Sickle Cell Trait Group Research Articles

Evaluation of the Possible Pathophysiological Role of Redox Status in Patients with Sickle Cell Anemia

Abstract BACKGROUND: The disease of sickle cell anemia (SCA) is an inherited blood disease that causes several complications, and oxidative stress (OS) may play a very important role in its complications and pathophysiology. OBJECTIVE: The aims of the study is to evaluate the possible pathophysiological role of some antioxidant and oxidant biomarkers within SCA patients and to evaluate the correlation of OS and atherogenic index of plasma (AIP) to predict the cardiovascular risk in SCA subjects. MATERIALS AND METHODS: A case–control research includes three study groups: SCA patients, sickle cell trait (SCT) subjects, and healthy controls (HCs). All study groups were evaluated for their serum catalase (CAT), serum superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) as well as plasma triglycerides and high-density lipoprotein cholesterol. Data were collected, tabulated, and statistically analyzed using (SPSS) version 31 program. The frequencies, relative frequencies, and means were obtained as descriptive methods. The associations among parameters were obtained using the Chi-square statistical method. RESULTS: The results revealed significantly lower levels of serum SOD and GPx among sickle cell disease (SCD) and SCT subjects than the HCs, whereas the inverse findings were reported for CAT and AIP. However, the MDA results revealed a significantly higher level in SCD patients compared to SCT and HC. Furthermore, the levels of SOD and MDA were positively associated in all study groups, and the levels of GPx and MDA were negatively correlated in SCD and SCT groups. The AIP was positively correlated with MDA in the SCT group and negatively correlated with CAT in the SCD group. CONCLUSIONS: The conclusion of the study indicated the presence of an OS and antioxidant compensatory status in patients with SCD and the SCT subjects. The altered biomarkers in SCA patients made it clear that the impairment and generation of OS in this disease, as well as antioxidant biomarkers, are contributory factors toward cellular redox homeostasis. This addressed the aim of the study.

COVID-19 outcomes in patients with sickle cell disease and sickle cell trait compared with individuals without sickle cell disease or trait: a systematic review and meta-analysis

Clinical manifestations and severity of SARS-CoV-2 infection in individuals with sickle cell disease (SCD) and sickle cell trait (SCT) are not well understood yet. We performed a systematic review and meta-analysis to assess COVID-19 outcomes in individuals with SCD or SCT compared to individuals without sickle cell disease or trait. An electronic search on PubMed, Embase, and Cochrane Library was performed on August 3, 2023. Two authors (IFM and ISP) independently screened (IFM and ISP) and extracted data (IFM and ILC) from included studies. Main exclusion criterion was the absence of the non-SCD/SCT group. Exposure effects for binary endpoints were compared using pooled odds ratio (OR) with 95% confidence intervals (CI). I2 statistics was used to assess the heterogeneity and DerSimonian and Laird random-effects models were applied for all analyses to minimize the impact of differences in methods and outcomes definitions between studies. The overall quality of evidence was assessed using the GRADE system. Review Manager 5.4 and R software (v4.2.2) were used for statistical analyses. Registered with PROSPERO, CRD42022366015. Overall, 22 studies were included, with a total of 1892 individuals with SCD, 8677 individuals with SCT, and 1,653,369 individuals without SCD/SCT. No difference in all-cause mortality was seen between SCD/SCT and non-SCD/SCT (OR 1.18; 95% CI 0.78-1.77; p=0.429; I2=82%). When considering only studies adjusted for confounders (8 studies), patients with SCD/SCT were shown to be at increased risk of death (OR 1.86; 95% CI 1.30-2.66; p=0.0007; I2=34%). No significant difference was seen between individuals with SCD and SCT (p=0.863). The adjusted for confounders analysis for hospitalisation revealed higher rates for the SCD (OR 5.44; 95% CI 1.55-19.13; p=0.008; I2=97%) and the SCT groups (OR 1.31; 95% CI 1.10-1.55; p=0.002; I2=0) compared to the non-SCD/SCT population. Moreover, it was significantly higher for the SCD group (test for subgroup difference; p=0.028). Our findings suggest that patients with SCD or SCT may present with a higher mortality and hospitalisation rates due to COVID-19 infection. None.

Levels of inflammatory markers are differentially expressed in sickle cell anemia and sickle cell trait.

Although sickle cell anemia (SCA) is related to inflammation, the profile of inflammatory markers in sickle cell trait (SCT) is poorly studied. This is a cross-sectional study of inflammatory biomarkers carried out involving adults with SCA in steady state, SCT and controls. The SCA group had higher levels of lactato dehydrogenase, IL-1β, IL-6, IL-10, and tumor necrosis factor alpha than the others, while the SCT group had similar levels to control group. In addition, SCA group had lower IL-8/IL-10 and soluble triggering receptor expressed on myeloid cells-1/IL-10 ratios. These findings indicate that individuals with SCT do not have a chronic inflammatory profile and reinforce that cytokines are involved in the maintenance of the inflammatory state in SCA.

Effect of Sickle Cell Trait on the Treatment Response of Individuals Infected with Human Immune-Deficiency Virus (HIV)

Background: Sickle cell disease is of public health importance and comes with systemic organ complications that can cause long-term disabilities and early death.
 Aim: This study was to determine the effect of co-existence between sickle cell gene (HbS) and HIV infection in a Lagos population.
 Methods: The study was conducted at the anti-retroviral (ARV) outpatient clinic of the Nigerian Institute of Medical Research (NIMR), Yaba, Lagos. It is a cross-sectional cohort study of 292 adult HIV- positive patients who were enrolled for treatment and support in the centre between the year 2004-2015. A review of case notes and database was done to extract haematologic, immunologic, virologic and clinical information of the patients. The enrolled participants were invited for additional clinical and socio-demographic information using a structured questionnaire. Blood samples were collected and reanalysed to confirm the haemoglobin genotype. Data analysis was performed using SPSS software.
 Results: Out of 292 recruited patients, 274 participants had complete data of which 74.1%, 22.9% and 2.9% were HbAA, HbAS and HbAC respectively. Sickle cell trait (SCT) was found in 25.9% of the participants and there was no record of sickle cell disease (SCD). HbAA participants were found to have a higher viral load (87.5%) at baseline (P < 0.001). For HbAA and SCT groups, treatment response over the years was similar with lower figures seen in SCT.
 Conclusion: It was concluded that lower HIV viraemia in SCT might mean a delay in HIV-1 disease progression and subsequently better quality of life for such patients.

Adverse Pregnancy Outcomes in Sickle Cell Trait: a Prospective Cohort Study Evaluating Clinical and Haematological Parameters in Postpartum Mothers and Newborns.

Sickle cell trait (SCT) is a congenital condition caused by the inheritance of a single allele of the abnormal haemoglobin beta gene, HbS. Carriers of SCT are generally asymptomatic, and they do not manifest the clinical and haematological abnormalities of sickle cell anaemia (SCA). However, there is evidence that they display some symptoms in stressful situations. Pregnancy is a stressful physiological event, and it is not clear if SCT adversely affects pregnancy outcomes, particularly in those from developing countries where people regularly suffer from nutritional insufficiency. This study aims to investigate pregnancy outcomes in Sudanese women with SCT. Subjects and methods: Pregnant women with (HbAS, n=34) and without (HbAA, n=60) SCT were recruited during their first trimester at El Obeid Hospital, Kordofan, Western Sudan. Following appropriate ethical approval and informed consent from the participants, detailed anthropometric, clinical, haematological, obstetric, and birth outcome data were registered. In addition, blood samples were collected at enrolment and at delivery. At enrolment in the first trimester, the SCT group did not manifest SCA symptoms, and there was no difference in the haematological parameters between the SCT and control groups. However, at delivery, the women with SCT, compared with the control group, had lower levels of hemoglobin (Hb, p=0.000), packed cell volume (PCV, p=0.000), mean corpuscular haemoglobin (MCH, p=0.002) and neutrophil counts (p=0.045) and higher mean corpuscular volume (MCV, p=0.000) and platelet counts (p=0.000). Similarly, at delivery, the babies of SCT women had lower birth weight (p=0.000), lower Hb (p=0.045), PCV (p=0.000), MCH (p=0.000), and higher neutrophil (p=0.004) and platelet counts (p=0.000) than the babies of the healthy control group. Additionally, there were more miscarriages, stillbirths, and admissions to the Special Care Baby Unit (SCBU) in the SCT group. The study revealed that SCT is associated with adverse pregnancy outcomes, including maternal and neonatal anaemia, low birth weight, and increased risk of stillbirth, miscarriage, and admission to SCBU. Therefore, pregnant women with SCT should be given appropriate pre-conceptual advice and multidisciplinary antenatal and postnatal care.

Outcomes of Patients With Sickle Cell Disease and Trait After Congenital Heart Disease Surgery

BackgroundSickle cell disease (SCD) is a hemoglobinopathy that can cause multiorgan dysfunction. This study assessed the perioperative outcomes of patients undergoing operations for congenital heart disease who had SCD or sickle cell trait (SCT). MethodsWe performed a retrospective review of patients with SCD or SCT who had records in The Society of Thoracic Surgeons Congenital Heart Surgery Database between 2014 and 2019. The primary outcome was operative mortality. Secondary outcomes included postoperative complications. One-to-one propensity score matching was performed between the SCD and SCT groups and the control group for further analysis. ResultsOur study population consisted of 73, 411, and 36 501 patients in the SCD, SCT, and control groups, respectively. Median (25%-75% interquartile range) age at surgery was 2.8 (0.4-9.7), 0.60 (0.2-3.1), and 0.70 (0.2-6.4) years in the SCD, SCT, and control cohorts, respectively. Operative mortality, surgery duration, cardiopulmonary bypass time, and cross-clamp time were not significantly different among the 3 groups. The SCD group had a higher rate of postsurgical cardiac arrest than its propensity score-matched control group (5.5% vs 0%, P < .05); otherwise, there were no statistically significant differences in the outcomes between the SCD and SCT groups and their respective matched control groups. ConclusionsOperative mortality after cardiothoracic procedures in patients with SCD or SCT appeared similar to our control patients. While these patients may require unique perioperative management, they can undergo cardiac surgery without an observed increase in mortality.

Periodontal Health in Sickle Cell Disease - A Case Control Study

Introduction: A hereditary autosomal recessive condition goes by the name of sickle cell disease. Hemoglobin S polymerization in red blood cells under hypoxic circumstances results in vascular blockage, which is the pathophysiology of sickle cell disease. For the sake of maintaining group homogeneity, participants in the healthy group were either related to or friends of those with sickle cell disease, whereas those in the sickle cell trait group were related to those with sickle cell illness.&#x0D; Materials and Methods: A total of 150 participants were recruited for this research, 43 percent of them were female and 57 percent male. Patients in the control group were on average 30 years old, whereas those in the SCT group were 33 years old, and the average age of patients with SCD was 26. Those with sickle cell trait (SCT) and those with sickle cell disease (SCD) were divided into three categories. Patients were screened and diagnosed with chronic periodontitis using clinical criteria developed at the 1999 International World Workshop for Classification of Periodontal Diseases and Conditions.&#x0D; Results: The SCD, ST, and healthy groups did not vary significantly in terms of clinical indicators such as gastrointestinal (GI), peritoneal (PPD), and caloric (CAL). SCT group PI-1.550.45, GI 1.540.43, PPD-2.170.72 was greater than the mean and standard deviation of the SCD and control groups, but the chi square test revealed it to be non-significantly different.&#x0D; Conclusion: It is possible that patients with the Indian haplotype of SCD, albeit having milder symptoms of the illness, contributed to our conclusion that SCD, SCT patients had no significantly greater periodontal breakdown than healthy people. Although SCD's fundamental pathophysiology raises issues about our knowledge of periodontitis, additional study is needed.

Association between carriers of the G allele of the + 45T> G variant of the ADIPOQ gene (rs 2241766) and the cardiometabolic profile in sickle cell trait

Aimsinvestigate the association between the +45T > G variant of the ADIPOQ gene and the metabolic syndrome (MS) in patients with sickle cell trait (SCT). 33 patients with SCT and 35 control group participated in the study. Lower levels of HDL and adiponectin were observed in patients with G allele and sickle cell trait. There were no differences between the prevalence of MS between the groups and there was no association between the +45T > G variant of the ADIPOQ gene and MS risk allele. Materials and methodsParticipants with and without sickle cell anemia answered a questionnaire, performed anthropometric and laboratory analyzes. They were genotyped for the +45T > G variant of the ADIPOQ gene and evaluated for the presence or absence of metabolic syndrome. The study was approved by the Research Ethics Committee of UNIPAMPA (RS/Brazil). Key findingsThe GG + TG genetic model, it was associated with lower levels of adiponectin and HDL cholesterol in the SCT group. There was no association between the other studied markers and MS. SignificanceFor the first time, an association was demonstrated between the G allele of the +45T > G variant of the ADIPOQ gene and a worse cardiometabolic profile (lower serum concentrations of adiponectin and HDL cholesterol) in patients with sickle cell trait.

Outcomes of Sickle Cell Disorders in COVID-19 Infection: An Institutional Experience

Introduction:With the emergence of the Coronavirus Disease 2019 (COVID-19) as a global pandemic came the concern that it would adversely affect individuals with comorbid conditions. In sickle cell disease (SCD), the apprehension was largely driven by concerns that the disease causes chronic inflammation, organ dysfunction and a prothrombotic state, especially during a vaso-occlusive crisis. Our assumption and hypothesis was that SCD pathology would be exacerbated by SARS CoV-2 infection leading to higher rates of acute chest syndrome (ACS), venous thromboembolism (VTE), more robust inflammatory responses requiring ICU care and increased death rates.Sickle cell trait (SCT) is frequently perceived as a benign condition; however, mounting evidence has shown that severe hypoxia (such as that seen in COVID-19 infection) can trigger sickle-related complication such as VTE, papillary necrosis and splenic infarcts and, in rare cases, ACS. In this retrospective analysis, we aimed to determine if sickle cell disorders (SCD & SCT) would confer poorer outcomes and/or increased mortality due to COVID-19 infection.Methods:Within the MedStar health care system there are 7,551 adult patients with a diagnosis of sickle cell disorder. We performed a retrospective chart review of all patients in the MedStar system with hemoglobinopathy and a lab-verified diagnosis of COVID-19 infection between March 1, 2020 and June 30, 2020. Sixty-one patients met our search criteria with 21 patients admitted to the hospital and 40 patients managed in the outpatient setting. Of the 21 patients admitted: 9 patients had sickle cell disease (Hb SS, Hb SC, Hb SB thalassemia) and 11 patients had sickle cell trait. One patient had HbC disease.Results:Results were analyzed by SCD genotype (Hb SS, Hb SC, Hb SB Thalassemia) versus the presence of a SCT. Due to the small sample size, statistical significance was not met in the variables. In the 21-patient cohort: 76.2% were female (60% of SCD and 90.9% of SCT) and 100% were African American. Median age was 46.5 years in the SCD group and 38 years in the SCT group. Length of stay was 10 days in the SCD group and 6 days in the SCT group. Mean peak white blood cell count and platelet count were significantly higher in SCD group (WBC: 15.1 k/uL vs 7.5 k/uL; p value 0.099. Platelets: 523 k/uL vs 185 k/uL; p value 0.082). Inflammatory markers were more elevated in the SCD cohort: mean Ferritin (915 ng/mL vs 520 ng/mL), mean D Dimer (2.96 mg/L vs 1.07 mg/L) and mean LDH (543 units/L vs 392 units/L). However, mean peak C-reactive protein (CRP) was higher in the SCT group (117.5 mg/L vs 67.7 mg/L). Admission to the intensive care unit (ICU) occurred in 11.1% with SCD & 36.4% with SCT and renal replacement therapy was required in 11.1% with SCD & 28.6% with SCT. Nasal cannula was required in 75% of patients (88.9% of SCD & 57.1% of SCT; p value 0.262) with only one SCT patient requiring intubation and mechanical ventilation whom later died. Two patients with Hb SS developed ACS, one of whom died. One patient with HbSC disease developed ACS and an acute cerebrovascular accident. No VTE or pulmonary embolisms were documented in this cohort.Therapeutic drugs used in the cohort varied, with 43.8% receiving antibiotics (other than Azithromycin), 37.5% receiving Azithromycin and 25% receiving Hydroxychloroquine. None of the patients received convalescent plasma, steroids, tociluzumab, sarilumab or remdesivir. Anticoagulation was used in 93.8% of the patients (13.3% of which were in therapeutic doses).Conclusions:Sickle cell disease diagnosis did not seem to influence response to COVID19 illness when compared to age-matched individuals with SCT. The number of patients with sickle cell disease admitted to the hospital after contracting SAR CoV2 infection was also remarkably low. These findings were, in general, unexpected. Although the inflammatory biomarkers were generally higher in the patients with SCD, more patients with SCT were admitted to the ICU and required renal replacement therapy. The major drawbacks of the study are the small sample size and missing data points (lack of labs, lack of documentation, transfer to another facility) that did not allow us to draw statistical conclusions about the differences in the patients with SCD versus SCT. We were also unable to determine the influence of SCD severity and pre-existing organ complications on outcomes in COVID 19 disease. Additional studies with larger cohorts is warranted.DisclosuresNo relevant conflicts of interest to declare.

An exploratory study of the effects of strenuous exercise on markers of coagulation activation, circulating microparticles, and inflammation in sickle cell trait.

This exploratory study evaluated the effect of intense exercise on biomarkers of inflammation and coagulation activation in subjects with and without sickle cell trait (SCT). Fifteen healthy African American men (18‐35 years, 5 SCT, 10 control) completed a strenuous exercise protocol. Microparticle‐associated prothrombinase and tissue factor activities, as well as soluble VCAM, total white cell and monocyte count increased transiently in all subjects following exercise. In the SCT group, exercise resulted in increased d‐dimer, erythrocyte phosphatidylserine exposure, as well as increased circulating erythrocyte‐ and endothelial‐derived microparticle numbers. These alterations could contribute to exercise‐related complications in people with SCT.

Evaluation of agreement between hemoglobin A1c, fasting glucose, and fructosamine in Senegalese individuals with and without sickle-cell trait.

Fasting glucose (FG) and glycated hemoglobin A1c (HbA1c) perform sub-optimally in people of African origin, especially in individuals with sickle-cell trait (SCT). The purpose of this study was to compare the relationships between HbA1c, FG, and fructosamine in individuals from Senegal with and without SCT. HbA1c, FG, and fructosamine were measured in 203 adults from Senegal (100 control: 45 with type 2 diabetes (T2D); 103 SCT: 51 with T2D). Significant, positive correlations were observed between HbA1c and FG, fructosamine and FG, and fructosamine and HbA1c in both groups. The limits of agreement were inappropriately large in both groups for the Bland-Altman plots of HbA1c and FG (control: -95.97 to 83.97%; SCT: -115.9 to 91.52%), fructosamine and FG (control: -100.6 to 99.89%; SCT: -105.6 to 100.6%), and fructosamine and HbA1c (control: -52.03 to 38.98%; SCT: -88.04 to 71.41%). In both groups, the greatest proportion of subjects were considered above the clinical cut-point for hyperglycemia when fructosamine was used as the criterion (control: 33%; SCT: 44.6%), and the lowest percentage of subjects were classified as over the clinical cut-point when HbA1c was used as the criterion (control: 21%; SCT: 27.7%).Substantial disparities between HbA1c, FG, and fructosamine were observed in both groups, and these differences were exaggerated in the SCT group. Therefore, these three biomarkers should not be considered to be interchangeable measures of glycemic control. These biomarkers should be used thoughtfully, and special care should be taken when using them in individuals with SCT.

Association between Sickle Cell Trait and the Prevalence and Severity of Diabetic Retinopathy.

PurposeTo determine whether Sickle cell trait (SCT) is associated with an increased severity of diabetic retinopathy.MethodsThis was a single center retrospective study case control study of 100 eyes of 100 patients with diabetes mellitus (DM) with SCT (SCT group) and 100 eyes of 100 age-matched patients with DM without SCT (control group). The main outcome measure was the difference in the prevalence of sight threatening DR [here defined as diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR)], between the SCT and control groups. Secondary outcome measures included differences in visual acuity, ocular comorbidities, intraocular pressure, glycemic control as assessed by random blood glucose measurement, diabetes duration, nephropathy, hyperlipidemia and hypertension.ResultsThe SCT group had statistically significantly shorter duration of DM (median [25% quartile] 15 [8.3] years versus 20 [14.7] years, respectively)(P<0.001) and presented with statistically better metabolic control (mean difference 1.6 mmol/l, (95% confidence interval [CI], 0.1–3.3;P = 0.03). The prevalence of PDR and/or DME was significantly lower in the SCT group (58%) compared to the control group, (95%)(P<0.001). The absence of SCT (adjusted odds ratio [AOR] = 24; 95% CI, 8–72; P<0.001) and longer duration of DM (AOR = 1.1 [95% CI, 1.02–1.13]; P = 0.003) were independent predictors of PDR and/or DME.ConclusionsSCT seems to protect against the development and progression of DR. This may have implications for monitoring and screening. Prospective studies are required to confirm this association. If true, this association may indicate an increased blood glucose buffering capacity of abnormal hemoglobin.

Tartrate-Resistant Acid Phosphatase 5b in Young Patients With Sickle Cell Disease and Trait Siblings: Relation to Vasculopathy and Bone Mineral Density.

Bone involvement is a frequent cause of acute morbidity in sickle cell disease (SCD). Tartrate-resistant acid phosphatase 5b (TRACP 5b), a bone resorption marker, is produced specifically by activated osteoclasts. We assessed bone mineral density (BMD) in 30 young patients with SCD and 17 asymptomatic patients with sickle cell trait (SCT) compared with 32 healthy controls and determined TRACP 5b levels in relation to vascular complications. Serum ferritin, alkaline phosphatase (ALP), and TRACP 5b were measured. Echocardiography was performed with assessment of BMD using dual energy X-ray absorptiometry (DXA). The BMD was decreased in patients with SCD compared with SCT and controls (P = .005), with no significant difference between the latter 2 groups. Patients with SCD had higher incidence of bone complications than SCT group and controls (P = .03). The SCD group with abnormal DXA scan had higher ferritin and ALP than normal BMD. Serum TRACP 5b was significantly higher in patients with SCD than SCT and controls (P = .003). The TRACP 5b levels were associated with severe vaso-occlusive crisis (P = .022). Patients treated with hydroxyurea and those on chelation therapy had lower TRACP 5b levels than untreated patients. The TRACP 5b level was positively correlated with lactate dehydrogenase, while there was no relation with ferritin, ALP, or BMD. We suggest that bone complications frequently occur in SCD as reflected by low BMD and high ALP and TRACP 5b. Hemolysis and iron overload may be involved in the occurrence of these complications. The lack of correlation between abnormal DXA scan and high TRACP 5b suggests that bone disease in SCD is multifactorial.

Impact of sickle cell trait on the thrombotic risk associated with non-O blood groups in northern Nigeria.

The non-O blood group is an established risk factor for deep vein thrombosis (DVT), while controversy surrounds the role of sickle cell trait (SCT) as a risk factor for DVT. We hypothesised that if SCT is a risk factor for DVT, individuals with non-O blood groups and SCT (Hb AS) would have a higher risk of DVT than their counterparts with non-O blood groups and normal haemoglobin phenotype (Hb AA). We retrospectively analysed the prevalence of SCT and non-O blood groups among 148 DVT patients with control subjects in order to determine the role of SCT as a risk factor for DVT and its impact on the risk of DVT among patients with non-O blood groups. In comparison with control subjects, DVT patients had significantly higher prevalences of SCT (35.1% vs 27.7%, p=0.04) and non-O blood groups (68.9% vs 45.9%, p=0.02). The odds ratios for DVT due to SCT, non-O blood groups with normal Hb phenotype (Hb AA) and non-O blood groups with SCT (Hb AS) were 1.3, 2.4 and 3.5, respectively. These results suggest that SCT by itself is a weak risk factor for DVT but it has the potential of escalating the DVT risk among patients with non-O blood groups. The combined effects of elevated clotting factors (non-O group effect) and increased clotting factor activation (SCT effect) were responsible for the escalated DVT risk among patients with co-inheritance of non-O blood groups and SCT. Co-inheritance of SCT and non-O blood group is, therefore, an important mixed risk factor for DVT. This should be taken into account when assessing DVT risk profiles of patients in Africa and other parts of the world where the SCT is prevalent.

Overactive bladder in adults with sickle cell disease.

To characterize the prevalence and impact of nocturnal enuresis and overactive bladder (OAB) symptomatology in the adult sickle-cell disease (SCD) population. We performed a single-center, cross-sectional study of adult SCD patients from October 2012 to February 2014, using the validated Pfizer OAB short form questionnaire and brief voiding history surveys. Patient responses and scores were compared to that of controls having normal or sickle cell trait hemoglobin genotypes. A group of 239 SCD patients (116 males, 123 females) were compared with 104 normal and 57 sickle cell trait patients. Seven of 239 (2.9%) SCD patients compared to none of the 161 patients without SCD (P = 0.04) reported current nocturnal enuresis. The median age of nocturnal enuresis cessation was higher in SCD patients (12.0, IQR 9.0-15.0 years) compared to that of both normal (7.5, IQR 6.0-9.8 years) and sickle cell trait (7.5, IQR 6.0-8.8 years) groups (P < 0.0001). Ninety-three of 239 (38.9%) SCD patients compared to 17 of 104 (16.3%) normal and 11 of 57 (19.3%) sickle cell trait had scores indicating OAB symptomatology (P < 0.0001). Patients with SCD had higher OAB symptom severity and lower health-related quality of life (HRQL) scores compared to the normal and sickle cell trait groups (P < 0.0001 and P < 0.0001, respectively). We demonstrate an elevated rate of nocturnal enuresis and OAB symptoms in the adult SCD population. An OAB phenotype may be an under-recognized complication of SCD irrespective of age. Neurourol. Urodynam. 35:642-646, 2016. © 2015 Wiley Periodicals, Inc.

Sickle Cell Trait: Is There an Increased VTE Risk in Pregnancy and the Postpartum?

Blacks are purported to have a higher venous thromboembolism (VTE) risk than whites. We hypothesized that this might be due, in part, to the greater presence of sickle cell trait (SCT) among blacks. We investigated whether the presence of SCT resulted in a higher VTE incidence in a population predisposed to VTE, the pregnant/postpartum women. Methods: Using a mirrored clinical database that prospectively gathered in- and out-patient information for the years 1998–2008, we collected demographic data, including hemoglobin electrophoreses, on all pregnant/postpartum non-Hispanic women who delivered at a large, diverse, urban hospital. We identified those women who developed VTE either while pregnant or postpartum during those 11 years. Charts initially identified as potential VTE cases were subjected to review to ensure accuracy of VTE coding. Results: Of 12,429 women, 679 non-Hispanic SCT black women, 5,465 non-Hispanic Hemoglobin AA (women with HbA as the only hemoglobin present on electrophoresis, with normal amounts of the minor hemoglobins) black women and 1,162 non-Hispanic HbAA white women were included in the analysis. SCT prevalence was high (11.1%) within this black population as compared to 8.3% in the general non-white population. Proportions with VTE were similar for black SCT and black HbAA groups: 0.44% for the SCT group, 0.49% for non-Hispanic black HbAA women. Black HbAA women had a non-significantly higher proportion of VTE than white HbAA women 0.49% vs 0.26% (RR 1.9, 95%CI:0.6,6.3, p = 0.28). Women with VTE were older than those without VTE (32.2 vs. 27.6 years, p = 0.0002) and the majority of VTE occurred postpartum in all groups, and significantly in the HbAA groups. There was no increase in the incidence of pulmonary emboli in the SCT group. Conclusion: In the largest analysis to date, we could not detect a meaningful difference in peripartum VTE incidence between women with and without sickle cell trait.

Cardiovascular autonomic dysfunction in sickle cell anemia

Sickle cell anemia (SCA) is associated to increased cardiac output, normal heart rate (HR), abnormal QT dispersion and lower diastolic blood pressure (DBP). The mechanisms are still unknown. The objective of this study was to test the hypothesis that there is cardiovascular autonomic dysfunction (CAD) in SCA. The secondary objectives were to distinguish the roles of chronic anemia and hemoglobinopathy and to evaluate the predominance of the sympathetic or parasympathetic systems in the pathogenesis of CAD. Sixteen subjects with SCA, 13 with sickle cell trait (SCT), 13 with iron deficiency anemia (IDA), and 13 healthy volunteers (HV) were evaluated. All subjects were submitted to 24h-electrocardiogram (24h-ECG), plasma norepinephrine (NE) measurement before and after isometric exercise (IE), and also Valsalva maneuver (VM), diving maneuver (DV), and tilt test (TT). Baroreflex sensitivity (BRS) was also evaluated. The minimum, average and maximum HR as well as the percentage of bradycardia and tachycardia at 24-h ECG were similar in all groups. NE at baseline and after IE did not differ between groups. The SCA group showed less bradycardia at phase IV of VM, less bradycardia during DV, and also less tachycardia and lower DBP during TT. BRS for bradycardia and tachycardia reflex was decreased in the SCA and SCT groups. In conclusion, 1) there is CAD in SCA, and it is characterized by the reduction of BRS and the limitation of HR modulation mediated by the parasympathetic system; 2) cardiovascular sympathetic activity is preserved in SCA; and 3) hemoglobinopathy is the preponderant ethiopathogenic factor.

Influence of Sickle Cell Trait on the Risk of Venous Thromboembolism In Pregnancy and the Postpartum

AbstractAbstract 1628 Background:Evidence suggests a disparity in the incidence of venous thromboembolic events (VTE) amongst racial groups, with blacks purported to have a higher occurrence of VTE than whites. In contrast, Hispanics and Asians have been observed to have a lower occurrence of VTE. Sickle cell anemia is a known prothrombotic state and recent studies contend that sickle cell trait (SCT) may also predispose to VTE. We hypothesized that SCT might play a role in the increased VTE risk for blacks. To this end, we conducted a study to investigate whether pregnant/postpartum women with SCT have a higher VTE incidence than controls without SCT. Methods:Patient information was obtained using our hospital database spanning the eleven years 1998–2008. All pregnant women seen in our large urban medical center had hemoglobin (Hb) electrophoresis screening on their first clinic visit; demographic data was obtained from the patient at registration. Using prospectively-collected data, three patient cohorts were identified. Group A included women with SCT as identified by %HbS of 30–45% on Hb electrophoresis. To ensure exclusion of patients with sickle cell disease who were post-transfusion, subjects who at any time in their medical record had %HbS >45% were excluded from analysis. HbAA black (Group B) and white (Group C) cohorts were included if %HbA was ≥95.5%. Women who self-identified themselves as Hispanic, multiracial, “declined”, “not available” or “not applicable” were also excluded. VTE cases were identified using ICD-9 codes from hospital, ER or outpatient visit discharges during the pregnancy or postpartum period (294 days before delivery or 56 days after delivery). All charts of VTE indexed cases were reviewed (by SP) to ensure accuracy of reporting. Results:The prevalence of SCT was found to be high (11.1%) in our Group A population as compared to 8.3% in the general pregnant/postpartum non-white population that included Hispanics, multiracial and unavailable individuals. We identified 679 black subjects with SCT, 5465 black subjects with HbAA and 1162 white subjects with HbAA. VTE incidence was 0.44% in Group A (SCT), in 0.49% in Group B (Black AA) and in 0.26% in Group C (White AA). The rate of VTE did not significantly differ between these groups. When patients were included who had been thromboprophylaxed secondary to previous VTEs, the incidence of VTE in Black AA was 0.6%, still not significantly different from the white AA group (p=0.13). Age was a more important factor: patients with VTE were significantly older than non-VTE pregnant patients (mean 32.2 vs. 27.6 years, p=0.0002). As expected, the majority of VTE occurred in the postpartum period (61%). Conclusion:Our results suggest that there is a nonsignificant trend toward a higher incidence of VTE in black HbAA (Group B) as compared to white women with HbAA (Group C) in the pregnant/postpartum period. We could not detect a difference in VTE incidence between black SCT (Group A) and black HbAA (Group B). The role of sickle cell trait as an inherited prothrombotic mutation remains unclear. Even a mild increase in age appears to constitute a prothrombotic risk. However, as VTE remains one of the major causes of maternal mortality, further studies will be needed to better identify risk factors of VTE in pregnancy. Prospective studies identifying such patients may help characterize the true impact of sickle cell trait on venous thromboembolism in pregnancy and postpartum. Disclosures:No relevant conflicts of interest to declare.

Resultados maternos e perinatais em gestações complicadas por doenças falciformes

the aim of this study was to describe perinatal and maternal outcomes of pregnancies complicated by sickle cell disease (SCD), comparing to pregnancies of women with sickle cell trait (SCT). this was a retrospective cohort study, covering the period from March 2001 to April 2008, which included all pregnant women with SCD (n=42) followed up at a university hospital in the Southeast region of Brazil. The maternal and perinatal outcomes were compared to those of pregnant women with SCT (n=56) who were followed up at the same service. SCD-SS was diagnosed in 42 (82.4%) pregnant women and SC in 9 (17.6%). Mean (±SD) maternal age was significantly lower in the SCD group (26.0 years) compared to SCT women (28.7±7.1 years; p=0.018). The following maternal complications were more common among women with SCD in comparison to SCT: urinary tract infection (25.5 versus 8.9%; p=0.04), pneumonia (23.5 versus 1.8%; p=0.002), pulmonary hypertension (15.7 versus 0%; p=0.002), and blood transfusion during delivery or postpartum (33.3 versus 5.4%; p=0.001). Adverse perinatal outcome was more frequent in the SCD group compared to the SCT group: prematurity (49 versus 25%, p=0.01); mean gestational age at delivery (35.2 versus 37.9 weeks, p<0.001); fetal distress (56.9 versus 28.6%, p=0.006); birth weight <2,500 g (62.7 versus 17.9%, p<0.001); mean birth weight (2,183 versus 2,923 g, p<0.001), and small for gestational age infants (29.4 versus 10.7%, p=0.029). Two maternal deaths (3.9%) occurred in the group with SCD. Pregnant women with SCD are at greater risk for maternal morbidity and for adverse perinatal outcomes than women with SCT.

Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise

This study compared the hemorheological responses of a group of sickle cell trait (SCT) carriers with those of a control (Cont) group in response to 40 min of submaximal exercise (exercise intensity, 55% aerobic peak power) performed in two conditions: one with water offered ad libitum, i.e., the hydration (Hyd) condition, and one without water, i.e., the dehydration (Dehyd) condition. Blood and plasma viscosities, as well as red blood cell rigidity, were determined at rest, at the end of exercise, and at 2 h recovery with a cone plate viscometer at high shear rate and 37 degrees C. The SCT and Cont groups lost 1 +/- 0.7 and 1.6 +/- 0.6 kg of body weight, respectively, in the Dehyd condition, indicating a significant effect of water deprivation compared with the Hyd condition, in which body weight remained unchanged. Plasma viscosity increased with exercise and returned to baseline during recovery independently of the group and condition. As previously demonstrated, resting blood viscosity was greater in the SCT carriers than in the Cont group. Blood viscosity increased by the end of exercise and returned to baseline at 2 h recovery in the Cont group in both conditions. The blood viscosity of SCT carriers did not change in response to exercise in the Dehyd condition and remained elevated at 2 h recovery. This extended hyperviscosity, in association with other biological changes induced by exercise, could be considered as a risk factor for exercise-related events in SCT carriers, similar to vasoocclusive crises, notably during the recovery. In contrast, the Hyd condition normalized the hyperviscosity and red blood cell rigidity of the SCT carriers, with blood viscosity values reaching the same lower values as those found in the Cont group during the recovery. Adequate hydration of SCT carriers should be strongly promoted to reduce the clinical risk associated with potential hyperviscosity complications.