible sickle delta beta thalassemia. METHODS The study design is retrospective analysis of clinical information of those selected patients done in our multi-specialty tertiary care referral hospital situated in Telangana state in south India. The case material was collected from December 2017 to December 2019 (2 years duration). All haemoglobin electrophoresis reports were collected with no prior blood transfusions in preceding 4 months. The information collected was analysed and presented. RESULTS Total 9 patients were diagnosed as possible sickle delta beta thalassemia, with male to female ratio of 5 : 4 and age ranging from 12 years to 45 years of age. The commonest symptoms were joint pain and jaundice in 5 patients and sign was splenomegaly in 2 patients. Ultrasonogram of abdomen showed that 3 patients had gall stones, 1 patient had gall bladder sludge, 1 patient had autosplenectomy and 3 patients had splenomegaly. Mild to moderate anaemia was seen with reticulocytosis, sickling test positive in all patients, with haemoglobin in the range of 5.5 g/dl to 12.7 g/dl. 3 patients had iron over load, 2 patients had hepatopathy, 5 patients had unconjugated hyperbilirubinemia, Acute chest syndrome, hepatic necrosis, and nephropathy was seen in 1 patient each. Haemoglobin electrophoresis showed Hb S was from 46.1 % to 76.4, Hb A from 5.3 % to 34.7 %, Hb F from 4.8 % to 22.7 %, Hb A2 from 1.5 % to 3.3 %. 2 patients were treated with hydroxyurea. 2 patients had mutation analysis elsewhere that was reported as compound heterozygous for β-globulin gene for Hb S (GAG-GTG) and IVS 1 - 5 (G-C). CONCLUSIONS Sickle delta beta thalassemia presents as mild to moderate anaemia haemolysis, splenomegaly with vaso-occlusive crises. Hydroxyurea may help in the treatment. Genetic analysis helps in diagnosis and future therapies. KEYWORDS Haemoglobin S, Haemoglobin A2, Haemoglobin A, Haemoglobin F

Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study

Sickle Cell Disorders and Severe COVID-19 Outcomes: A Cohort Study

The Rh blood group system and its role in alloimmunization rate among sickle cell disease and sickle thalassemia patients in Iran.

IntroductionThe alloimmunization following blood transfusion can be life‐threatening. The Rh alloantibodies are one of the most common causes contributing to alloimmunization. This study aimed to evaluate the rate and causes of alloimmunization and to determine the Rh phenotypes and genotypes among sickle cell disease (SCD) and sickle thalassemia (Sβ).Materials and MethodsOur study included 104 SCD and Sβ patients referring to Baghaei 2 Hospital of Ahvaz in 2019 using a non‐random simple sampling method. The blood samples were collected for Rh phenotypes, alloantibody screening and identification, and molecular tests. The SSP‐PCR and RFLP methods with the Pst 1 enzyme were used.ResultsThe alloimmunization rate was 9.6% and 13.2% based on immunohematological tests and medical records, respectively. The main alloantibodies (90%) were anti‐Rh, and 40% of the patients had multiple alloantibodies. A significant correlation was found between gender and alloimmunization. The phenotypes of DCce (37.5%), DCcEe (24%), Dce (20.2%), and dce (5.8%) and genotypes of R1r (25%), R1R2 (20.2%), R1R1 (18.3%), and R1R0 (10.6%) were the most prevalent. The R1R2 was a frequent genotype in Sβ.ConclusionR0r′ and R1R0 genotypes were limited to our population in Iran. Due to the differences in RH genotypes between our population and others, the blood transfusion from other ethnicities increased our total alloimmunization rate.

Renal Papillary Necrosis as the First Presenting Clinical Feature in a Sickle Beta and Thalassemic Child

In sickle cell disease (SCD), the clinical manifestations are due to episodes of vascular occlusion and haemolysis. Most of the children experience vaso-occlusive pain episodes by the age of six years. Renal injury in sickle cell disease referred to as sickle cell nephropathy is a frequent yet under-recognised complication. Renal papillary necrosis (RPN) as the first presentation in SCD is rare. We are reporting a 12 year old child with no prior vaso-occlusive episodes, presenting with renal papillary necrosis due to Sickle Beta and Thalassemia.

Severe Malnutrition and Anemia Are Associated with Severe COVID in Infants.

ABSTRACTBackgroundCOVID-19 is uncommon and less severe in children than adults. It is thought that infants may be at higher risk for severe disease than older children. There is a paucity of literature on infants with COVID, particularly those with severe disease.ObjectiveWe describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of infants with confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, IndiaMethodologyInfants who tested positive for SARS-CoV-2 and were admitted between 1 April 2020 and 7 August 2020 were included in the study.ResultsA total of 13 infants were admitted during the study period. The median age was 8 months (IQR 6) and nine were male. Common presenting features were fever (n = 8, 62%), poor feeding, irritability, and runny nose (n = 3, 23%). Comorbidities noted were severe acute malnutrition (SAM) in three cases (23%) and nutritional megaloblastic anemia, iron deficiency anemia, sickle thalassemia and renal calculi in one case (8%) each. There was a history of low birth weight in two cases (15%). Pallor was noted in three cases (23%), SAM in three cases (23%) and tachypnea and respiratory distress in four cases (30%). Severe anemia, thrombocytopenia, elevated ferritin, abnormal procalcitonin, abnormal C Reactive Protein and deranged D-dimer was noted in three cases (23%) each. Neutrophil–lymphocyte ratio was normal in all cases. Three infants (43%) had evidence of pneumonia on the chest radiograph, of which one had adult respiratory distress syndrome (ARDS) like pattern, one infant had cardiomegaly and perihilar infiltrates. Hydroxychloroquine and azithromycin were given to five patients (38%), Intravenous Immunoglobulin and methylprednisolone were administered to one patient (8%). One infant died of ARDS with multi-organ dysfunction with refractory shock and hemophagocytic lymphohistiocytosis. ConclusionSAM and anemia may be associated with severe COVID in infants.

15th Annual Sickle Cell and Thalassaemia, 1st EHA European Sickle Cell Conference, and 60th Anniversary of BSH Abstract Book

15th Annual Sickle Cell and Thalassaemia, 1st EHA European Sickle Cell Conference, and 60th Anniversary of BSH Abstract Book

Evaluation of Protein S and Protein C Levels in B-Thalassemic Patients and Its Association with Blood Transfusion

Background: Thalassemia is a chronic hemolytic anemia due to a partial or complete deficiency in the synthesis of α-globin chains or β-globin chains that compose of the major adult hemoglobin (α 2β 2). Protein C is a vitamin K-dependent serine protease and naturally occurring anticoagulant that plays a role in the regulation of hemostasis by inactivating factors Va and VIIIa in the coagulation cascade.Protein S is a non-enzymatic cofactor for activated protein C–mediated inactivation of factor VIIIa and Va. In addition, protein S may have activated protein C–independent anticoagulant activity. Aim of study:To evaluate protein S&C levels in thalassemic patients &its relation to blood transfusion .Methods: the study included 80 subjects divided into two groups: Case group included 60 patients who were a known cases of transfusion dependent B-thalassemia and control group included 20 participants who were healthy and matched in age and gender with case group. Patients with other forms of hemolytic anemia like sickle thalassemia, who suffering from severe hepatic or cardiac dysfunction, those with other hemoglobinopathies, were excluded from the study. Plasma protein S and C Ag were calculatedin both patient groups and in control group by ELISA.Results: Plasma protein C was significantly lower in patients with splenectomy in comparison with patients without splenectomy.Protein C and S were significantly lower in patients with non-frequent than in patients with frequent blood transfusion. There was significant positive correlation between plasma protein C and protein S levels.Conclusion: Patients with thalassemia major have lower level of protein C and protein S than non-thalassemic patient.Frequency of blood transfusion can affect level of protein C & protein S. Splenoctomized patients have lower levels of protein C and S than non-splenoctomized.

Genetic risk assessment and haemoglobinopathy counselling: two case studies

Background The author works as an antenatal and newborn (ANNB) screening coordinator in a hospital designated as an area of low prevalence for sickle cell and thalassaemia (SCT). As such, the opportunity for an ANNB coordinator to gain competency in prenatal counselling of individuals with SCT is limited. Method Two case studies are used to demonstrate social, cultural and ethical issues arising from counselling individuals with SCT. Findings Information regarding genetic risk and haemoglobinopathy status can be threatening for individuals and families, as well as transforming, depending on the context in which information is provided.

Newborn Sickle Cell and Thalassaemia Screening Programme: Automating and Enhancing the System to Evaluate the Screening Programme.

Good information is needed to demonstrate that a screening programme is meeting its objectives, to measure performance against standards and to ensure that action is taken if standards are not met. In 2010, the NHS Sickle Cell and Thalassaemia (SCT) Screening Programme established a process to collect data on the main outcome measures for newborn babies. In 2016, a review identified that data completeness and quality relied on manual processes and there was widespread dissatisfaction amongst data providers due to duplication of data entry, poor feedback and lack of oversight of the baby to ensure safe handover from screening into treatment services. Using an Agile service design process and following the Government Digital Service Model, the SCT Screening Programme worked in close collaboration with users, wider stakeholders and system suppliers to design and build a new automated system. The new system ensures that the screening programme can fulfil its duty to evaluate the effectiveness of the programme, whilst pleasing the users and enhancing safety. User experience must be central to design and ongoing development to ensure that a new IT system is fit for purpose and adopted by users.

Cholelithiasis in patients with paediatric sickle cell anaemia in a Saudi hospital.

ObjectiveSickle cell disease is one of the most common inherited hemoglobinopathies in the world. Chronic haemolysis predisposes individuals to the development of bilirubinate cholelithiasis, which can be asymptomatic or can result in cholecystitis, choledocholithiasis, cholangitis, and gallstone pancreatitis. We aimed to determine the prevalence of cholelithiasis and associated gallstone disease among patients with paediatric sickle cell disease in a Saudi hospital.MethodsThis retrospective study was conducted among all patients aged between 2 and 18 years. We reviewed the medical records of patients diagnosed with sickle cell anaemia. Mean and standard deviation were calculated for quantitative variables, and the Student t-test was used to compare means. The chi-square test was used to assess those risk factors possibly associated with cholelithiasis. A P-value of ≤0.05 was considered statistically significant.ResultsApproximately 75% of participants developed cholelithiasis (27.5%) at a mean age of 6.9 ± 3.4 years. The frequency of cholelithiasis was significantly higher with increasing age (40.8% in participants 12 years and older) and among those with high levels of haemoglobin S (Hb S) and mean corpuscular volume (MCV). Moreover, cholelithiasis was more frequent among males than females, Saudis than non-Saudis, and in those with sickle cell disease than in those with sickle thalassemia. However, these differences were not statistically significant.ConclusionIn this study, the prevalence of cholelithiasis among children with sickle cell anaemia was found to be high. This association was significantly increased with age and high levels of MCV and Hb S.

Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015.

To describe the prevalence of hemoglobinopathies in the Brazilian adult population, according to laboratory tests from the National Health Survey. A descriptive study was carried out with National Health Survey laboratory data collected between 2014 and 2015. The hemoglobinopathies test was performed using the High Performance Liquid Chromatography method. The results of the individual tests were interpreted as providing normal, homozygous or heterozygous results for S, C and D hemoglobin, in addition to other possible hemoglobinopathies. Prevalence of hemoglobinopathies according to gender, skin color, region, age and schooling was estimated. Hemoglobinopathies were present in 3.7% of the population. The main ones were the sickle cell trait (2.49%), thalassemia minor (0.30%) and suspected thalassemia major (0.80%). In relation to the sickle cell trait and suspected thalassemia major, there was a statistically significant difference for the skin color variable (p<0.05). The prevalences found for sickle cell trait according to skin color was: 4.1% among dark-skinned blacks, 3.6% among light-skinned blacks, 1.2% among whites, and 1.7% among others. The most prevalent hemoglobinopathies were the sickle cell trait and minor thalassemia, and were predominate among light- and dark-skinned black people. The study helps in identifying hemoglobinopathies and in genetic counseling in pre-conception.

Reliability of the current newborn screening action value for beta thalassaemia disease detection in England: A prospective study.

Beta thalassaemias are a group of hereditary red cell disorders resulting in a reduced or absent production of the main adult haemoglobin, adult haemoglobin. In England, the NHS Sickle Cell & Thalassaemia Screening Programme recommends reporting newborn beta thalassaemia disease as an incidental finding when detected whilst screening for sickle cell disease. The current action value to initiate further investigations is 1.5% adult haemoglobin, using high-performance liquid chromatography or capillary electrophoresis. We examined the reliability of this action value. A 44-month country-wide prospective study using data from 13 newborn screening laboratories in England. There were 81 cases reported with an adult haemoglobin of 1.5% or less at first-line screen, of which nine were lost to follow-up. The six false-positive results were all of 32 weeks' gestation or less. Of the 66 true-positives, 36 had confirmatory molecular results (11 of these cases also have results from tandem mass spectrometry), 19 had clinical confirmation and 11 had the results of both parents available which were consistent with the screening result. There was one false-negative, a confirmed beta thalassaemia major case with an adult haemoglobin of 1.7%, above the action value at first-line screen but known to be at risk from parental results and therefore referred into clinical care by the laboratory. This study demonstrates a positive predictive value of 91.7%, with a specificity of 99.9% and a sensitivity of 98.5%. These results confirm the reliability of the current action value.

Renal Complications of Sickle Cell Syndrome in Southern Iran

Background: In spite of many reports on sickle cell disease, to our knowledge frequencies of nephrologic complications are not well defined especially in sickle thalassemia. The aim of this study was to assess the nephrologic complications of sickle cell syndrome. Methods: This is a cross sectional study, including all of the patients with sickle cell syndromes (97 cases) in hematology-oncology clinics of Shiraz University of Medical Sciences. A complete history taken and physical examination was performed. Blood and urine samples were sent for different tests including micro albuminuria and Cystatin C to measure glomerular filtration rate. Results: Ninety seven patients with mean age of 8.5 ± 3.4 years (55.4% males) were divided into three groups; 30 cases with sickle cell disease, 31 patients with sickle cell trait, and 36 cases with sickle thalassemia. Enuresis was present in 20 (22.9%) patients > 5 years. Significant proteinuria was not observed, but micro albuminuria was found in 14 (14.4%) patients. GFR was in normal range when calculated with creatinine clearance, but glomerular hyper filtration was present in 5.2% by Cystatin C formula. Mean serum creatinine was in low normal range (0.5 ± 0.1) but mean serum Cystatin C (0.9 ± 0.1) was higher than the normal range especially in Sβ patients (P = 0.023). Conclusions: In contrast to other reports, at least in the first two decades of life significant renal complications including renal failure and proteinuria were unusual in our patients with sickle cell syndrome.

Long Term Outcome of Splenectomy in Pediatric Patients with Non-Malignant Hematological Diseases: Four Decades of Follow up

Elective splenectomy in childhood can ameliorate the clinical manifestations of non-malignant hematological diseases such as beta-thalassemia, hereditary spherocytosis and chronic immune thrombocytopenia. The advantages however, must be weighed against possible adverse effects. The incidence of infectious complications post splenectomy has decreased as a result of the introduction of novel vaccinations and antibiotic prophylaxis, however this depends on patient compliance. The risk of thromboembolism appears to be related to the underlying diagnosis, although the exact long-term risk has not been well documented. There is a paucity of reports describing large cohorts and long term follow-up of splenectomized hematological patients. We present herein four decades, comprising 1652 patient years, of follow-up of patients who underwent splenectomy in childhood for non-malignant hematological diseases, evaluating the risk of infection and thromboembolic complications.Medical records were screened for the diagnosis of splenectomy among patients previously or currently treated in our pediatric hematology clinic. Demographic, clinical and laboratory data, including the diagnosis, age at time of surgery, infectious and thrombotic complications were recorded. Bacterial infection was defined as positive blood cultures taken due to febrile illness. Thrombotic events included venous thrombosis diagnosed by appropriate imaging. For patients lost to follow up, a telephone follow-up visit was performed using a brief questionnaire focusing on the complications of interest.One hundred and four (104) patients underwent splenectomy between 1974-2015 for the diagnoses of beta-thalassemia major (TM)(33), beta-thalassemia intermedia (TI)(7), sickle-thalassemia (ST)(4), hereditary spherocytosis (HS)(42) or immune thrombocytopenia (ITP)(18). The follow-up period encompasses a total of 1652 years (mean=16, range=1-40 per patient). Mean age at splenectomy was 11.4 years (0.5-25). Vaccinations according to the recommended protocol at time of surgery were administered to 98% of patients. Forty-four bacterial infections occurred in 21 patients. Twenty four percent of the first infections occurred in the first year post-splenectomy, while 67% were within five years post-splenectomy. Only 1 of 7 reported deaths was due to sepsis, in a ST patient. Eight thrombotic events occurred in the cohort, 7 among TM patients with central venous lines (CVL) and 1 case of a postoperative portal vein thrombosis (PVT) in a patient with HS. In univariate analysis, CVL and thalassemia diagnoses were each predictive for both infectious and thrombotic complications (p<0.001). However, in multivariate logistic regression, only the presence of CVL maintained significance (p<0.001).Our study of 104 patients with 1652 years of cumulative follow-up shows an extremely low risk for infectious and thrombotic complications: 1.3 and 0.5 per 100 years at risk, respectively. Only one patient each among the ITP and HS groups developed bacterial infection and the only thrombotic event in a non-thalassemic patient was an immediately post splenectomy PVT in a patient with HS. The majority (19/21) of infections occurred in thalassemic patients, 63% of which had a CVL. Thrombosis beyond the post-operative period occurred exclusively among thalassemic patients with CVL. Infection occurred primarily within 5 years after splenectomy and was fatal in only 1 case.Splenectomy in pediatric patients with non-malignant hematological diseases is a safe procedure with minimal infectious and thrombotic complications particularly among patients with HS or ITP. Abiding by the pre-splenectomy vaccination guidelines for all patients and prudent use of CVLs in splenectomized thalassemic patients should contribute to minimizing long term complications. DisclosuresNo relevant conflicts of interest to declare.