Screening for Neurocognitive Dysfunction in an Adult Population with Sickle Cell Disease

Abstract Introduction: Studies have described neuroimaging abnormalities and neurocognitive dysfunction in adults living with sickle cell anemia and no previous history of neurological impairment. At the Johns Hopkins Sickle Cell Center for Adults, we have been administering the Montreal Cognitive Assessment (MoCA) at regularly scheduled outpatient appointments as part of routine screening and clinical care. The MoCA is scored out of 30 points and consists of 28 questions grouped into seven domains of cognitive function: visual-spatial and executive, naming, attention, language, abstraction, delayed recall and orientation. While the MoCA has yet to be validated as a screening tool for cognitive impairment in adults with sickle cell disease (SCD), it has been widely used and validated in other populations to screen for mild cognitive impairment with the cutoff typically ranging from 22 to 26. The objective of this study was to describe the results of MoCA testing in a sample of adults with SCD and to explore predictors of MoCA performance using data from a retrospective chart review. Methods: A cross-sectional study was completed of the first 100 MoCAs administered to adult patients with SCD. Demographic, laboratory and clinical data were collected from each participant’s medical record up to the date that the MoCA was administered. The internal validity of each MoCA domain was analyzed using standard psychometric statistics, including a Cronbach-α score and factor analysis. Bivariate analysis was completed using Mann–Whitney U tests and Spearman Rank correlations. We identified independent predictors of MoCA performance using a multivariable robust linear regression. Age, hemoglobin and genotype were included in the multivariable analysis along with any variable found to have an association with MoCA score (p-values ≤ .10). Results: The distribution of scores is displayed in Figure 1; the mean score was 24.5 with a standard deviation of 4.1. The visual-spatial and executive function and attention domains showed strong correlation with overall test performance and demonstrated high measures of internal validity. Education, gender, weight, aspartate aminotransferase, cerebral vascular accident (CVA), chronic kidney disease (CKD) and a history of hydroxyurea therapy were associated with MoCA scores in bivariate analysis. The results of multivariable analysis are displayed in Table 1. Education was found to be a significant independent predictor of increased MoCA score, while CVA and CKD were found to be significant predictors of decreased MoCA score. When limited to the 64 participants with SS or Sβ0 Thalassemia, education and a history of hydroxyurea therapy were found to be significant independent predictors of increased score, while CKD was found to be a significant predictor of decreased score. Conclusion: A screening tool for neurocognitive dysfunction in adults with SCD is needed in order to identify those that require more definitive testing. The significant association of MoCA score with both education and CVA supports the potential validity of this measure as a screening tool in this patient population. Further validation of this tool is needed as well as an exploration into the possible relationship between improved MoCA performance and hydroxyurea use. Figure 1 Figure 1. Table 1: Multivariable Analysis Model 1: Robust Linear Regression for MoCA Score (n = 89) Independent Variables Coefficient [95% Confidence Interval] P-value Education – Completed > 12th Grade 3.1 1.5 4.7 .0003 Gender - Male 1.4 -0.13 2.8 .0738 Age (years) -0.043 -0.11 0.024 .2055 Genotype – SS or Sβ0 Thalassemia 1.3 -1.3 3.9 .3350 Hemoglobin (g/dL) 0.033 -0.62 0.69 .9196 Weight (lbs) 0.014 -0.0052 0.034 .1504 Aspartate Aminotransferase (Units/L) -0.035 -0.078 0.0090 .1179 CVA -3.3 -5.7 -0.90 .0079 CKD -3.1 -6.2 -0.056 .0460 Model 2: Robust Linear Regression for MoCA Score for participants with SS or Sβ0 Thalassemia (n = 64) Independent Variables Coefficient [95% Confidence Interval] P-value Education – Completed > 12th Grade 3.7 2.2 5.2 .0000 Gender - Male 0.95 -0.71 2.6 .2561 Age (years) -0.043 -0.13 0.046 .3363 Hemoglobin (g/dL) -0.010 -0.69 0.67 .9770 Weight (lbs) 0.0067 -0.015 0.029 .5451 Aspartate Aminotransferase (Units/L) -0.044 -0.089 0.00062 .0531 CVA -1.9 -4.7 0.92 .1832 CKD -3.4 -6.4 -0.27 .0334 History of Hydroxyurea Therapy 2.1 0.14 4.0 .0364 Disclosures Haywood: NHLBI: Research Funding. Lanzkron:NHLBI: Research Funding.

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Rapid Decline in Kidney Function in Sickle Cell Disease

Blood ◽

10.1182/blood-2018-99-117057 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1084-1084

Author(s):

Vimal K. Derebail ◽

Emily Jane Ciccone ◽

Qingning Zhou ◽

Jianwen Cai ◽

Kenneth I. Ataga

Keyword(s):

Kidney Function ◽

Sickle Cell ◽

Missing Values ◽

Multivariable Analysis ◽

Rank Test ◽

Rapid Decline ◽

Advisory Committees ◽

Survival Probabilities ◽

History Of ◽

Egfr Decline

Abstract Introduction:Chronic kidney disease (CKD) is common in sickle cell disease (SCD). We have recently reported on the progression of CKD in SCD and factors associated with it (Ciccone EJ et al, ASH, 2016). The purpose of this study was to evaluate the prevalence of rapid decline in kidney function, factors associated with such decline, and the association of rapid decline in kidney function with mortality in adult patients with SCD. Methods: We conducted a retrospective study of patients seen between July 2004 and December 2013 at an adult Sickle Cell Clinic. Patients had confirmed diagnoses of SCD, were at least 18 years old, and were in non-crisis state. We excluded patients with histories of HIV, hepatitis B and C, or systemic lupus erythematosus. Clinical and laboratory variables were obtained from medical records. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Rapid decline of kidney function was defined as eGFR loss of >3.0 ml/min/1.73 m2per year during the observation period. Logistic regression was used to model the association of rapid eGFR decline with clinical and laboratory variables, adjusting for age and sex. Multivariable analysis with variable selection was performed with backward elimination from the following initial variables - hemoglobin, reticulocyte count, lactate dehydrogenase, baseline eGFR, history of stroke, hydroxyurea therapy, systolic blood pressure, use of ACE inhibitors/angiotensin receptor blockers (ACE-I/ARB) and history of diabetes. Since proteinuria measures were missing for many patients, we performed sensitivity analyses with 1) exclusion of proteinuria, 2) inclusion of only patients with available values, 3) assignment of no proteinuria to those missing values, or 4) assignment of proteinuria to those missing values. Age- and sex- adjusted Cox proportional hazards models were used to evaluate the association of the slope of eGFR (continuous variable) or rapid decline in eGFR (binary variable) with mortality. The slope of eGFR was estimated by linear regression modeling of eGFR over time. Kaplan-Meier estimates of survival probabilities for rapid and non-rapid decline groups were obtained, and the log-rank test was used to compare the survival probabilities for the two groups. Results: Three hundred and thirty-one SCD patients with at least two eGFR measurements(SS = 218, SC = 67, Sβ0= 18, Sβ+= 22, SE = 2, SD = 2, SHPFH = 2), median age of 29 years (IQR: 20 - 41 years) were evaluated and followed for a median of 4.01 years (IQR: 1.66, 7.19). Rapid decline of eGFR (>3.0 ml/min/1.73 m2per year) was noted in 103 (31.1%) patients; 80 (33.9%) with severe genotype (HbSS/HbSβ0thalassemia) and 21 (23.6%) with mild genotype (HbSC/HbSβ+thalassemia).Baseline laboratory factors significantly associated with rapid decline in eGFR were hemoglobin (p = 0.007), ferritin (p = 0.01), and baseline eGFR (p = 0.01) (Table 1). There was a trend towards an association (p = 0.06) with baseline proteinuria (at least 1+ on dipstick urinalysis). Clinical variables significantly associated with eGFR decline were history of stroke (p = 0.002) and use of ACE-I/ARB (p = 0.006). In multivariable analysis, history of stroke (estimate: 1.07, p = 0.01) and use of ACE-I/ARB (estimate: 1.15, p = 0.01) were associated with rapid eGFR decline when proteinuria was excluded from the model or proteinuria status was assigned to those with missing values. When we limited the dataset to those with available values for proteinuria, only history of stroke (estimate: 2.00, p = 0.007) was associated with rapid decline in eGFR. Finally, we observed an association of the slope of eGFR change over time with mortality (hazard ratio [HR]: 0.99, p = 0.0002). Rapid decline in eGFR was significantly associated with increased mortality compared with eGFR decline of ≤ 3 ml/min/1.73 m2per year (HR: 2.40, p = 0.005). Kaplan-Meier estimates also showed significantly lower survival probabilities for patients with rapid eGFR decline (log-rank test; p = 0.0002) (Figure 1). Conclusion:Rapid decline in eGFR is common in SCD. Use of ACE-I/ARB and history of stroke are associated with rapid decline in renal function. Rapid decline in eGFR is associated with an increased risk of death in SCD. Long-term studies are required to determine if therapies that may reduce loss of kidney function may decrease mortality in SCD. Disclosures Ataga: Pfizer: Research Funding; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria; Modus Therapeutics: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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In Africa, a High Proportion of Adults with HbSC Meet American Society of Hematology's Eligibility Criteria for Severe Sickle Cell Disease and Starting Hydroxyurea Therapy in a Clinical Trial Setting

Blood ◽

10.1182/blood-2021-153064 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 487-487

Author(s):

William Kwesi Ghunney ◽

Eugenia Vicky Asare ◽

John Ayete-Nyampong ◽

Yvonne Adomakoh ◽

Adetola A. Kassim ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Severe Disease ◽

Incidence Rates ◽

Cell Disease ◽

Eligibility Criteria ◽

Chronic Anemia ◽

History Of ◽

Hydroxyurea Therapy ◽

Trial Setting

Abstract Introduction : Sickle cell disease (SCD), HbSC, is the second most frequent hemoglobinopathy after HbSS. Worldwide, an estimated 54,736 babies are delivered annually with HbSC disease, with the highest HbC gene frequency in West Africa (Piel et al.2013). A retrospective study at the Ghana Institute of Clinical Genetics [(GICG), a sickle cell clinic] reported that 40% of the 3,000 SCD patients attending the clinic yearly are HbSC (Asare et al.2018). HbSC disease usually results in a comparatively milder form of SCD. However, rates of maternal-fetal morbidity, retinopathy, avascular necrosis (AVN) of the hip, priapism, and chronic kidney disease are increased (Powars et al.2002; Oppong et al.2018). While microalbuminuria is lower in HbSC than HbSS, it still occurs in >23% of adults (Drawz et al.2016). In addition, thrombosis, silent cerebral infarction, sensorineural hearing loss, and pulmonary hypertension may be higher than previously suspected (Sathi et al.2019). Unlike HbSS, hydroxyurea is not routinely recommended for HbSC patients because they are all perceived to have a milder phenotype, with improved life expectancy. Thus, HbSC individuals are often excluded from randomized controlled trials in children and adults with SCD (Luchtman-Jones et al.2016). Given the high proportion of adults with HbSC in Ghana, who may benefit from hydroxyurea therapy, we tested the hypothesis that at least 5% of adults with HbSC will meet the ASH criteria for severe disease and treatment. Data indicating that a significant proportion of adults with HbSC are eligible for hydroxyurea could potentially support pilot safety trials to determine the optimal hydroxyurea dose to ameliorate symptoms while limiting toxicity. Data can also facilitate government health policy decisions to subsidize hydroxyurea costs. Methodology : We conducted a medical chart review of all adults with HbSC disease (total: 639; 18-45years) who attended the SCD clinic, GICG (January 1, 2019, to December 31, 2019). We identified a comparison group of 639 adults with HbSS, age, and gender-matched to the HbSC patients from the same clinic. Severe complications were defined as a history of ≥3 sickle cell-associated moderate to severe pain episodes/year, a history of severe acute chest syndrome (ACS), and severe symptomatic chronic anemia that interferes with daily activities or quality of life (Hydroxyurea and Transfusion Therapy for the Treatment of Sickle Cell Disease.2014). We defined acute pain episode as new onset of pain that lasts at least 4 hours, for which there is no explanation other than vaso-occlusion, which requires therapy with parenteral opioids in a medical setting (Ballas et al.2010). Severe symptomatic chronic anemia was defined as a drop in hemoglobin by ≥2g/dL below the steady state. Data were analyzed using SPSS version 23 and summarized as simple descriptive statistics. Study endpoints were the proportion of individuals with SCD who met the definition of severe disease and were eligible for hydroxyurea. We also calculated the pain and ACS incidence rates. Results: The 639 HbSC participants had a mean age of 30.8years during the one-year study period, which was identical to that of the HbSS group. At least 8.5% of HbSC adults had ≥three acute pain episodes/ year, while 1.6% had ACS. No HbSC patient had severe symptomatic chronic anemia . In total, 10.0%(64/639) of patients with HbSC disease met the eligibility criteria for hydroxyurea therapy, compared to 24.1%(154/639) of patients with HbSS, p=<0.001. The pain and ACS incidence rates for the HbSC and HbSS individuals were [74.6; 95% CI(67.9-81.3) and 2.3; 95% CI(1.2-3.5)] events per 100 patient-years vs. [123.0; 95% CI(114.4-131.6) and 5.6; 95% CI(3.8-7.5)] events per 100 patient-years respectively. Also, 1.1%(7/639), 7.7%(49/639), 0.5%(4/639), and 4.4%(11/252) of patients with HbSC had papillary necrosis, AVN, stroke, and priapism, respectively while 8.5%(54/639) of patients with HbSS had proteinuria, Table 1. Only 0.9%(HbSC) and 2.3%(HbSS) took hydroxyurea during the study period. Conclusion: Based on ASH's evidence-based guidelines, in a large SCD clinic at an academic medical center in Ghana, 10.0% of HbSC adults meet the criteria for shared decision-making to consider starting hydroxyurea therapy in a clinical trial setting. The optimal dose of hydroxyurea that maximizes benefit and minimizes toxicity in adults with HbSC is yet to be determined. Figure 1 Figure 1. Disclosures Asare: ASH Global Research Award: Research Funding.

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Functional Outcomes of Children with Sickle Cell Disease Treated for Vaso-Occlusive Painful Events.

Blood ◽

10.1182/blood.v110.11.82.82 ◽

2007 ◽

Vol 110 (11) ◽

pp. 82-82

Author(s):

Amanda M. Brandow ◽

David C. Brousseau ◽

Julie A. Panepinto

Keyword(s):

High Risk ◽

Sickle Cell Disease ◽

Linear Regression ◽

Sickle Cell ◽

Functional Outcomes ◽

Persistent Pain ◽

Cell Disease ◽

Post Discharge ◽

History Of ◽

Painful Events

Abstract Vaso-occlusive painful events lead to frequent Emergency Department (ED) visits and hospitalizations for children with sickle cell disease. After treatment to alleviate the acute pain, these children are discharged to home, however, the degree of functional impairment once children go home is not known. The objective of this study was to describe functional outcomes of children post discharge from a vaso-occlusive painful event. We conducted a prospective cohort study over a one year period of children with sickle cell disease ages 2–18 years presenting to the ED with an acute vaso-occlusive event defined as pain, acute chest syndrome or priapism. Functional outcomes were defined for this study as days of persistent pain (child and/or caretaker report), missed days of school for the child and missed days of work for the caretaker post discharge from the ED or hospital. These were assessed at both 3 and 7 days post discharge via follow-up telephone calls. Descriptive statistics were applied and linear regression was used to examine the effect of age, length of stay and history of prior vaso-occlusive events on functional outcomes post discharge. A total of 58 patients were enrolled. The mean age (SD) was 10.8 years (4.72), 52.5% were female. Genotype of sickle cell disease was 65.6% HgbSS, 24.6% HgbSC, 6.6% HgbSB+thal, and 3.3% other. There were 23% of patients discharged from the ED. Mean length of stay (SD) was 2.16 days (1.83). There were 24.1% of patients who had 3 or more hospitalizations for vaso-occlusive painful events in the year prior to study entry. Functional outcomes post discharge for all patients revealed that both child and caretaker on average missed more than one day of work and children had more than two days of persistent pain (Table 1). Subgroup analysis showed that patients with frequent prior vaso-occlusive events had significantly worse outcomes in regards to days of persistent pain and missed days of school post discharge (Table 1). Of those children attending school, 28.6% missed 3 or more days of school post discharge. Of those caretakers working, 9.1% missed 3 or more days of work post discharge. Persistent pain was reported by 15.5% of children at 5 or more days post discharge. Linear regression showed that a history of frequent vaso-occlusive painful events predicted worse functional outcomes (p=0.0067). Vaso-occlusive painful events have an enormous functional impact post discharge on both the child and family. Children with a history of frequent vaso-occlusive painful events have worse functional outcomes, and are therefore a high risk patient group. Since vaso-occlusive painful events are the most common complications of sickle cell disease, interventions to improve functional outcomes at home in the post discharge period are imperative for all patients with sickle cell disease and in particular this high risk group. Table 1. Functional Outcomes Outcome All Patients (n=58)* Patients with < 3 Prior Vaso-occlusive Events (n=44)*† Patients with ≥ 3 Prior Vaso-occlusive Events (n=14)*† Comparison of Means between <3 and ≥ 3 Prior Vaso-occlusive Events§ *Mean ± Standard Deviation; †In year prior to study entry; §Student’s t-test Missed Days of School/Work Child (school) 1.83 (±1.32) 1.61 (±1.07) 3.6 (±1.34) p=0.001 Caretaker (work) 1.15 (±1.20) 1.28 (±1.28) 1.0 (±0.89) p=0.617 Days of Persistent Pain 2.53 (±2.01) 2.0 (±1.41) 3.86 (±2.63) p=0.023

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Genetic Modifiers Identify a High Risk Group for Stroke in Three Independent Cohorts of Sickle Cell Anemia Patients

Blood ◽

10.1182/blood.v128.22.1015.1015 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1015-1015

Author(s):

Santosh L. Saraf ◽

Titilola S. Akingbola ◽

Binal N. Shah ◽

Xu Zhang ◽

Lewis L. Hsu ◽

...

Keyword(s):

High Risk ◽

Sickle Cell ◽

Research Funding ◽

Risk Group ◽

Linear Trend ◽

Hemoglobin Concentration ◽

High Risk Group ◽

Genetic Modifiers ◽

History Of ◽

Hydroxyurea Therapy

Abstract Two common genetic modifiers, α-thalassemia and the BCL11A rs1427407 T allele, are observed in approximately one-third of patients with sickle cell anemia (SCA) and are associated with reduced hemolysis and higher hemoglobin F (HbF) levels, respectively. We investigated the laboratory and clinical effects of α-thalassemia and the BCL11A rs1427407 T allele in the University of Ibadan cohort of SCA patients and replicated our findings in two independent SCA cohorts, University of Illinois at Chicago (UIC) and Walk-Treatment of Pulmonary Hypertension and Sickle cell disease with Sildenafil Therapy (Walk-PHaSST). Alpha-thalassemia status was determined by PCR in all 3 cohorts while the BCL11A rs1427407 genotype was determined by PCR in the Ibadan and UIC cohorts and imputed in the Walk-PHaSST cohort. Comparisons according to genotype were performed using the linear trend test for continuous variables and Cochran's test of linear trend for categorical variables. Alpha-thalassemia was observed in 43% of 257 SCA patients from Ibadan and was associated with higher body mass index and lower white blood cell count (Table 1). The BCL11A rs1427407 T allele was observed in 46% of SCA patients from Ibadan and was associated with higher hemoglobin concentration. HbF levels by HPLC were available in 25 patients (12 with the BCL11A rs1427407 T allele) enrolled in a study of low-dose hydroxyurea; these levels were higher in patients with at least one rs1427407 T allele at baseline and progressively during therapy with hydroxyurea 10 mg/kg/day (repeated measures P=0.01). We defined a high risk genetic group as the absence of α-thalassemia in combination with absence of the BCL11A rs1427407 T allele. This high risk group was observed in 31% of SCA patients from the Ibadan cohort and was associated with a higher reticulocyte percentage (15.0% vs. 7.8%, P=0.08) and a higher prevalence for a history of stroke (6% vs. 1%, P=0.02). The association with stroke history persisted on logistic regression analysis after adjusting for age, gender, and hydroxyurea therapy (OR 9.4, 95%CI: 1.2-72.8; P=0.03). We then replicated the association of this high risk group with markers of hemolysis and with history of stroke in the UIC and Walk-PHaSST SCA cohorts. In the UIC cohort, the high risk group was observed in 34% (92/271) and was also associated with higher reticulocyte counts (13.5% vs. 11.9%, P=0.10) and higher prevalence for stroke history (33% vs. 22%; age, gender, HU-adjusted OR 1.7, 95%CI: 1.0-3.0; P=0.066). In the Walk-PHaSST cohort, this high risk profile was observed in 38% (149/394) and was associated with a higher reticulocyte percentage (9.7% vs. 8.4%, P=0.0005), lower hemoglobin concentration (8.4 vs. 8.8 g/dL; P=0.017), and higher prevalence for stroke history (15% vs. 6%; age, gender, HU-adjusted OR 2.6, 95%CI: 1.3-5.3; P=0.007). In conclusion, a high risk group of SCA patients, defined by the lack of the protective α-thalassemia and the BCL11A rs1427407 variants, is associated with a higher degree of hemolysis and a higher prevalence of stroke history on cross sectional analysis in three independent cohorts. This high-risk profile may help identify patients to prioritize for hydroxyurea therapy and for closer monitoring strategies for stroke. Disclosures Hsu: Sancilio: Research Funding; Astra Zeneca: Consultancy, Research Funding; Purdue Pharma: Research Funding; Gerson Lehman Group: Consultancy; Eli Lilly: Research Funding; Centers for Medicare and Medicaid Innovation: Research Funding; Hilton Publishing: Consultancy, Research Funding; Mast Therapeutics: Research Funding; EMMI Solutions: Consultancy; Pfizer: Consultancy, Research Funding.

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Use of a Computer Based Neurocognitive Software Program in Asymptomatic Neurologically Intact Adults with Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.1524.1524 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1524-1524 ◽

Cited By ~ 1

Author(s):

Regina D. Crawford ◽

Miriam Feliu ◽

Christopher L. Edwards ◽

Marilyn J. Telen

Keyword(s):

Cognitive Flexibility ◽

Sickle Cell ◽

Screening Tool ◽

Vital Signs ◽

Neurocognitive Deficits ◽

Cell Disease ◽

History Of ◽

Computer Based ◽

Percentile Scores ◽

Neurologically Intact

Abstract Abstract 1524 Poster Board I-547 Incidence of stroke in sickle cell disease (SCD) is approximately 11% under the age of 20, and 24% of patients have had a stroke by age 45. In children with SCD, 24% with no history of stroke are found to have neurocognitive deficits and silent infarcts. At least 20% of adults with SCD and no history of stroke also have an abnormal MRI, and up to 63% have either an abnormal MRI or neurocognitive dysfunction. However, formal neurocognitive testing can be difficult to obtain, especially in adults, as it is costly, time-consuming, and requires specialized expertise. An office-based screening tool would therefore be beneficial in this population. CNS Vital Signs™ (CNS-VS) is a computer-based software program designed to evaluate neurocognitive deficits based on traditional neuropsychological testing. The test reports an overall score referred to as the neurocognitive index (NCI), as well as scores based on seven domains: verbal memory, visual memory, finger tapping, symbol digit coding, Stroop test, shifting attention, and continuous performance test. The domains reflect areas of memory, psychomotor speed, reaction time, cognitive flexibility and complex attention. We conducted a pilot study in neurologically intact adults with SCD (HbSS or Sβ0 thalassemia) using CNS-VS as an office-based computer-administered tool for possible screening of patients with SCD for subtle neurocognitive impairment. SCD subjects were recruited from the Duke adult sickle cell clinic. Age, sex, and race matched controls were recruited by word of mouth. Each subject also underwent screening tests for severe depression and cognitive limitations using the mini mental status exam (MMSE) and the depression dejection score (DDS) from the Profile of Moods Survey. Patients also completed a perceived stress survey. Subjects with SCD were excluded if they had a recent hospitalization for pain within three weeks prior to enrollment, history of stroke or TIA, DDS score >40, or MMSE score <20. Controls were excluded with the same DDS/MMSE scores, history of stroke or TIA, or history of sickle trait. Thirty subjects were enrolled in this pilot study, 24 patients with SCD and 6 controls. Seventeen patients were male, 13 female, and 23 of 24 patients had HbSS. Twenty-seven subjects were right hand dominant and 3 left hand dominant, and all subjects were of African-American descent. Mean age for the controls was 43.54 yrs ± 4.24, and for the SCD group 34 yrs ± 2. The mean years of education (including primary) was 15 years for both SCD patients and controls. Mean baseline Hb and Hct values among SCD patients were 8.11 ± 0.29 g/dL and 23.97 ± 0.92 and 13.48 ±1.15 g/dL and 40.60 ± 3.11 for controls. Scores on the MMSE, DDS, and perceived stress survey were not statistically different between the controls and SCD patients. Using CNS-VS, no difference was found in scores in areas of memory, reaction time, cognitive flexibility, and complex attention between SCD patients and controls. However, psychomotor standard and percentile scores were statistically different (p=0.02) between SCD patients and controls. The symbol digit coding domain also showed statistical significance (p=0.001) between the groups for both standard and percentile scores. In SCD patients, Hb was significantly correlated with NCI standard and percentile scores (p < 0.0001). Reticulocyte count, lactate dehydrogenase level, total bilirubin, and creatinine level did not show any correlation with NCI scores. Symbol digit coding appeared to be the most sensitive of the tests, although psychomotor performance also differed significantly compared to controls. Decreased cognitive and psychomotor performance can reflect either localized or diffuse brain damage. The impact of medications, mild depression, and pain may also explain differences between the groups. Therefore, we believe that CNS Vital Signs™ is a promising screening tool for subtle neurocognitive deficits in asymptomatic neurologically intact adults with SCD. Our findings need to be validated in a larger cohort, along with correlation of scores with MRI results and expansion of testing to include patients with other variants of SCD. Disclosures No relevant conflicts of interest to declare.

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Tract‐specific analysis and neurocognitive functioning in sickle cell patients without history of overt stroke

Brain and Behavior ◽

10.1002/brb3.1978 ◽

2021 ◽

Author(s):

Yaqiong Chai ◽

Chaoran Ji ◽

Julie Coloigner ◽

Soyoung Choi ◽

Melissa Balderrama ◽

...

Keyword(s):

Sickle Cell ◽

Neurocognitive Functioning ◽

Specific Analysis ◽

History Of

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Severe COVID-19 with acute respiratory distress syndrome (ARDS) in a sickle cell disease adult patient: case report

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01412-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marion Teulier ◽

Alexandre Elabbadi ◽

Grigorios Gerotziafas ◽

François Lionnet ◽

Guillaume Voiriot ◽

...

Keyword(s):

Sickle Cell ◽

Case Reports ◽

Cor Pulmonale ◽

Point Of View ◽

Nasopharyngeal Swab ◽

Prevention Policy ◽

Cord Injury ◽

History Of ◽

Pulmonary Arterial ◽

Venovenous Ecmo

Abstract Background Sickle-cell anaemia is a widespread genetic disease prevalent worldwide among African and African-American populations. The pathogenesis is most often revealed by pulmonary conditions, including acute thoracic syndrome, which is affecting the life expectancy of these populations. The global spread of CoV2-SARS infection with a respiratory tropism, endothelial damages and procoagulant status endangers the SCD population. However, with only a few case reports, consequences of the Covid-19 pandemic on SCD population remain poorly known. Case presentation We report a case of a 33-year-old man with a history of homozygous SS homozygous sickle cell anemia who consulted on March 24, 2020 for febrile dyspnea 11 days after the onset of symptoms. A nasopharyngeal swab was positive for SARS-CoV-2. His respiratory status worsened rapidly in the emergency room and then in ICU leading to severe ARDS requiring intubation, curarization, and venovenous ECMO. Hematologically, severe hemolysis associated with major thrombocytopenia without documented spinal cord injury was noted. Several transfusion exchanges are performed. The evolution was finally slowly favorable and led to discharge from the intensive care unit and then from the hospital. Conclusions This case recalls the importance of an increased prevention policy against COVID-19among the SCD population. In addition, from a therapeutic point of view, it advocates (1) a high preventive anticoagulation from the outset according to the level of D-dimers (2) the use of venovenous ECMO in this particular case, whereas this technique has had rather disappointing results in acute chest syndromes. (3) Unexpectedly, our patient did not develop pulmonary arterial hypertension (PAH) and acute cor pulmonale (ACP), whereas this is a common feature of ARDS during SCD. These last two observations suggest a different pathophysiology of pulmonary disorders in SCD patients in the case of SARS COv2. It could be associated with marked hypoxemia secondary to pulmonary vascular vasodilation.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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Older trauma patients are at high risk of delirium, especially those with underlying dementia or baseline frailty

Trauma Surgery & Acute Care Open ◽

10.1136/tsaco-2020-000639 ◽

2021 ◽

Vol 6 (1) ◽

pp. e000639

Author(s):

Danielle Ní Chróinín ◽

Nevenka Francis ◽

Pearl Wong ◽

Yewon David Kim ◽

Susan Nham ◽

...

Keyword(s):

Older Patients ◽

Multivariable Analysis ◽

Primary Outcome Measure ◽

Hospital Length ◽

Assessment Tools ◽

Hospital Length Of Stay ◽

Trauma Patients ◽

Level Of Evidence ◽

Increased Risk ◽

History Of

BackgroundGiven the increasing numbers of older patients presenting with trauma, and the potential influence of delirium on outcomes, we sought to investigate the proportion of such patients who were diagnosed with delirium during their stay—and patient factors associated therewith—and the potential associations between delirium and hospital length of stay (LOS). We hypothesized that delirium would be common, associated with certain patient characteristics, and associated with long hospital LOS (highest quartile).MethodsWe conducted a retrospective observational cohort study of all trauma patients aged ≥65 years presenting in September to October 2019, interrogating medical records and the institutional trauma database. The primary outcome measure was occurrence of delirium.ResultsAmong 99 eligible patients, delirium was common, documented in 23% (23 of 99). On multivariable analysis, adjusting for age, frailty and history of dementia, frailty (OR 4.09, 95% CI 1.08 to 15.53, p=0.04) and dementia (OR 5.23, 95% CI 1.38 to 19.90, p=0.02) were independently associated with likelihood of delirium. Standardized assessment tools were underused, with only 34% (34 of 99) screened within 4 hours of arrival. On univariate logistic regression analysis, having an episode of delirium was associated with long LOS (highest quartile), OR of 5.29 (95% CI 1.92 to 14.56, p<0.001). In the final multivariable model, adjusting for any (non-delirium) in-hospital complication, delirium was independently associated with long LOS (≥16 days; OR 4.81, p=0.005).DiscussionIn this study, delirium was common. History of dementia and baseline frailty were associated with increased risk. Delirium was independently associated with long LOS. However, many patients did not undergo standardized screening at admission. Early identification and targeted management of older patients at risk of delirium may reduce incidence and improve care of this vulnerable cohort. These data are hypothesis generating, but support the need for initiatives which improve delirium care, acknowledging the complex interplay between frailty and other geriatric syndromes in the older trauma patients.Level of evidenceIII.

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Concurrent Bilateral Central Retinal Artery Occlusion Secondary to Sickle Cell Crisis

Journal of Investigative Medicine High Impact Case Reports ◽

10.1177/23247096211028392 ◽

2021 ◽

Vol 9 ◽

pp. 232470962110283

Author(s):

Gowri Renganathan ◽

Piruthiviraj Natarajan ◽

Lela Ruck ◽

Roberto Prieto ◽

Bharat Ved Prakash ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Vision Loss ◽

Central Retinal Artery Occlusion ◽

Retinal Artery Occlusion ◽

Artery Occlusion ◽

Cell Disease ◽

Sickle Cell Crisis ◽

History Of ◽

Retinal Artery

Vascular occlusive crisis with a concurrent vision loss on both eyes is one of the most devastating disability for sickle cell disease patients. Reportedly occlusive crisis in the eyes is usually temporary whereas if not appropriately managed can result in permanent vision loss. A carefully managed sickle cell crisis could prevent multiple disabilities including blindness and stroke. We report a case of a 24-year-old female with a history of sickle cell disease who had acute bilateral vision loss during a sickle crisis and recovered significantly with a timely emergent erythrocytapheresis.

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