Mortality In Sickle Cell Disease Patients Research Articles

Multi-center study on mortality in children, and adults with sickle cell anemia-risk factors and causes of death

Sickle cell disease (SCD) is a major public health burden worldwide with increasing morbidity and mortality. The study evaluates the risk factors associated with mortality in SCD patients, between the years 2006 and 2020 at three hospitals in Oman. The analysis includes clinical manifestations, haematological, biochemical, and radiological parameters, use of antibiotics, and blood and exchange transfusions. Our cohort included 123 patients (82 males, 41 females), with a median age of 27 (Interquartile Range 21–35 years). SCD related complications included acute chest syndrome (ACS) in 52.8%, splenic sequestration in 21.1%, right upper quadrant syndrome in 19.5%, more than > 6 VOC/year in 17.9%, and stroke in 13.8%. At the terminal admission, patients had cough, reduced O2 saturation, crepitation and fever in 24.4%, 49.6%, 53.6% and 68.3% respectively. Abnormal chest X-ray and chest CT scan were seen in 57.7%, and 76.4% respectively. Laboratory parameters showed a significant drop in hemoglobin (Hb) and platelet counts from baseline, with a significant rise in WBC, LDH and CRP from baseline (p < 0.05, Wilcoxon Signed Ranks test). All patients received antibiotics, whereas, 95.9% and 93.5% received simple blood transfusions, and exchange transfusions respectively, and 66.6% required non-invasive ventilation. Among the causes of death, ACS is seen in 32 (26%), sepsis in 49 (40%), and miscellaneous in 42 (34%). Sudden death was seen in 32 (26%) of patients. Male gender, with low HbF, rapid drop in Hb and platelet, and increased in WBC, LDH, ferritin, and CRP, correlated significantly with mortality in this cohort.

Prevalence and Risk Factors of Stroke Among Children With Sickle Cell Disease: A Retrospective Study at a Tertiary Care Center.

Background Sickle cell disease (SCD) is a common autosomal recessive inherited hemoglobin disorder in many countries. Neurological complications are among the most disabling complications in SCD. Stroke and cerebral vasculopathy can lead to further neurological insult. Ischemic insults, stroke, and silent infarcts are preventable causes of morbidity and mortality in SCD patients. Understanding the epidemiology and characteristics of such patients will help to prevent complications. Methodology This is aretrospective studyconducted in a tertiary care center in Saudi Arabia. Cases of SCD admitted to the pediatric ward between the years 2019to 2023were included in the study.Demographic data, clinical diagnosis, and frequency of prior admissions were collected. Brain imaging results were reviewed and included. Furthermore, the study assessed common risk factors leading todeveloping astroke in SCD pediatric patients. Risk factors and clinical outcomes after stroke were also included. Results Eighty-one patients were enrolled. The mean age of stroke patients was 8.21±3.50 years while the mean age of non-stroke patients was 6.24±3.76 years. More than half of the patients were females in both the stroke (61.50%) and non-stroke groups (52.90%). ThirteenSCDpatients (16%) were diagnosed with stroke. Previous history of stroke, high mean corpuscular volume (MCV), and low red blood cells count (RBC) were statistically significant risk factors for stroke (p<0.0001), (p<0.0001), (p<0.03),respectively. Conclusion Stroke is one of the most devastating complications of SCD. The prevalence of stroke among SCD patients in our study was 16%. Transcranial Doppler ultrasound screening is the most important predictor of stroke.

Clinical outcomes following bone marrow transplantation in patients with sickle cell disease: A cohort study of US Medicaid enrollees.

Bone marrow transplantation (BMT) is currently the only curative therapy available for patients with sickle cell disease (SCD), but clinical outcomes in routine care are not well understood. We describe the rates of vaso-occlusive crises (VOCs), transplant complications, and mortality in SCD patients after BMT. A cohort study of SCD patients who underwent BMT was designed using US Medicaid claims data (2000-2013). A total of 204 SCD patients undergoing BMT were identified with a mean (SD) age of 10.6 (7.3) years, with 52.9% male and 67.6% African American. The overall VOC rate was 0.99 per person-year (95% CI: 0.91-1.07) over a median follow-up time of 2.1years (IQR: 0.8-4.3years). A total of 138 (67.6%) remained free of VOCs. The mortality rate was 1.7 (95% CI: 0.9-3.1) per 100 person-years, transplant-related complications occurred among 113 (55.4%) patients with an incidence rate of 38.2 (95% CI: 31.7-45.9) per 100 person-years, while 47 (23%) patients had GvHD with an incidence rate of 8.0 (95% CI: 6.0-10.7) per 100 person-years. Two thirds of the BMT recipients remained VOC-free over 2years of follow-up, but transplant-related complications, including GvHD occurred with high frequency. This highlights a continuing unmet need for alternative curative interventions in SCD.

Increase in Fetal Hemoglobin Levels in Pediatric Patients with Sickle Cell Disease after Vitamin D Replacement

Background: High fetal hemoglobin (HbF) levels reduce mortality and morbidity in sickle cell disease (SCD). Results from a prior clinical trial to assess safety of high dose vitamin D and our unbiased genomic analyses identifying a vitamin D regulated protein as a HbF inducer suggests that vitamin D replacement may increase HbF levels in SCD patients. To test this hypothesis, we performed a single center retrospective chart review investigating the impact of vitamin D replacement on HbF levels in our pediatric SCD population. Methods: We reviewed electronic medical records of pediatric patients with SCD with one or more serum vitamin D level who used vitamin D replacement from January 2007 to March 2020. SCD patients on chronic blood transfusion were excluded. Our cohort contained 81 SCD patients (ages: 2.3-19.9 years; 40 males) 71 HbSS, 6 HbSC, 3 HbSβ0, and1 Hb S-δβ. Vitamin D deficiency was defined as vitamin D levels &amp;lt; 30 ng/ml. All subjects were on hydroxyurea, with stable MCV (mean 96 fL at baseline and 95.6 fL during the study period). The patients received a median vitamin D dose of 2002 IU/day for a median of 229 days with a median follow-up of 365 days after replacement. Statistical analyses: Vitamin D deficient and non-deficient SCD patients data was compared at baseline by t test (for continuous variables with normal distribution), Wilcoxon test (for continuous variables with non-normal distribution), chi2 test (for categorical variables), and Fisher exact test (for categorical variables with small sample size). Linear relationships between vitamin D levels and HbF, CBC, BMI, and age were assessed using scatter plots and correlation coefficients (r value). Non-normal variables were log transformed to achieve normal distribution. A linear mixed effect (MLE) models were run to analyze linear relationship of variables of time dependent variables, including variable number of clinic visits and variable follow-up time. All models had 'vitamin D level" as an exposure variable; hydroxyurea and folic acid use as covariates, and one of the following as an outcome variable: HbF, hemoglobin, MCV, MCHC, reticulocyte count, WBC count, and platelet count. We performed mediation analysis to determine if HbF or MCV were intermediate variables for the effect of vitamin D on reticulocyte count. All LME models and scatter plots were created separately for the period of vitamin D replacement and a one-year follow-up period after cessation of vitamin D replacement to capture any lag period in HbF induction and sustained effect of vitamin D replacement. Results: The LME model, adjusting for hydroxyurea and folic acid, indicated that HbF increased by 0.68 percentage points with every 10 ng/ml rise in vitamin D levels during the vitamin D replacement period (p=0.04) and continued to rise after replacement, exhibiting a 2.2 percentage point rise per 10 ng/mL increase above replacement HbF levels during a 12 month follow-up period (p=0.005) (Figure 1, Table 1). WBC and absolute reticulocyte count (ARC) decreased significantly following vitamin D replacement according to the LME models (p&amp;lt;0.05) (Table 1). Reduction in ARC was due to HbF induction as per the mediation analysis. Conclusion: SCD patients have a 56.4-96.4 % prevalence of vitamin D deficiency reported in the literature. Several studies have shown that vitamin D deficiency is associated with increased morbidity and mortality in SCD patients. However, vitamin D screening and replacement are not routinely implemented in clinical practice. Our study is the first to analyze the effect of vitamin D replacement on HbF levels as a primary objective using longitudinal panel data. Our findings strongly suggest that vitamin D replacement can increase HbF levels and reduce laboratory markers such as ARC and WBC, whose elevation is associated with clinical severity. Disclosures Sheehan: Emmaus: Research Funding; Novartis: Research Funding; Global Blood Therapeutics: Research Funding.

Low morbidity and mortality with COVID-19 in sickle cell disease: A single center experience.

Coronavirus disease 2019 (COVID‐19) is caused by SARS‐CoV‐2 infection, which evolved into a global pandemic within a short time. Individuals with sickle cell disease (SCD) suffer from underlying cardiopulmonary comorbidities and are at risk of severe complications such as pneumonia, acute chest syndrome, thrombosis, stroke, and multiorgan failure. Whether COVID‐19 poses a high risk of morbidity and mortality in SCD patients remains unclear. Patients with SCD and COVID‐19 can present with overlapping clinical features such as respiratory symptoms with ground‐glass infiltrates, hyperinflammatory state, and increased risk of thromboembolism. This highlights the need to maintain a low threshold for testing for COVID‐19 infection among symptomatic and hospitalized SCD patients. We report a case series of nine hospitalized SCD patients diagnosed with COVID‐19 from March 18, 2020 to April 30, 2020 at a tertiary medical center in New York City. The mean age of the study population was 27.9 years, and interval since onset of symptoms and hospital presentation was 1–2 weeks. All patients in our series improved and were discharged home. This limited study shows that SCD patients, who are perceived to be high risk, maybe somehow protected from severe symptoms and complications of COVID‐19 infection.

Impact of sickle cell disease on presentation and progression of paediatric HIV: a retrospective cohort study.

HIV and sickle cell disease (SCD) are significant causes of morbidity and mortality in sub-Saharan Africa. Given their separate roles in immune dysregulation, our objective was to characterise the impact that SCD has on the presentation and progression of paediatric HIV. The study was a retrospective cohort study (study period 2004-2018). Cases of HIV+and SCD-afflicted patients (HIV+/SCD+) were obtained via electronic chart review from a paediatric HIV clinic in Kampala, Uganda and matched 1:3 with HIV+controls without SCD (HIV+/SCD-). Thirty-five HIV+/SCD+subjects and 95 HIV+/SCD- controls were analysed (39% female (51/130), age 3.6years (SD3.9)). At baseline, WHO clinical stage (64% total cohort Stage III/IV) and nutritional status (9.4% severe acute malnutrition) were similar for both groups, whereas HIV+/SCD+had higher though non-significant baseline CD4 count (1036 (SD713) vs 849 (SD638) cells/microlitre, P=0.20, two-tailed t-test). There were 19 deaths, 6 (17%) HIV+/SCD+and 13 (14%) HIV+/SCD-, with unadjusted/adjusted models showing no significant difference. Nutritional progression and clinical stage progression showed no significant differences between groups. Kaplan-Meier analysis showed a slower rate of treatment failures in the HIV+/SCD+cohort (P=0.11, log-rank survival test). Trajectory analysis showed that in the time period analysed, the HIV+/SCD+cohort showed a more rapid rise and higher total CD4 count (P=0.012, regression analysis). The study suggests that SCD does not adversely affect the progression of HIV in patients on ART. Further, HIV+/SCD+achieved higher CD4 counts and fewer HIV treatment failures, suggesting physiological effects due to SCD might mitigate HIV progression.

A Nationwide Analysis of Trends in in-Hospital Mortality in Patients with Sickle Cell Disease from 2000 to 2014

Background:Patients with Sickle cell disease (SCD) have high rates of hospitalizations in the US annually and carry a higher rate of in-hospital mortality compared to the general population. There have been very few therapeutic innovations for the treatment of SCD in the past few decades. Changes in mortality in these patients reflect the availability of healthcare delivery and improvements in management of long term complications of SCD. A nationwide analysis was conducted to study the mortality of patients in SCD over a period of 15 years (2000 to 2014). The national inpatient sample is a database supported by the Agency of Healthcare Research and Quality.Methods:In this study, all patients who were hospitalized between the years 2000 to 2015 were analyzed and mortality was studied in SCD patients. Mortality during hospital stay was studied with respect to hospital size, rural vs. urban location and the most common medical comorbidities. Data pertaining to demographic factors of gender, geographic location and hospital size (measure of expertise and facilities available) were extracted. Access to healthcare was assessed using insurance coverage as a surrogate and its effect on mortality was evaluated. The effect of common medical comorbid conditions such as atrial fibrillation (Afib), hypertension (HTN), hyperlipidemia (HLP), diabetes mellitus (DM), chronic kidney disease (CKD) and tobacco smoking was assessed. Chi-square test analysis was used to validate the statistical significance of difference seen between the groups with a significance identified with a p value< 0.05. Multivariate analysis was used to determine independent predictors of mortality.Results:Out of a total of 1280693 hospitalizations over 15 years there were 9230 deaths of which 4230 were males and 5000 were females. There was no difference in the rate of mortality between hospitals of different sizes (small vs. medium vs. large) teaching and non-teaching hospitals. The mortality/hospitalization ratio was statistically different between Northeast, Midwest, South and West regions (0.63%, 0.65%, 0.76% and 0.89 respectively; p = 0.008). A statistically significant difference was noted between the insurance status (Medicaid vs. Medicare vs. private vs. self) amongst sickle cell patients who died during hospitalization. The odds of dying during hospitalization has gradually decreased from 2000 to 2014 (p = 0.007). The average age of death was 43.8 years and the age group of 35-49 years accounted for the highest amount of mortality (33%). Univariate analysis showed a significant difference in the common medical comorbidities of HTN, HLP, DM, CKD and smoking status in SCD patients who died during hospitalization. Multiple regression analysis revealed females are less likely to suffer from in-hospital mortality than males (OR 0.80; P < 0.04), medical comorbidities of Afib, DM, HTN and CKD are significant risk factors (ORS: 4.3, 1.4, 1.8 and 1.3).Conclusions:In-hospital mortality in SCD patients has improved significantly over the past 2 decades which may reflect some improvements in health care delivery and possibly the usage of hydroxyurea. However, common medical comorbidities such as Afib, HTN, DM and CKD continue to remain significant risk factors for mortality in these patients. Aggressive management of these medical comorbidities may further decrease morbidity and mortality in SCD patients in the future. DisclosuresNo relevant conflicts of interest to declare.

Predictors of Adverse Outcome in Sickle Cell Disease Patients from Oman

Introduction: Sickle cell disease (SCD) is a major public health problem in Oman with high morbidity and mortality. The ability to identify the risk factors that are associated with mortality among SCD patients would permit accurate prognostication and provide an opportunity to use effective prophylactic management.Objective: The study aimed at identifying the risk factors associated with mortality in SCD patients by studying the clinical course of 86 patients who died at two tertiary care hospitals in Oman.Methods: We analyzed the electronic records of 86 SCD patients who died between 2006 to 2016. These data included cardiac parameters, SCD manifestations like frequency of painful crisis, acute chest syndrome, splenic and hepatic sequestration, dactylitis, and stroke. Furthermore, we also analyzed the haematological, biochemical and radiological parameters as well as use of antibiotics and exchange blood transfusion. Data were transcribed to Excel and later analyzed by IBM SPSS Ver23.Results±13.7. Previous complications prior to death included acute chest syndrome in 66.3% cases, followed by stroke in 20.9%, hepatic sequestration in 6.9%, splenic sequestration in 3.5% and dactylitis in 2.3% cases. At the terminal event, patients presented with fever, cough and crepitation in 47%, 29% and 36% respectively, while abnormal pulse, blood pressure, respiratory rate and O2 saturation were seen in 55%, 64%, 46% and 55% respectively. Further abnormal chest x-ray, CT scan and abdominal ultrasound were seen in 57.5%, 88.5% and 50% respectively. Amongst the haematology parameters, there was a significant drop in the mean hemoglobin and platelet counts from baseline, whereas there was a significant rise in the WBC counts (p<0.05, student's t test). The biochemical parameters showed a significant rise in the LDH and CRP levels (p<0.05). All patients received antibiotics, 88% received blood transfusions, 35.7% received exchange transfusions, whereas 87.5% required NIV/ventilation. Finally, all patients presented with multi-organ terminal events that varied in the severity, but sepsis showed the commonest cause of death (54.3%).Conclusion: Multi-organ failure was mostly associated with the terminal events relating to mortality. Although sepsis played a major role as a cause of death in association with multiorgan failure, low hemoglobin, and low platelet counts with increased WBC counts along with elevated LDH and CRP played a significant role in the terminal event in this cohort of SCD patients. DisclosuresNo relevant conflicts of interest to declare.

Optical laser trapping for studying the deformability of sickle red blood cells in response to hydroxyurea

Background: Sickle cell disease (SCD) is prevalent in Basrah city and affects the red blood cell (RBC) deformability and thereby causes disease symptoms. Hydroxyurea (HU) is effective in reducing morbidity and mortality in SCD patients by different mechanisms. Objectives: The aim of the study was to investigate the effect of HU on RBC deformability among SCD patients by direct laser optical trapping (OT) technique. Materials and Methods: Blood samples from SCD patients and control groups were prepared in the medical laboratory of Basrah Center for Hereditary Blood Diseases and transferred into physics laboratory wherein the laser system was presented and built-in. RBCs from each sample were exposed to three different powers of laser 5, 15, and 20 mW for 15 s and then were released and followed for 2 min. The images for each trapped RBC were obtained and at relaxation sequential times. The percentage changes in the diameters of trapped RBCs were measured for control and patient groups. Results: SCD patients were divided into two groups depending on whether they were receiving HU (39 patients) or not (43 patients). They were matched with 50 healthy individuals (control) regarding age and gender. We found that all the trapped RBCs were affected during the trapping time and then returned toward near normal with some differences between the groups and according to the power used. The deformability of HU group was better and closure to the control. Conclusion: The presented laser system and OT technique with optimal power are effective to study the RBC characteristics and deformability. HU is effective in improving RBC deformability among SCD patients.

Vascular Permeability Drives Susceptibility to Influenza Infection in a Murine Model of Sickle Cell Disease

Sickle cell disease (SCD) is a major global health concern. Patients with SCD experience disproportionately greater morbidity and mortality in response to influenza infection than do others. Viral infection is one contributing factor for the development of Acute Chest Syndrome (ACS), a major cause of morbidity and mortality in SCD patients. We determined whether the heightened sensitivity to influenza infection could be reproduced in the two different SCD murine models to ascertain the underlying mechanisms of increased disease severity. In agreement with clinical observations, we found that both genetic and bone marrow-transplanted SCD mice had greater mortality in response to influenza infection than did wild-type animals. Despite similar initial viral titers and inflammatory responses between wild-type and SCD animals during infection, SCD mice continued to deteriorate and failed to resolve the infection, resulting in increased mortality. Histopathology of the lung tissues revealed extensive pulmonary edema and vascular damage following infection, a finding confirmed by heightened vascular permeability following virus challenge. These findings implicate the development of exacerbated pulmonary permeability following influenza challenge as the primary factor underlying heightened mortality. These studies highlight the need to focus on prevention and control strategies against influenza infection in the SCD population.

The factors influencing utilization of hospital services by adult sickle cell disease patients: a systematic review protocol

The factors influencing utilization of hospital services by adult sickle cell disease patients: a systematic review protocol

135 Cardiovascular Complications in Sickle Cell Disease

<h3>Introduction</h3> Sickle cell disease (SCD) is a genetic disorder affecting the production of haemoglobin (Hb). It has life-long consequences with multi-organ involvement including the cardiopulmonary circulation and an increased mortality. Although all SCD patients share the same genetic defect, the phenotype varies. This suggests other factors, unrelated to the Hb mutation, play an important role particularly in later decades. This retrospective study examined patient survival attending a specialist tertiary centre in the United Kingdom based on Tricuspid Regurgitant Jet Velocity (TRJ) measured by echocardiography and associated laboratory studies. <h3>Method</h3> A retrospective analysis of TRJ and diastolic function (lateral E/E’ ratio) assessed by echocardiography in 127 intensively treated steady-state SCD patients (mean age 40 +/- 12 years) screened for cardiovascular complications. Laboratory studies were also analysed. <h3>Results</h3> The clinical characteristics of patients in this study is summarised in Table 1. 15% of patients had a TRJ between 2.6–2.99 m/s and 9% with TRJ &gt;3.0 m/s. 11% of patients had diastolic dysfunction using lateral E/E’ ratio. When compared to patients with a TRJ &lt;2.5 m/s, the risk of death is 4 times higher in the 2.6–2.99 TRJ group and 24 times higher in the &gt; 3.0 TRJ group. See Figure 1. Lateral E/E’ ratio (beta = 0.88, p = 0.015), left atrial area (beta = 0.38, p &lt; 0.001) and microalbuminuria (beta = 0.10, p = 0.05) were independently associated with TRJ. <h3>Conclusion</h3> Mortality in SCD patients with raised TRJ remains high despite intensive therapy, such as exchange transfusion, directed at correcting Hb. Screening with echocardiography remains an important tool in identifying high-risk patients. Additional therapies directed at the premature ageing of the cardiopulmonary circulation are urgently needed.

Sickle Cell Disease Mortality in California and Georgia 2004-2008

▪On-going public health surveillance efforts in sickle cell disease (SCD) are critical for understanding the course and outcomes of this disease over time. Once nearly universally fatal by adolescence, many patients are living well into adulthood and sometimes into retirement years. Previous SCD mortality estimates have relied on data from death certificates alone or from deaths of patients receiving care in high volume hematology clinics, resulting in gaps in reporting and potentially biased conclusions.The Registry and Surveillance System for Hemoglobinopathies (RuSH) project collected and linked population-based surveillance data on SCD in California and Georgia from a variety of sources for years 2004-2008. These data sources included administrative records, newborn screening reports and health insurance claims as well as case reports of adult and pediatric patients receiving care in the following large specialty treatment centers: Georgia Comprehensive Sickle Cell Center, Georgia Regents University, Georgia Comprehensive Sickle Cell Center at Grady Health Systems and Children’s Healthcare of Atlanta in Georgia, and Children’s Hospital Los Angeles and UCSF Benioff Children’s Hospital Oakland in California. Cases identified from these combined data sources were linked to death certificates in CA and GA for the same years.Among 12,143 identified SCD cases, 640 were linked to death certificates. Combined SCD mortality rates by age group at time of death are compared to combined mortality rates for all African Americans living in CA and GA. (Figure 1). SCD death rates among children up to age 14 and among adults 65 and older were very similar to those of the overall African American population. In contrast, death rates from young adulthood to midlife were substantially higher in the SCD population.Overall, only 55% of death certificates linked to the SCD cases had SCD listed in any of the cause of death fields. Thirty-four percent (CA) and 37% (GA) had SCD as the underlying cause of death. An additional 22% and 20% (CA and GA, respectively) had underlying causes of death that were not unexpected for SCD patients, including related infections such as septicemia, pulmonary/cardiac causes of death, renal failure and stroke. The remaining 44% (CA) and 43% (GA) had underlying causes of death that were either not related to SCD (e.g., malignancies, trauma) or too vague to be associated with SCD (e.g., generalized pulmonary or cardiac causes of death. Figure 2 shows the number of deaths by state, age group at death and whether the underlying cause of death was SCD specific, potentially related to SCD or not clearly related to SCD. While the number of deaths was too small to use for life expectancy calculations, there were more deaths over age 40 than under age 40 during this five year period.This effort represents a novel, population-based approach to examine mortality in SCD patients. These data suggest that the use of death certificates alone to identify deceased cases may not capture all-cause mortality among all SCD patients. Additional years of surveillance are needed to provide better estimates of current life expectancy and the ability to track and monitor changes in mortality over time. On-going surveillance of the SCD population is required to monitor changes in mortality and other outcomes in response to changes in treatments, standards of care and healthcare policy and inform advocacy efforts.This work was supported by the US Centers for Disease Control and Prevention and the National Heart, Lung and Blood Institute, cooperative agreement numbers U50DD000568 and U50DD001008. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Renal Disease in Sickle Cell: Clinically Varied and Associated with Increased Mortality

AbstractAbstract 90▪▪This icon denotes a clinically relevant abstractThe Walk-Phasst Study of sickle cell disease (SCD) affords a unique opportunity to examine renal function in a large number of adults with SCD. Extensive clinical and laboratory data were obtained on 463 adults with HbSS and 127 adults with HbSC. Where possible, correlates for estimated glomerular filtration rate (eGFR, calculated by the 4-value MDRD equation) and albuminuria/proteinuria were also evaluated in historical data, from SS adults in the CSCCD cohort and the Multicenter Study of Hydroxyurea (MSH) in sickle cell disease.Adjusted decline in eGFR was more rapid in SS compared with SC, at −2.6 and −0.92 ml/min/1.73 m2/year, respectively (p<0.001). In SS, similar declines in cross-sectional eGFR with age were seen in adults in the CSCCD (n=705) and MSH (n=298) cohorts, at −2.9 and −1.9 ml/min/year (BSA corrected), respectively. Multivariate analysis of the SS cohort in of Walk-Phasst revealed that depressed eGFR values were associated with an elevated estimated pulmonary arterial systolic pressure (as reflected in a higher tricuspid regurgitant jet velocity, measured by echocardiogram, p=0.007) and with evidence for inflammation (an elevated white blood cell count, p=0.018). In SC adults, in contrast, lower eGFRs were primarily associated with a diminished erythroid reserve (depressed absolute reticulocyte counts, P=0.005).Albuminuria (≥30 mg albumin/gm creatinine) was detectable in 66 and 41 % of adults with HbSS and HbSC in Walk-Phasst (185/287 evaluable SS and 25/61 evaluable SC, p=0.001). In Walk-Phasst, albuminuria in SS was associated with evidence of increased red cell destruction (lower total hemoglobin (P=0.07), higher LDH (P<0.001), and higher reticulocyte count (P=0.017)). In SC, albuminuria was associated with a higher LDH (P=0.01). 159/657 (24%) of adult SS subjects in the CSCCD cohort had trace to 4+ proteinuria, using a method (urine dipstick analysis) that is less sensitive and less quantitative than the albumin-to-creatinine ratio used in Walk-Phasst. Multivariate analyses again suggested a strong association between a depressed Hgb and proteinuria (P<0.001) in CSCCD, and LDH was also associated with proteinuria, in univariate analyses (P<0.001). In Walk-Phasst the absence of albuminuria in all subjects with SCD was associated with lesser mortality in multivariate analyses (Hazard ratio 0.62 (0.4–0.9, P=0.02). No similar association was seen between eGFR and mortality.Subjects with SS in Walk-Phasst had depressed serum bicarbonate levels, of 23.8±3.4 compared with 24.7±3.2mEq/dL in SC (p<0.005) and 24.8±3.3 mEq/dL in the non-CKD general population (Shah et al, 2009). In multivariate analyses, acidemia was associated with both increased destruction and decreased production of red cells, e.g. higher EPO (P=0.003) and total bilirubin levels (P<0.001), but lower reticulocyte counts (P=0.06). Impaired physiologic functioning in acidemic subjects with HbSS, manifest as a depressed 6MWD (P<0.001) and a lower eGFR (P<0.001), was seen. No effect of bicarbonate level on mortality in SCD patients was evident in Walk-Phasst.In conclusion, renal function is perturbed in sickle cell syndromes in several ways, including more rapid decrement in eGFR, highly prevalent albuminuria, and, in SS, marked abnormalities in acid-base balance. Albuminuria is associated with anemia in two large cohorts of sickle cell disease patients and, in Walk-Phasst, with evidence for enhanced red cell destruction. Importantly, albuminuria correlated with an increased risk for mortality in sickle cell disease.(We acknowledge the many contributions made by the Walk-PHASST Investigators: Badesch DB, Barst RJ, Castro OL, Girgis RE, Gibbs JS, Goldsmith JC, Hannoush H, Hassell KL, Kato GJ, Krishnamurti L, Lanzkron S, Machado RF, Morris CR, Novelli EM, Rosenzweig EB, Sachdev V, Schraufnagel DE, Taylor JG 6th.) Disclosures:No relevant conflicts of interest to declare.

Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis

Mixed haematopoietic chimerism for sickle cell disease prevents intravascular haemolysis

Therapeutic challenges in childhood sickle cell disease. Part 1: current and future treatment options.

Therapeutic challenges in childhood sickle cell disease. Part 1: current and future treatment options.