Closing Knowledge Gaps Among Parents of Children with Sickle Cell Trait

Abstract Background Nearly 8% of African Americans carry sickle cell trait (SCT) and approximately 2000 infants in the United States are born with sickle cell disease (SCD) annually. SCT knowledge is necessary for individuals with SCT to make informed reproductive decisions since they are at risk of having children with SCD. Despite state programs that inform parents of their child's SCT status via telephone call, >80% of adults with SCT do not know their status. This may be because many parents have low health literacy (HL), low baseline SCT knowledge, and/or may not achieve high sustained SCT knowledge after non-standardized phone encounters. The SCTaware education program was designed to improve SCT education to close knowledge gaps that may exist after telephone-only education. It also aims to increase parents' SCT status awareness and their ability to inform their affected children in the future. Objectives The objectives of this interim analysis were to assess central Ohio parents' SCT knowledge after being educated about their child's SCT status by telephone (standard of care) and to explore if SCTaware improves parents' knowledge immediately and one month after receiving it. Methods A multidisciplinary team (hematologists, a genetic counselor, HL experts, SCT educators, parent stakeholders, and visual design experts) developed SCTaware, a videoconference-administered education program that is delivered by a trained educator and includes SCT knowledge objectives, HL-informed communication strategies (e.g., teach-back), visuals scoring highly for understandability, and access to narrated post-education review materials. Through electronic medical record review, we identified English-speaking biological parents of infants with SCT who were informed of their child's SCT by telephone. Adult parents who were able to be contacted by telephone were invited to participate if they did not have SCD or a child with SCD, had not received SCT education in central Ohio for another child, were not (or partner was not) currently pregnant, and had access to an electronic device capable of videoconferencing. After informed consent, parents reported their and their child's SCT status, completed a demographic survey, a HL assessment, and the published Sickle Cell Trait Knowledge Assessment (SCTKA) consisting of eight questions. Participants then received SCTaware and repeated the SCTKA and report of their and their child's SCT status immediately and one month later. SCTKA scores <75% correct were considered low. Data were summarized descriptively. Linear mixed effects models with random intercept for each parent were used to assess scores longitudinally. Results Of the 297 children with SCT whose parent received telephone education between March 2020-April 2021, 114 had a parent who was able to be contacted, 22 were ineligible when contacted, and five declined participation because they reported having adequate knowledge. To date, 63 parents have enrolled, 54 have completed baseline surveys (Table 1), 44 have completed SCTaware, and 35 have completed the one-month follow-up. Following telephone education, 44% of participants had high SCT knowledge. Participants' mean SCTKA scores post-telephone education did not significantly differ whether they had received telephone education ≤3 months or >3 months before enrolling in the study (64% correct vs. 71% correct, p=0.30). Of those who had completed SCTaware, 42 (95%) achieved high SCT knowledge immediately after. Of those who have completed the one-month follow-up, 94% continue to have high knowledge. Participants with low HL had significantly lower SCTKA scores post-telephone education but those with high and low HL achieved and maintained high sustained knowledge one month after receiving SCTaware (Figure 1). Discussion Our interim analysis shows that over half of parents, especially those with low HL, have low SCT knowledge after receiving education by telephone regarding their infant's diagnosis of SCT. SCTaware is a scalable tool that could be widely implemented as an initial program or as a follow-up to telephone education if final analyses confirm that SCTaware leads to sustained knowledge gains. Future studies, however, need to determine parent access to and satisfaction with SCTaware and if individuals use the knowledge gained to inform their reproductive decision-making and to inform their affected children. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Sickle Cell Trait Knowledge and Health Literacy in Caregivers Who Receive in-Person Sickle Cell Trait Education

Blood ◽

10.1182/blood.v128.22.2340.2340 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2340-2340 ◽

Cited By ~ 1

Author(s):

Susan E Creary ◽

Ismahan Adan ◽

Joseph R Stanek ◽

Sarah O'Brien ◽

Deena J Chisolm ◽

...

Keyword(s):

Health Literacy ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Sickle Cell Trait ◽

Primary Care Providers ◽

The United States ◽

Care Providers ◽

Childbearing Age ◽

Limited Health Literacy ◽

Limited Health

Abstract Background Sickle cell trait (SCT) affects approximately 8% of African Americans and these individuals are at risk of having children with SCT and sickle cell disease (SCD). Universal newborn screening in the United States detects SCT, but only 16% of individuals of childbearing age with SCT know their status. This is because SCT is not reliably recorded in medical records and SCT may not be consistently or effectively communicated to caregivers. Interventions that increase caregivers' SCT knowledge are important so that individuals with SCT can make informed decisions about their reproductive health. Objectives The objectives of this study were to determine if in-person SCT education with a trained educator improved caregivers' SCT knowledge and to assess caregivers' satisfaction with their SCT education. Methods Nationwide Children's Hospital (NCH) is a SCT referral center in Columbus, OH. At NCH, it is standard that caregivers of infants with SCT who are referred by their primary care providers receive in-person SCT education using visual aids from an educator who has completed a hemoglobinopathy counselor training course. From August 2015-July 2016, we performed a prospective, cross-sectional study of English-speaking caregivers of infants with hemoglobin S-trait who presented for education. Caregivers were excluded if they had SCD or previously received SCT education at NCH. Prior to receiving education, subjects electronically reported their demographic information and completed a health literacy assessment using the Newest Vital Sign (NVS, range 0-6) and an 8-question (true/false, multiple choice) pilot-tested, SCT knowledge assessment (SCTKA) that included items from a published SCT knowledge study and items routinely discussed during NCH SCT education. Lower NVS scores suggest a higher likelihood of limited health literacy. Caregivers with SCTKA scores <75% were considered to have low knowledge. Immediately after receiving education, caregivers repeated the SCTKA and provided feedback about the session. Assessments were not available to the educator during the session. The Wilcoxon Signed-Rank test was used to compare SCTKA scores pre- and post-education. Mann-Whitney tests were used to compare NVS and pre-SCTKA scores between those with high and low SCT knowledge after education. Results We recruited 114/374 eligible caregivers who presented during the study period and 113 completed the study. Subjects were mostly female (77%), 18-39 years of age (95.6%), parents or step parents (95.6%) of the child, and some (34.8%) reported that they had SCT. Many caregivers (52.2%) had NVS scores <4, but most (94.7%) reported the education was easy to understand, their questions were answered (99.1%), and they do intend to inform their child of their SCT status (99.1%). Caregivers' median pre-education SCTKA score significantly improved from 62.5% (IQR=25%) to 87.5% (IQR=12.5%) with education (p <0.0001). Only 38.1% of caregivers had high SCT knowledge pre-education but most (90.3%) achieved high knowledge with education. Caregivers with low SCT knowledge after education had significantly lower NVS scores (median=1, p=0.0286) and baseline SCTKA scores (median=50%, p=0.0032) compared to those with high SCT knowledge after education (NVS=3.5, baseline SCTKA median=62.5%). Discussion Our study suggests that caregivers' baseline SCT knowledge is low and improves with in-person education. Despite overall caregiver satisfaction and intensive in-person education from a trained educator, approximately 10% did not achieve high SCT knowledge and our results show that these caregivers may have lower baseline SCT knowledge and health literacy. Assessing caregivers' health literacy and SCT knowledge prior to education may be useful to allow educators to modify their education to meet the needs of those with limited health literacy and SCT knowledge. Future studies need to determine if tailored education results in high SCT knowledge among all caregivers, if caregivers' SCT knowledge is sustained, and if high caregiver knowledge results in more individuals with SCT knowing their status and using this knowledge to inform their reproductive decision-making. Disclosures No relevant conflicts of interest to declare.

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Hydroxyurea to Treat Pediatric Sickle Cell Disease in Haiti - a Preliminary Report

Blood ◽

10.1182/blood.v128.22.1313.1313 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1313-1313

Author(s):

Nicholas McGregor ◽

Emmeline Lerebours ◽

Prasad Bodas

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Laboratory Data ◽

The United States ◽

Western Hemisphere ◽

Cell Disease ◽

Open Label ◽

Serious Adverse Events

Abstract Introduction. Haiti is the poorest nation in the Western Hemisphere, and the prevalence of sickle cell disease (SCD) in thatnation is twice that among African-Americans in the United States. Patients with SCD in Haiti have limited access to preventative care and disease management measures due to scarce healthcare resources. Hydroxyurea (HU) is a compelling option for the amelioration of complications of SCD in Haiti due to its relatively low cost, proven safety, and well-documented efficacy. Hydroxyurea programs have been implemented in India and in several African settings, however little data existto demonstrate the acceptability or feasibility of such an effort in Haiti. Study Design/Objectives. This is an open label, single arm pilot study with the primary objective of examining the acceptability and feasibility of the use of HU to treat children with SCD in an existing pediatric SCD program in Port-au-Prince, Haiti. Acceptability was defined as enrollment of a minimum of two-thirds of patients who are offered participation in the study. Feasibility was defined as two thirds of the enrolled patients being compliant with a defined minimum number of mandated study visits, lab draws, and HU doses. Secondary objectives include documenting the effect of HU on renal, hepatic, and bone marrow function as well as describing the incidence of clinical events in Haitian sickle cell patients taking HU. Methods. Patients with HbSS disease, age 2-15 years, who met minimum hematologic, renal, and hepatic parameters, were eligible for the study. Patients were approached for inclusion into the study consecutively during three separate enrollment periods from November 2015 through June 2016. The starting dose of Hydroxyurea (capsule and suspension form were available) was 20mg/kg which was increased to a maximum dose of 25mg/kg. Study visits occurred every 4 to 8 weeks at which point laboratory and clinical efficacy parameters, as well as potential adverse effects history were collected and dose modifications occurred. The study period for each patient will last 1 year. Akron Children's Hospital (ACH) IRB and the Haitian National Ethics Board approved the study. Funding for this project is provided through grants from the American Academy of Pediatrics and the ACH Foundation. Results. The study is ongoing with the enrollment period being closed as of June 2016. Forty-three patients have been enrolled, with a mean length of participation of 17.6 weeks (range 0-32 weeks).Forty-seven patients were offered participation in the study and 45 signed consent and underwent the screening process, generating an acceptability measure of 95.7%. Two out of the 45 screened patients were excluded based on results from screening labs (1 non-HbSS on confirmatory electrophoresis, 1 severe anemia) resulting in the final enrollment of 43 patients (23M:20F, mean age 9 years). Feasibility is being actively assessed.There have been no serious adverse events and no deaths. Three out of 43 enrolled patients were lost to follow-up and removed from the study due to missing 3 consecutive study visits (see figure 1). Compliance with mandated study visits was high among the enrolled patients with an attendance of 92.9% of the visits. Percent attainment of mandated laboratory tests is shown in table 1. No patients have had HU dose interruptions based on abnormal lab tests. Sixteen study patients have 6 month hematologic laboratory data available at this time: mean Hemoglobin and MCV have increased from 7.1 to 7.9g/dL and 90.6 to 107.1fL, respectively, and mean WBC and platelet count have decreased from 18.0 to 12.4(10^9/mL) and 557 to 413(10^9/mL), respectively. Conclusion. Results suggest that HU isan acceptable option for treating children with sickle cell disease in Haiti. Our preliminary data show that HU is feasible, safe, and effective in this setting. Challenges exist in ensuring reliable laboratory follow-up and will likely have to be addressed on an individual clinic and laboratory basis. Disclosures No relevant conflicts of interest to declare.

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Perspective From the National Medical Association

PEDIATRICS ◽

10.1542/peds.83.5.911 ◽

1989 ◽

Vol 83 (5) ◽

pp. 911-911

Author(s):

Roselyn Payne Epps

Keyword(s):

Sickle Cell Disease ◽

Medical Association ◽

Sickle Cell ◽

Education Program ◽

Well Being ◽

The United States ◽

Professional Organization ◽

Cell Disease ◽

National Medical

I am pleased to comment as a member of the National Medical Association, the professional organization founded in 1895, which currently represents the 14,000 black physicians practicing in the United States. Members of the National Medical Association (many of whom have been inspired by the leadership of Dr Roland B. Scott) have been and continue to be in the forefront of sickle cell disease research. Their sustained interest and that of many other colleagues has contributed to the research accomplishments we observe today. On the other hand, some physicians have been reluctant to assume a prominent role in sickle cell screening, counseling, and follow-up because of their own uncertainties and legitimate differences of opinion. During this conference, experienced and knowledgeable speakers have eloquently presented varying and sometimes divergent points of view, reflecting existing practices and highlighting the need for consensus development. As the consensus panel approaches its deliberations, I would like to emphasize that the health of the child and family must be paramount. I define health in its broad sense as the physical, mental, and social well-being of children and families. Results of the collaborative oral penicillin study, presented by Dr Gaston, leave no doubt that identification of sickle cell disease during infancy and prevention of its complications are imperative. Also, many speakers from successful programs spoke of the extensive time, effort, and resources required to screen, follow up, counsel, and treat patients and to coordinate services. I request that the panel carefully consider the advisability and feasibility of a public health education program, patterned after the highly successful high blood pressure education program launched by the National Heart, Lung, and Blood Institute, which included every resource of the country.

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

Ethnicity & Disease ◽

10.18865/ed.27.1.11 ◽

2017 ◽

Vol 27 (1) ◽

pp. 11 ◽

Cited By ~ 7

Author(s):

Nicole D. Dueker ◽

David Della-Morte ◽

Tatjana Rundek ◽

Ralph L. Sacco ◽

Susan H. Blanton

Keyword(s):

United States ◽

Chronic Kidney Disease ◽

African Americans ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Trait ◽

The United States ◽

Genetic Mutation ◽

Single Mutation ◽

Increased Risk

Sickle cell anemia (SCA) is a common hematological disorder among individuals of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and CKD was defined as eGFR < 60 mL/min/1.73 m2. Within our sample, there were 16 individuals with SCT (SCT carriers). We found that SCT carriers had a mean eGFR that was 12.12 mL/min/1.73m2 lower than non-carriers (P=.002). Additionally, SCT carriers had 2.72 times higher odds of CKD compared with non-carriers (P=.09). Taken together, these novel results show that Hispanics with SCT, as found among African Americans with SCT, may also be at increased risk for kidney disease.Ethn Dis. 2017; 27(1):11-14; doi:10.18865/ed.27.1.11.

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Malaria continues to select for sickle cell trait in Central Africa

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1505665112 ◽

2015 ◽

Vol 112 (22) ◽

pp. 7051-7054 ◽

Cited By ~ 45

Author(s):

Eric Elguero ◽

Lucrèce M. Délicat-Loembet ◽

Virginie Rougeron ◽

Céline Arnathau ◽

Benjamin Roche ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Trait ◽

Genetic Disorder ◽

Central Africa ◽

The United States ◽

Malaria Prevalence ◽

Current Data ◽

World Health ◽

Human Populations ◽

Health Organization

Sickle cell disease (SCD) is a genetic disorder that poses a serious health threat in tropical Africa, which the World Health Organization has declared a public health priority. Its persistence in human populations has been attributed to the resistance it provides to Plasmodium falciparum malaria in its heterozygous state, called sickle cell trait (SCT). Because of migration, SCT is becoming common outside tropical countries: It is now the most important genetic disorder in France, affecting one birth for every 2,400, and one of the most common in the United States. We assess the strength of the association between SCT and malaria, using current data for both SCT and malaria infections. A total of 3,959 blood samples from 195 villages distributed over the entire Republic of Gabon were analyzed. Hemoglobin variants were identified by using HPLCy (HPLC). Infections by three species of Plasmodium were detected by PCR followed by sequencing of a 201-bp fragment of cytochrome b. An increase of 10% in P. falciparum malaria prevalence is associated with an increase by 4.3% of SCT carriers. An increase of 10 y of age is associated with an increase by 5.5% of SCT carriers. Sex is not associated with SCT. These strong associations show that malaria remains a selective factor in current human populations, despite the progress of medicine and the actions undertaken to fight this disease. Our results provide evidence that evolution is still present in humans, although this is sometimes questioned by scientific, political, or religious personalities.

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Abstract P053: Diabetes Risk Prediction and Sickle Cell Trait in African Americans From CARDIA and the Jackson Heart Study

Circulation ◽

10.1161/circ.135.suppl_1.p053 ◽

2017 ◽

Vol 135 (suppl_1) ◽

Author(s):

Mary E Lacy ◽

Gregory A Wellenius ◽

Adolfo Correa ◽

Mercedes R Carnethon ◽

Robert I Leim ◽

...

Keyword(s):

African Americans ◽

Risk Prediction ◽

Sickle Cell ◽

Prediction Models ◽

Sickle Cell Trait ◽

Model Performance ◽

Jackson Heart Study ◽

Discriminative Ability ◽

Heart Study

Introduction: Existing models to predict incident diabetes mellitus (DM) perform better in Whites than African Americans. In models that incorporate hemoglobin A1c (A1C) as a predictor of DM, the difference in model performance by race is more pronounced. In a recent study, we found that A1C was systematically underestimating glycemia in African Americans with sickle cell trait (SCT). Hypothesis: Given the poorer performance of DM prediction models in African Americans than Whites and the impact of SCT on the A1C-glycemia association, we hypothesized that incorporating sickle cell trait into DM prediction models would improve the ability of the model to predict future risk of DM. Methods: We pooled data collected from 2000-2012 on 3,122 African Americans (8.6% with SCT) from the Jackson Heart Study (JHS; n=2,065; mean age=54.71 years) and CARDIA (n=1,057; mean age=44.53). Over 5 years of follow-up in CARDIA and 10 years of follow-up in JHS, 85 CARDIA participants (8.1%) and 342 JHS participants (16.6%) developed DM. Using generalized estimating equations to account for correlation of repeated measures, we compared the discriminative ability and net reclassification improvement (NRI) resulting from the addition of SCT for a series of prediction models. Results: Overall, the addition of SCT to prediction models did not result in significant improvement in the discriminative ability. However, by the NRI index, the addition of SCT to measures of glycemia and to a fuller risk prediction model did improve prediction of DM. In the full model, adding SCT*A1C as a predictor resulted in 2% of events being reclassified as higher risk and 45% of non-events being reclassified as lower risk. Conclusion: Our results suggest that incorporating SCT into DM prediction for African Americans may result in modest improvement in model performance.

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Cardiovascular Outcomes in African Americans with Sickle Cell Trait and Chronic Kidney Disease

American Journal of Nephrology ◽

10.1159/000496058 ◽

2019 ◽

Vol 49 (2) ◽

pp. 93-102 ◽

Cited By ~ 3

Author(s):

Kabir O. Olaniran ◽

Nwamaka D. Eneanya ◽

Andrew S. Allegretti ◽

Sophia H. Zhao ◽

Maureen M. Achebe ◽

...

Keyword(s):

Chronic Kidney Disease ◽

African American ◽

Cardiovascular Risk ◽

African Americans ◽

Kidney Disease ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Increased Risk ◽

The Mean

Background: Sickle cell trait (SCT) is common among African Americans and has been historically considered to be benign. Recently, SCT has been associated with an increased risk for chronic kidney disease (CKD) and cardiovascular disease in the general population. Our understanding of SCT has been extrapolated largely from data of patients with sickle cell disease (SCD). Notably, in SCD, the outcomes differ by sex. The effect of SCT on cardiovascular risk in the African American CKD population is unknown, and the interaction between SCT and sex on cardiovascular risk has not been investigated. Methods: We performed a 2-center retrospective cohort study of all African American patients with SCT using international classification of disease diagnosis codes and CKD (using the 2012 Kidney Disease Improving Global Outcomes criteria) with at least 1 year of follow-up between January 2005 and December 2017. A reference group of African American CKD patients without SCT was used as a comparator during the same period. SCT patients and the reference patients were matched at baseline for age, sex, comorbidities, and proteinuria. Primary outcomes were incident coronary artery disease (CAD), incident stroke, and all-cause mortality. Analysis of effect modification between sex and SCT on primary outcomes was performed. Results: We identified 621 African American CKD patients, 217 SCT patients, and 404 reference patients. The mean age was 56 ± 13 years and 66% were female. The mean estimated glomerular filtration rate was 69 ± 30 mL/min. The mean follow-up time was 8 ± 4 years. There were no significant differences in the primary outcomes comparing SCT patients to matched controls. The interaction term between SCT and sex, however, was significant in the CAD model (p < 0.01). Stratification by sex showed no increased risk in females but a significantly increased risk for CAD in male SCT patients (hazard ratio [HR] 2.14; 95% CI 1.18–3.86), which persisted after multivariable analysis (HR 2.13; 95% CI 1.17–3.86). Conclusion: SCT is associated with an increased risk for CAD in African American males with CKD. The excess risk in males with SCT appears to follow the same pattern as risk in males with SCD. Larger studies are needed to confirm these findings.

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Autoantibody Formation and Alloimunization in Sickle Cell Disease Patients.

Blood ◽

10.1182/blood.v104.11.4099.4099 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4099-4099

Author(s):

Marcia C.Z. Novaretti ◽

Eduardo Jens ◽

Thiago Pagliarini ◽

Andreia L. Rodrigues ◽

Pedro E. Dorlhiac-Llacer ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Study Group ◽

Cell Disease ◽

The One ◽

Design And Methods ◽

The Impact ◽

Transfusion History ◽

Autoantibody Formation

Abstract Background: Alloantibody and autoantibody formation to red blood cell (RBC) antigens is one of the observed complications in sickle cell disease patients (SCD). The incidence of alloimmunization and autoantibodies in this selected group of patients is particularly high, although the clinical implication of autoantibodies in sickle cell disease patients is not clear. The purpose of this study is to evaluate the rate of alloantibody and autoantibody formation in SCD patients. Study design and methods: A retrospective analysis of transfused sickle cell disease patients followed at Fundacao Pro-Sangue Hemocentro de Sao Paulo between 1988 and 2004 were retrieved. Data on transfusion history, were correlated with development of alloantibodies and autoantibodies. Results: The study group was composed by 43 sickle cell disease patients followed for a mean of 89 months (22–116). The number of RBC units transfused (mean) was 64 (4–208). The development of the first alloantibody was detected after a mean of 40 months (1–107) after the first transfusion in our institution. Out of these patients, 31 (72.1%) were identified with RBC alloantibodies; 9 of these patients (21%) had both allo and autoantibodies to RBC antigens, whereas 5 (55.6%) developed autoantibodies after alloimmunization. The one remainder had only autoantibodies. Conclusion: The alloimmunization rate was extremely high (72.1%) and can be partially explained because of the extended time of follow-up (mean of 89 months). Different from the literature the development of autoantibodies preceeded alloantibodies in 44.4%. The impact of this observation in clinical practice warrants further investigation.

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Hemoglobinuria Is a Risk Factor For Kidney Disease Progression In Sickle Cell Anemia

Blood ◽

10.1182/blood.v122.21.996.996 ◽

2013 ◽

Vol 122 (21) ◽

pp. 996-996

Author(s):

Santosh L. Saraf ◽

Xu Zhang ◽

Tamir Kanias ◽

James P. Lash ◽

Robert E. Molokie ◽

...

Keyword(s):

Steady State ◽

Kidney Disease ◽

Kidney Function ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Red Blood Cell Transfusion ◽

Free Hemoglobin ◽

Arterial Blood

Abstract Chronic kidney disease (CKD) is a frequent complication of sickle cell anemia (SCA) and is a predictor of early mortality. To determine the predictors of deteriorating kidney function in SCA, we followed 164 patients treated at the University of Illinois at Chicago for a median of 32 months (range 3-88 months). Steady-state estimated glomerular filtration (eGFR), albuminuria, and hemoglobinuria assessments were obtained at baseline and during the follow-up period. Steady-state was defined as greater than four weeks from a vaso-occlusive pain episode or a red blood cell transfusion. Hemoglobinuria was defined as positive for blood on dipstick and < 2 red blood cells on microscopy. Fifty-six (34%) of the patients had hemoglobinuria at baseline. We confirmed in a subset of 43 patients that dipstick positive hemoglobinuria (n=17) was associated with higher urine cell-free hemoglobin concentrations determined by ELISA than dipstick negative urine (n=26) (23.1 vs. 11.5 ng/mL, p<0.0001) (Figure 1). Age and mean arterial blood pressures were similar in patients with hemoglobinuria at baseline compared to those without but markers of hemolysis were higher (LDH, indirect bilirubin, AST, and reticulocyte percentage; p<0.0001). Sixty-one percent (95%CI: 48-73%) of patients with hemoglobinuria at baseline had hemoglobinuria at most recent follow up compared to 9% (95%CI: 5-18%) of patients without hemoglobinuria at baseline (p<0.0001). The proportion of patients with CKD progression defined by a 50% reduction in eGFR calculated by the CKD-EPI formula or requirement for hemodialysis or kidney transplant was higher in patients with baseline hemoglobinuria (13%, 7/56) versus without hemoglobinuria (1%, 1/108) (HR 14, 95%CI: 2-113; logrank p=0.001) (Figure 2). Progression of albuminuria category from normoalbuminuria (albuminuria < 30mg/g creatinine) to either microalbuminuria (albuminuria = 30-300 mg/g creatinine) or macroalbuminuria (albuminuria > 300mg/g creatinine) or microalbuminuria to macroalbuminuria was also higher in patients with baseline hemoglobinuria (42%, 11/26) versus without hemoglobinuria (13%, 9/67) (HR 3.1, 95%CI: 1.3-7.7; logrank p=0.004) (Figure 3). In conclusion, hemoglobinuria determined by urinalysis at steady-state is a valid assessment of increased urine cell-free hemoglobin concentration and is fairly consistent on repeat testing at steady-state visits. The presence of hemoglobinuria is significantly associated with a greater risk for progression of CKD and albuminuria. Our findings are consistent with the possibility that cell-free hemoglobin contributes to the progression of kidney disease in SCA. Further research including measures to decrease cell-free hemoglobin exposure to preserve kidney function are warranted.Figure 1Figure 1. Figure 2Figure 2. Figure 3Figure 3. Disclosures: No relevant conflicts of interest to declare.

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Sickle cell disease promotes sex-dependent pathological bone loss through enhanced cathepsin proteolytic activity

Blood Advances ◽

10.1182/bloodadvances.2021004615 ◽

2021 ◽

Author(s):

Jada M Selma ◽

Hannah Song ◽

Christian Rivera ◽

Simone Andrea Douglas ◽

Abhiramgopal Akella ◽

...

Keyword(s):

Sickle Cell Disease ◽

Bone Loss ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Bone Microarchitecture ◽

The United States ◽

Cell Disease ◽

Female Mice ◽

Blood Disorder ◽

The Impact

Sickle cell disease (SCD) is the most common hereditary blood disorder in the United States. SCD is frequently associated with osteonecrosis, osteoporosis and osteopenia and other bone related complications such as vaso-occlusive pain, ischemic damage, osteomyelitis, and bone marrow hyperplasia known as sickle bone disease (SBD)1,2. Previous SBD models have failed to distinguish the age- and sex-specific characteristics of bone morphometry. In this study, we use the Townes mouse model of SCD to study the pathophysiological complications of SBD in both SCD and sickle cell trait. Changes in bone microarchitecture and bone development were assessed by high-resolution quantitative micro-computed tomography (microCT) and the 3D reconstruction of femurs from male and female mice. Our results indicate that SCD causes bone loss and sex-dependent anatomical changes in bone. Particularly, SCD female mice are prone to trabecular bone loss while cortical bone degradation occurs in both sexes. Additionally, we describe the impact of genetic knockdown of cathepsin K and E-64 mediated cathepsin inhibition on SBD.

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