Relation between glutathione S-transferase genes (GSTM1, GSTT1, and GSTP1) polymorphisms and clinical manifestations of sickle cell disease in Egyptian patients

Abstract

Objectives

Clinical manifestations of sickle cell disease (SCD) result from sickling of Hb S due to oxidation, which is augmented by accumulation of oxygen-free radicals. Deficiencies in normal antioxidant protective mechanism might lead to clinical manifestations of SCD like vaso-occlusive crisis (VOC) and acute chest syndrome (ACS). The glutathione system plays an important role in the removal of endogenous products of peroxidation of lipids, thus protecting cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphisms of glutathione S-transferase (GST) genes is expected to increase the severity of SCD manifestations. This report describes a case control study aimed at studying the ethnic-dependent variation in the frequency of GST gene polymorphisms among participants selected from the Egyptian population and to find out the association between GST gene polymorphisms and the severity of SCD manifestations.

Methods

We measured the frequency distribution of the three GSTs gene polymorphisms in 100 Egyptian adult SCD patients and 80 corresponding controls. GSTM1 and GSTT1 genotypes were determined by multiplex polymerase chain reaction (PCR). GSTP1 genotyping was conducted with a PCR-restriction fragment length polymorphism assay.

Results

The GSTM1 null genotype was significantly associated with ACS and VOC (P = 0.03 and 0.01, respectively). The GSTT1 null genotype was associated with significantly increased requirement of blood transfusion (P = 0.01). Absence of both GSTM1 and GSTT1 genes was significantly associated with pulmonary hypertension (P = 0.04). The non-wild-type GSTP1 polymorphism was not associated with clinical manifestations of SCD.

Discussion

Some GST gene polymorphisms were significantly associated with the worsening of the clinical manifestations of SCD.     

Association between endothelial dysfunction and otoneurological symptoms in children with sickle cell disease

Objective: To evaluate the association between endothelial dysfunction and otoneurological symptoms and vaso-occlusive phenomena in children with sickle cell disease (SCD).

Methods: Cross-sectional study with 54 children, aged between 6 and19 years of age, of whom 28 had genotype SS and 26 apparently healthy (AA genotype) whose parents or guardians, or the children themselves, filled out a questionnaire designed to assess their otoneurological symptoms. All the individuals were submitted assessment of endothelial function by flow-mediated dilation (FMD) percentage with reactive hyperemia of brachial artery Doppler.

Results: Otoneurological symptoms (tinnitus and/or vertigo) predominated in the SCD group (46.4 vs. 15.4%; p?=?0.006). A negative correlation was observed between FMD percentage and time of evolution of vertigo SCD (r?=??0.432; p?=?0.022) and the linear regression analysis demonstrated that for every reduction in FMD percentage there was an increase in time of evolution of vertigo of 1.79 months (β?=??1.79; p?=?0.022). The positive correlation between episodes of painful crisis and time of evolution of vertigo (r?=?0.3; p?=?0.04).

Discussion: The presence of vascular endothelial damage in the labyrinthine artery in patients with SCD is capable of compromising the semicircular canals, shown by clinical expression of otoneurological symptoms, such as vertigo. In the present study, an association was observed between endothelial dysfunction with otoneurological symptoms and otoneurological symptoms and vaso-occlusive phenomena in SCD.     

GSTT1 (rs4025935) null genotype is associated with increased risk of sickle cell disease in the populations of Tabuk—Northwestern region of Saudi Arabia

Background: Glutathione system plays an important role in the protection of cells and tissue against damage from oxidative stress. Impairment of the glutathione system due to genetic polymorphism of GST genes may increase the risk and severity of sickle cell disease (SCD). Present study was, therefore, undertaken to examine the relative impact of the genetic polymorphism of GSTT1 and GSTM1 (rs4025935 and rs71748309) on susceptibility and hematological aspects of the patients with SCD.

Methods: Present study included 100 patients with SCD and 200 healthy controls from northwestern region of Saudi Arabia. GSTM1 and GSTT1 (rs4025935 and rs71748309) genotypes were investigated by using single-tube multiplex PCR technique.

Results: It was observed that patients with SCD possessed significantly higher frequency of GSTT1 null genotype (26%) than healthy controls (15%), (P?=?0.00001). Compared to the presence of GSTT1 genotype, the OR for the GSTT1 null genotype were estimated to be 4.3 (2.17–8.64, P?=?0.00001). However, such association was not observed with respect to the presence of GSTM1 null genotype. In addition, it was observed that SCD in patients with GSTT1 genotype, the mean percentage levels for HbF and HbS were 0.48 and 35.4%, respectively; however, among SCD patients with GSTT1 null genotype, the mean percentage levels were significantly higher 1.62% (P?=?0.004) and 39.38% (P?=?0.02), respectively.

Conclusion: GSTT1 null genotype is significantly associated with increased risk of SCD among the population of northwestern region of Saudi Arabia. In addition, it may be one of the important factors responsible for hematological manifestations of SCD.     

DNA array analysis for red blood cell antigens facilitates the transfusion support with antigen-matched blood in patients with sickle cell disease

Background  Blood samples from patients with sickle cell disease (SCD) present to transfusion service with numerous antibodies, making the searching for compatible red blood cells (RBC) a challenge. To overcome this problem we developed an effective strategy to meet needs of supplying RBC-compatible units to SCD patients using DNA arrays.
Methods  We selected DNA samples from 144 SCD patients with multiple (receiving > 5 units) transfusions previously phenotyped for ABO, Rh(D, C, c, E, e), K1, Fy^a and Jk^a. We also selected DNA samples from 948 Brazilian blood donors whose ABO/RhD phenotype matched that of the patients. All samples were analysed by DNA array analysis (HEA Beadchip^TM, Bioarray Solutions) to determine polymorphisms associated with antigen expression for 11 blood group systems (Rh, Kell, Kidd, Duffy, MNS, Dombrock, Lutheran, Landsteiner-Wiener, Diego, Colton, Scianna); and one mutation associated with haemoglobinopathies.
Results  Based on genotype results we were able to predict phenotype-compatible donors needed in order to provide compatible units to this group of patients. Based on their ABO/Rh phenotype we were able to find in this pool of donors compatible units for 134 SCD patients.
Conclusion  Blood group genotyping by DNA array contributes to the management of transfusions in SCD patients by facilitating the transfusion support with antigen-matched blood. It has the potential to improve the life of thousands of SCD-transfused patients by reducing mortality due to transfusion reactions and immunization.     

Is Pica under-reported in children with sickle cell disease? A pilot study in a Belgian cohort

Abstract

Background

For centuries, writers have recorded their observations on pica. Nevertheless the association of pica with sickle cell disease (SCD) was poorly documented.

Methods

Cross-sectional evaluation performed on SCD children and caregivers attending the outpatient clinic who were invited to complete questionnaires assessing behavior of pica.

Results

Out of 55 sickle cell children, 31(56.4%) reported practicing pica regularly. Substances ingested by patients covered a broad spectrum. Compared with the non-pica group, subjects who reported pica were younger and had lower hemoglobin (8.3 g/dl (7.6–9.7) vs. 9.1 g/dl (7.9–10.5): P < 0.01). The level of ferritin, zinc, copper, and lead was similar between the pica and non-pica groups (P > 0.05).

Discussion

In this series, there are many substances consumed by SCD children and adolescents, and we did not find an occurrence of similar substances among this select group. Pica children were younger and more anemic than non-pica patients.

Conclusion

This study suggests that pica remains an unknown and under-reported clinical problem in children with SCD and seems to be related to the severity of anemia. The next step of this project aims to clarify causal mechanisms for pica and its association with SCD in a larger population.     

CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients

Objectives

To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity.

The role of rs1984112_G at CD36 gene in increasing reticulocyte level among sickle cell disease patients

Aims and background: Mediators of adhesion become a potential new target for pharmacological therapy to struggle the complications of sickle cell disease (SCD). Several mechanisms for increased adherence have been postulated and the well-studied are CD36 and VLA4 which encoded by ITGA4. Herein, we sought to determine whether one polymorphism of CD36 namely: rs1984112 and three exons of ITGA4 (4, 5, and 6) are implicated in hemolytic status and clinical events among SCD Tunisian patients.

Material and methods: This study enrolled 99 unrelated Tunisian subjects (63SS and 36Sβ). All SCD patients are children (less than 16 years old). The rs1984112 and the ITGA4’s exons 4, 5, and 6 were analyzed for all subjects by PCR/sequencing. The association of each genotype found with both clinical complications and hemolytic status was performed using t-test. Clinical events studied included vaso-occlusive crisis (VOC), osteonecrosis, stroke, frequent infection, priapism, and acute syndrome.

Results: The results show that rs1984112_G allele at CD36 gene revealed to be associated with higher levels of reticulocyte count (p?p?=?0.051). No association between rs1984112_G allele and the clinical severity of SCD were found. Mutational screening of exon 4, 5, and 6 of ITGA4 gene revealed absence of mutated variant.

Conclusion: Our results are similar to those found in Portuguese population which reported the role of rs1984112_G in increasing reticulocyte level among SCD patients. Consequently, the rs1984112_G of CD36 could be considered as a reliable biomarker for predicting patients at high risk for vascular occlusions and thus, allows earlier and more effective therapeutic management.     

Relationship between the clinical manifestations of sickle cell disease and the expression of adhesion molecules on white blood cells

BACKGROUND: The severity of sickle cell disease (SCD) increases with leukocyte count. The biological basis could be that leukocyte adherence to vascular endothelium mediated by adhesion molecules (AMs) facilitates vaso-occlusion, the basic pathological process in SCD. OBJECTIVE: To find out if there is a relationship between expression of AMs by leukocytes and the clinical manifestations of SCD. METHODS: Flow cytometry was used to study the relationship between leukocyte AM expression and disease manifestations in 100 patients with homozygous (HbSS) sickle cell disease and 34 genotype HbAA controls. The effect of hydroxyurea therapy on AM expression was also examined. We excluded HbSS patients with any other disease, pregnancy in the previous 3 months, or Haemogloben F (HbF) > or = 10%. RESULTS: Patients with complications of SCD showed high expression of alphaMbeta integrin by the neutrophils; and l-selectin by lymphocytes and neutrophils (P < 0.03). CD18 was highly expressed by neutrophils in patients with sickle nephropathy (P = 0.018), and l-selectin by lymphocytes in those with stroke (P = 0.03). Monocyte l-selectin increased in sickle cell crisis relative to steady state (P = 0.04). Expression of alphaLbeta2 integrin by neutrophils, monocytes, and lymphocytes decreased within a month of hydroxyurea therapy (P < 0.05), with symptomatic improvement in the patients and no more than 3.3% rise in HbF level. CONCLUSIONS: The findings suggest that in SCD (1): High steady-state expression of alphaMbeta2 integrin and l-selectin by leukocytes predisposes to severe manifestations. (2) Increased leukocyte AM expression above steady-state levels could be important in the genesis of crisis. (3) The early symptomatic improvement that follows hydroxyurea therapy is mediated via mechanisms independent of increased HbF, and may involve reduced AM expression in leukocytes. (4) Other treatment modalities that reduce leukocyte AM expression might also confer clinical benefit.     

Renal function in adult Jamaicans with homozygous sickle cell disease

Abstract

Objectives

As populations with sickle cell disease (SCD) live longer, it is likely that the burden of renal dysfunction will be an increasing challenge for patients. In this study, we aim to determine the prevalence of renal dysfunction and its possible predictors in persons with SCD.

Methods

Ninety-eight patients with the homozygous SCD (SS disease;55 females, 43 males; mean age 34 ± 2.3 years) in their steady state had measurements of glomerular filtration rate (GFR) using 99mTc-DTPA nuclear renal scan, serum creatinine, and urinary albumin: creatinine ratio. Other haematological and biochemical measurements and data on clinical events were completed for each individual.

Results

Chronic kidney disease (CKD) stages 3 and above was present in 6% of the study population, and 65.3% had albuminuria. Hyperfiltration occurred in 24.5% patients with two-thirds having albuminuria as well. Serum creatinine was an insensitive marker of renal dysfunction as started rising after measured GFR fell below 50 mls/min/1.73 m². Multiple regression modelling showed serum creatinine and height to be significantly associated with GFR. Serum creatinine was also significantly associated with albuminuria, and age was not a predictor in any of the models. There was no association with markers of haemolysis.

Conclusion

We conclude that the burden of renal dysfunction is quite high in this young cohort with SS disease. Serum creatinine is a late and insensitive marker of worsening glomerular function, and screening for albuminuria could begin early in life. Longitudinal studies will continue to increase our understanding of pathophysiological mechanisms that lead to CKD in this specific population.     

The super sickling haemoglobin HbS‐Oman: a study of red cell sickling,K+ permeability and associations with disease severity in patients heterozygous for HbA and HbS‐Oman (HbA/S‐Oman genotype)

Studying different sickle cell genotypes may throw light on the pathogenesis of sickle cell disease (SCD). Here, the clinical profile, red cell sickling and K⁺ permeability in 29 SCD patients (15 patients with severe disease and 14 with a milder form) of HbA/S‐Oman genotype were analysed. The super sickling nature of this Hb variant was confirmed. The red cell membrane permeability to K⁺ was markedly abnormal with elevated activities of P_sickle, Gardos channel and KCl cotransporter (KCC). Results were consistent with Ca²⁺ entry and Mg²⁺ loss via P_sickle stimulating Gardos channel and KCC activities. The abnormal red cell behaviour was similar to that in the commonest genotype of SCD, HbSS, in which the level of mutated Hb is considerably higher. Although activities of all three K⁺ transporters also correlated with the level of HbS‐Oman, there was no association between transport phenotype and disease severity. The super sickling behaviour of HbS‐Oman may obviate the need for solute loss and red cell dehydration to encourage Hb polymerisation, required in other SCD genotypes. Disease severity was reduced by concurrent α thalassaemia, as observed in other SCD genotypes, and represents an obvious genetic marker for prognostic tests of severity in young SCD patients of the HbA/S‐Oman genotype.     

Protector effect of α-thalassaemia on cholecystitis and cholecystectomy in sickle cell disease

Objectives: Cholecystitis is one of the complications of symptomatic cholelithiasis responsible for high levels of morbidity of sickle cell disease (SCD) patients. Here, we investigated the possible protective role of single gene deletions of α-thalassaemia in the occurrence of cholelithiasis and cholecystitis in SCD patients, as well as the cholecystectomy requirements.

Methods: The α-globin genotype was determined in 83 SCD patients using the multiplex-polymerase chain reaction and compared with clinical events.

Results: Overall, in 23% of patients, -α^3.7 deletion was found. α-Thalassaemia concomitant to SCD was an independent protective factor to cholecystitis (OR?=?0.07; 95% CI: 0.01–0.66; p?=?0.020) and cholecystectomy requirement (OR?=?0.14; 95% CI: 0.03–0.60; p?=?0.008). The risk of cholelithiasis was not affected by the α-thalassaemia concomitance.

Conclusions: To the best our knowledge, our study is the first to show the protective effect of α-thalassaemia on cholecystitis and cholecystectomy requirements in SCD, which may be due to an improved splenic function.     

Sickle cell disease serum induces NADPH enzyme subunit expression and oxidant production in leukocytes

Abstract

Oxidative stress plays a significant role in sickle cell disease (SCD), contributing to haemolysis, vaso-occlusive processes and endothelial dysfunction. To study the effects that the serum of SCD individuals has on the oxidative state of blood cells, sera were pooled from control individuals, steady-state SCD patients and SCD patients on hydroxyurea therapy (SCDHU), and their effects on markers of oxidative stress and damage in neutrophils isolated from healthy individuals observed. Incubation of control neutrophils, but not platelets nor red blood cells, with SCD serum (10% v/v; 2 hours) significantly augmented their production of reactive oxygen species (ROS). Increased ROS production in SCD serum-incubated neutrophils was associated with increased superoxide anion generation, apoptosis and increased nicotinamide adenine dinucleotide phosphate oxidase subunit expression. Although serum from SCDHU individuals also induced ROS generation in neutrophils, its oxidative capacity appeared to be lower. Results suggest that factors in the serum of SCD individuals contribute to ROS generation and oxidative damage in leukocytes.     

The level of peripheral blood circulating CD34+ cells is higher in acute promyelocytic leukemia patients with adverse prognostic factors

Introduction: The increased flow cytometry enumeration of peripheral blood circulating CD34+ cells in patients with acute leukemia has been found in our previous work. In this study, we also demonstrated that acute promyelocytic leukemia (APL) patients not only had elevated CD34+ cell count, but also had some clinical features.

Methods: Fifty APL patients and 19 healthy volunteers were included in the study. The enumeration of circulating CD34+ cells, cytogenetic subgroup, immunophenotype analysis, and leukemic-related gene mutation detection were performed.

Results: Some APL patients with higher count of CD34+ cells (≤10 × 10⁶/l) usually possessed one or more poor prognostic factors (higher WBCs count, PML/RARa gene complex fusion, chemotherapy-related APL, normal karyotype/complex karyotype abnormalities, CD56/CD34 antigen positive expression, FLT3-ITD positive mutation, myelofibrosis, and marrow necrosis). A cut-off value of 10 × 10⁶/l CD34+ cells may have the power to distinguish APL patients with above adverse clinical prognostic factor from other APL subjects.

Conclusion: The circulating CD34+ cell count appears to increase in some APL patients and a higher CD34+ cell count may be indicative of inferior survival and serve as an adverse biomarker for APL.     

Restless legs syndrome and sleep quality among adult sickle cell disease patients

Objective

The purpose of this study is to determine and compare the prevalence of restless legs syndrome (RLS) between adult patients with sickle cell disease (SCD) and non-SCD anemia.

Methods

This cross-sectional study was conducted from December 2013 to July 2014. Patients with SCD and non-SCD anemia were recruited from a hematology clinic at a large university hospital. Patients with secondary RLS were excluded. Data were collected on demographic features, clinical evaluations, laboratory tests, sleep quality using the Pittsburgh Sleep Quality Index, RLS symptoms using the International Restless Legs Syndrome Study Group Criteria, severity of RLS using the International Restless Leg Syndrome Rating Scale, and daytime sleepiness using the Epworth Sleepiness Scale.

Results

The study sample consisted of 44 patients with SCD and 45 with non-SCD anemia. The two groups were comparable in age, gender, body mass index, smoking habit, and comorbidities. Poor sleep quality was found in 63% of the SCD group compared to 53% of the non-SCD group. The prevalence of RLS among SCD group and non-SCD group was 13.6% (6/44) and 8.8% (4/45), respectively. These differences, however, were not statistically significant, p?>?0.05. Excessive daytime sleepiness was also similar in both groups, with the rate being 20.5 and 17.8% in the SCD and non-SCD groups, respectively.

Conclusion

Our study revealed that poor sleep quality and RLS were both common among adult patients with SCD; however, they did not differ significantly from patients with non-SCD anemia.

     

Sickle cell disease in Madhya Pradesh,Central India: A comparison of clinical profile of sickle cell homozygote vs. sickle-beta thalassaemia individuals

Background and objectives: The clinical manifestation in sickle cell disease (SCD) patients varies from one individual to another due to factors like the presence of alpha-thalassaemia mutation, foetal haemoglobin, and β-globin gene haplotype. The present study enumerates the clinical profile of sickle cell anaemia patients from Central India.

Methods: Seven hundred seventy-six SCD patients from Jabalpur and surrounding districts (Madhya Pradesh) in central India were registered with the sickle cell clinic of NIRTH, Jabalpur. The present study reveals recorded signs and symptoms of genetically confirmed sickle cell anaemia (404) and sickle beta thalassaemia (92) patients.

Results: Majority of the patients were from scheduled caste communities (47.9%) and Gond tribal community (13.8%). Splenomegaly was the most common clinical manifestation observed (71.4%). Overall, 63.5% patients had a history of blood transfusion. The most frequent signs and symptoms observed were Pallor, Icterus, Joint pain, Fever, and Fatigue. Majority of the patients revealed onset of disease prior to attaining the age of 3 years (sickle cell anaemia 44.3% and sickle beta thalassaemia 35.9%). Mean haemoglobin levels among SCA individuals were marginally higher than SBT patients. On the other hand, mean foetal haemoglobin levels among SBT individuals showed the reverse trend. Notably, the present study reports the first incidence of priapism recorded in Central India.

Conclusions: The study revealed a high prevalence of SCD among scheduled caste, backward caste, and tribal communities. Dissemination of study findings, screening, pre-marriage counselling, and pre-natal diagnosis are fundamental to preventing or lowering of birth of sickle cell anaemia children in the affected populations.     

Echocardiographic evaluation of left ventricular diastolic and systolic function in Saudi patients with sickle cell disease

Background and objectivesSickle cell disease (SCD) is a chronic, inherited haemoglobin disorder, associated with recurrent vaso-occlusive and haemolytic crises and chronic tissue ischemia which may adversely affect any organ system. Our objectives were to evaluate the left ventricular (LV) systolic and diastolic functions in Saudi patients with SCD originally from the Eastern Province of Saudi Arabia.Design and settingProspective hospital based echocardiography study on adolescent and adult patients with SCD.MethodsForty-five patients with SCD were recruited for echocardiographic study while 45 patients, matched for age and sex, served as controls. Left and right ventricular dimensions and LV wall thicknesses, LV mass index (LVMI) and LV contractility variables were obtained. Left atrial dimension and volume and pulmonary artery systolic pressure (PASP) were also estimated. We also evaluated parameters of LV diastolic function, including early and late mitral flow velocities (E and A wave respectively), E/A ratio, deceleration time (MVDT), A wave duration (MVA D), LV isovolumic relaxation time (IVRT), and tissue Doppler velocities, such as lateral annular e‘ wave, a‘ wave, e‘/a‘ ratio and E/e‘ ratio.ResultsThere were increases in the LV dimensions, LV volumes, stroke volume, and LVMI of the SCD patients. The preload was increased (LV diastolic volume) and afterload was decreased (low diastolic blood pressure). The LVEF was equivalent, though there was evidence of LV diastolic dysfunction in 24%, and pulmonary hypertension (PH) in 40% of the SCD patients. The mean left atrial volume (LAV) was also increased in the SCD patients.ConclusionLV diastolic dysfunction (heart failure with preserved ejection fraction) and PH may complicate cases of the Arab-Indian haplotype of SCD.     

Challenges in the management of sickle cell disease during pregnancy in Senegal,West Africa

Objectives: The aim of this study was to evaluate the maternal and fetal complications in pregnant patients with sickle cell disease (SCD) and find risk factors of stillbirth.

Method: We conducted a prospective study in pregnant women with SCD. Demographic characteristics, maternal and fetal morbi-mortality, and outcome of pregnancies were described. Risk factors of fetal loss were evaluated by comparing the parameters of the pregnancies that led to a live birth with those interrupted.

Results: We included 70 pregnancies in 58 women with SCD. The average age was 29.3 years. The average gestational age at the start of follow-up was 13 weeks. The occurrence of acute complications was significantly higher during pregnancy compared to the year before (p?p?Conclusion: Pregnancy in SCD was associated with a high maternal morbidity and stillbirth. Nulliparity, high leucokocytes or platelet count were identified as risk factors of fetal loss.     

A Toll-like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

Despite adequate immunization and penicillin prophylaxis, bacterial infections remain a leading cause of morbidity and mortality in patients with sickle cell disease (SCD). Besides hyposplenism, inflammatory and genetic factors might modulate their susceptibility to bacterial infections. We performed a candidate gene association of single nucleotide polymorphisms (SNPs) located in Toll-like receptor (TLR) genes, encoding prominent molecules for innate immune responses, with the occurrence of bacterial infections in patients with SCD. A cohort followed in centres in Brazil, France and Senegal (n = 430) was divided in two groups: patients who presented at least one episode of bacterial infection (n = 235) and patients who never had bacterial infections (n = 195). There were no differences in gender or age distribution among the groups. The frequency of the TLR2 rs4696480 TA genotype was significantly lower in the infected group (50% vs. 67%, odds ratio [OR] = 0·50, 95% confidence interval [CI] 0·34–0·75, P < 0·001), and the TT genotype was significantly higher in the infected group (15% vs. 5%, OR = 3·18, 95% CI 1·53–6·61, P < 0·001). Previous reports demonstrated higher secretion of inflammatory factors in cells from AA individuals, lower occurrence and severity of immune diseases in T carriers. The rs4696480 TA genotype might stand between deleterious effects of over inflammatory response (AA genotype) and inefficient responses (TT genotype) to infectious agents in SCD settings.     

Epidemiological,clinical, and severity characterization of sickle cell disease in a population from the Brazilian Amazon

Objective/backgroundSickle cell disease (SCD) is a chronic inflammatory condition caused by a point mutation in the HBB gene. Here we characterized the clinical presentation of SCD in a population from Amazonas State in northern Brazil, in order to evaluate whether the higher Amerindian ancestry observed in this relatively isolated geographic region would influence the clinical presentation of SCD.MethodsThis was a cross-sectional study characterizing the clinical presentation of SCD patients registered at HEMOAM, Amazon, Brazil. Data were obtained using a structured questionnaire, and by a review of the medical records.ResultsOf the 236 SCD patients listed in the historical records, 122 were included in this study. The median age was 15 years, with a male to female ratio of 52:70. The population was characterized by a high level of socioeconomic vulnerability, with only 2.1% presenting a family income above five minimum wages. Homozygous HbS (SS) was the most prevalent form of SCD (89.7%), and the diagnosis of SCD was performed in the context of complications in 92.3% of patients. The median frequency of vaso-occlusive crisis in the past 12 months was 2 (0–10). Using a validated clinical severity score based on clinical and laboratory data, no significant difference could be observed when compared to other populations.ConclusionOur results represent the first comprehensive characterization of epidemiological, laboratorial, and clinical data of SCD in the region of the Brazilian Amazon. Despite the higher contribution of Amerindian ancestry previously demonstrated in this region, the main clinical characteristics of SCD seem similar to those reported in other populations.     

Dyspareunia is associated with chronic pain in premenopausal women with sickle cell disease

Objectives: Pain is common in women with sickle cell disease (SCD), but the prevalence of dyspareunia in this unique patient population is unknown. In this study, we sought to determine whether chronic pain is associated with an increased prevalence of dyspareunia in premenopausal women with SCD.

Methods: A cross-sectional study of premenopausal women with SCD was systematically assessed for symptoms of dyspareunia and chronic pain using a standard questionnaire. These results were correlated with each subject's clinical pain phenotype determined by a review of the patient's electronic medical record.

Results: Ninety-one premenopausal women with SCD were examined. Thirty-two percent of the women reported dyspareunia. Women with dyspareunia were more likely to have a history of chronic pain (90% versus 61%, p?=?.006), report more pain days per week (median (interquartile range): 6 (4–7) vs. 3 (0–7), p?=?.005)), and had a higher oral morphine equivalent dose (145 (45–226) mg vs. 60 (9–160) mg, p?=?.030). Using a multivariable classification tree analysis, number of days of pain experienced per week was an important predictor of dyspareunia (p?=?.001).

Conclusion: Dyspareunia is common in women with SCD, and more common in women with SCD and chronic pain. Providers should assess women with SCD for dyspareunia, especially those with a chronic pain syndrome.