Impact of Jaundice On Adults with Sickle Cell Anemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4753-4753
Author(s):  
Alecia C. Nero ◽  
Timothy L. McCavit ◽  
Leah M. Adix ◽  
Bonnie L. Davis ◽  
Beena S. Mathew ◽  
...  
Keyword(s):  
Treatment Group ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Assessment Tools ◽  
Treatment Groups ◽  
Disease Modifying Therapy ◽  
Study Results ◽  
Disease Modifying ◽  
The Impact

Abstract Abstract 4753 Introduction For many patients with sickle cell anemia (SCA), jaundice, yellow discoloration of the skin and mucous membranes, may be the most visible manifestation of their disease. The degree to which jaundice impacts the daily lives of patients with SCA has not been previously described. This study aims to assess the effect of jaundice on the health-related quality of life (HRQOL) of adults living with SCA. Methods This study was a cross-sectional survey of patients with SCA. A convenience sample of patients age > 17 years with SCA were approached during routine clinic visits to Parkland Memorial Hospital or UT Southwestern University Hospitals. Consenting patients completed a 15 question survey instrument. The survey was divided into three subscales (personal, relational, and behavioral) where individual items were presented in a 5-point Likert scale. This instrument was reviewed by non-study hematologists, nurses and patients for face validity. No other assessment of reliability or validity was performed. Additional data collected included serum total bilirubin (TB), hemoglobin, reticulocyte count (%) and patient self-report of current treatment for SCA (hydroxyurea [HU], chronic blood transfusions, or other). We tested for associations between survey subscales and TB, reticulocyte count, or hemoglobin using Spearman correlation coefficients. We compared the Spearman correlations of the survey subscales and TB between treatment and non-treatment groups using the Fisher's z transformation. Gender and age adjustments were made using linear regression. TB was transformed by natural log for regression analysis. Results We surveyed 100 subjects (58% female) with SCA. The median age was 25 years (range: 18–63), and the median TB was 2.5 mg/dL (range: 0.4–13.8). Nearly half of patients reported receiving treatment with 28% on HU and 14% on chronic transfusions. The majority of patients reported a history of jaundice, with 79% listing responses of ‘sometimes’, ‘often’, or ‘always’. Summary results for the remainder of the survey are listed in the table. TB was positively correlated with the 3 subscales (personal, r=0.32, p=0.002; relational, r=0.38, p=0.0002; behavioral, r=0.31, p=0.003). We compared these correlations between ‘treatment’ and ‘no treatment’ groups and observed strong correlations in the ‘no treatment’ group (personal, r=0.55, p<0.0001; relational, r=0.63, p<0.0001; behavioral, r=0.52, p=0.0002). TB was not correlated with the subscales in the ‘treatment’ group. After adjusting for age, gender, and disease-modifying therapy, the three subscales were associated with TB (personal, β = 0.066, 95% Confidence Interval (CI) [0.027, 0.104], p=0.001; relational, β = 0.061, 95% CI [0.031, 0.092], p=0.0001; behavioral, β = 0.104, 95% CI [0.045, 0.164], p=0.0009). Conclusion Jaundice negatively impacts the lives of many adults with SCA. The personal and relational subscales suggest more impact on the self-image of respondents, but only a few reported behavioral changes. The impact of jaundice appears to be mitigated by disease-modifying therapy for SCA (HU or chronic transfusions); however, this study was not created to determine the effectiveness of these reported treatments. Despite the fact this instrument was not validated, our study results suggest jaundice should be well-represented in HRQOL assessment tools in adults with SCA. Moreover, prospective studies are needed to clarify potential benefits of disease-modifying therapies, particularly HU, on the burden of jaundice in SCA. Disclosures: Buchanan: HemaQuest Pharmacuetical, Inc.: Research Funding.

scholarly journals Hydroxyurea reduces cerebral metabolic stress in patients with sickle cell anemia

Blood ◽  
2019 ◽  
Vol 133 (22) ◽  
pp. 2436-2444 ◽  
Author(s):  
Melanie E. Fields ◽  
Kristin P. Guilliams ◽  
Dustin Ragan ◽  
Michael M. Binkley ◽  
Amy Mirro ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Metabolic Stress ◽  
Brain Magnetic Resonance Imaging ◽  
Border Zone ◽  
Oxygen Extraction Fraction ◽  
Transfusion Therapy ◽  
Whole Brain ◽  
Disease Modifying Therapy ◽  
Disease Modifying

Abstract Chronic transfusion therapy (CTT) prevents stroke in selected patients with sickle cell anemia (SCA). We have shown that CTT mitigates signatures of cerebral metabolic stress, reflected by elevated oxygen extraction fraction (OEF), which likely drives stroke risk reduction. The region of highest OEF falls within the border zone, where cerebral blood flow (CBF) nadirs; OEF in this region was reduced after CTT. The neuroprotective efficacy of hydroxyurea (HU) remains unclear. To test our hypothesis that patients receiving HU therapy have lower cerebral metabolic stress compared with patients not receiving disease-modifying therapy, we prospectively obtained brain magnetic resonance imaging scans with voxel-wise measurements of CBF and OEF in 84 participants with SCA who were grouped by therapy: no disease-modifying therapy, HU, or CTT. There was no difference in whole-brain CBF among the 3 cohorts (P = .148). However, whole-brain OEF was significantly different (P &lt; .001): participants without disease-modifying therapy had the highest OEF (median 42.9% [interquartile range (IQR) 39.1%-49.1%]), followed by HU treatment (median 40.7% [IQR 34.9%-43.6%]), whereas CTT treatment had the lowest values (median 35.3% [IQR 32.2%-38.9%]). Moreover, the percentage of white matter at highest risk for ischemia, defined by OEF greater than 40% and 42.5%, was lower in the HU cohort compared with the untreated cohort (P = .025 and P = .034 respectively), but higher compared with the CTT cohort (P = .018 and P = .029 respectively). We conclude that HU may offer neuroprotection by mitigating cerebral metabolic stress in patients with SCA, but not to the same degree as CTT.

scholarly journals The Grndad Registry: Contemporary Natural History Data and an Analysis of Real-World Patterns of Use and Limitations of Disease Modifying Therapy in Adults with SCD

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-36
Author(s):  
Alexandra Boye-Doe ◽  
Elizabeth Brown ◽  
Charu Puri-Sharma ◽  
Anjulika Chawla ◽  
Joshua J Field ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Real World ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Reticulocyte Count ◽  
Principal Investigator ◽  
Advisory Committees ◽  
Disease Modifying Therapy ◽  
Disease Modifying ◽  
The Impact

Incremental improvement in care for children with sickle cell disease (SCD), arising from government-funded research over the last 4 decades, resulted in a dramatically reduced childhood mortality. However, the impact of iterative research and disease modifying therapy (DMT) on adults with SCD has not been as strong. Until now, there has been no coordinated, longitudinal, generalizable, natural history study of SCD that allowed for an assessment of the contemporary adult population. Here, we describe demographics at enrollment and cross-sectional clinical characteristics of 570 adults with SCD (SCA, homozygous HbSS or HbSb0 N=387, 68%, and compound heterozygous SCD variant, HbSC or HbSb+ N=183, 32%, Table I) on whom we have evaluable data. These data are from the multi-site REDCap-based prospective Globin Research Network for Data and Discovery (GRNDaD) registry, comprising 11 centers with over 1100 consented adults and children. The objective of this work was to evaluate the cohort at year of entry, including the use and clinical associations with DMT, and to explore indicators of disease progression as patients age. 16% of adults with SCA and 9.6% with variant disease stroke; 60.9% of adults with SCA and 41% with variant disease had a history of acute chest syndrome. Albuminuria was prevalent in both SCA (39.5%) and variant disease (19.4%). 185 adults (185/387, 47.8%) with SCA, previously referred for symptoms in clinic, had recorded tricuspid regurgitant jet velocity measurements, with a significantly abnormal result (&gt;2.7 m/s), in 92 (92/185, 49.7%). At enrollment, 45% of adults with SCA (175/387) and 14% of adults with variant disease (25/183) were on hydroxyurea (HU); 20.4% of adults with SCA were on chronic transfusions (79/387) compared with 7% of adults with variant disease (13/183). One third of all adults with SCA were not on or were not consistently on DMT, and had laboratory evidence for increased hemolysis (Table 1). Adults with SCA who were on HU had a higher MCV and higher HbF than other treatment states (Table 1). However, only 34% (60/175) of adults with SCA on HU were at maximally tolerated dose (MTD), per guideline-based recommendations, i.e. ANC ≤4.0 x109/L. On HU, those in the lowest quartile for ANC (&lt;3.2 x109/L) were older (mean age 35.9 years (95% Confidence Limit (CL) 32.5-39.3) vs. 31.2 (95% CL 28.2 to 34.4) years, P=0.04), had a lower mean reticulocyte count (119 x109/L (95% CL 76-162) vs. 203 (95% CL 129-278), P=0.05), and a higher mean MCV (104.4 fL (95% CL 100.2-108.7) vs. 92.5 (95% CL 87.2-97.8), P=0.0007), compared to those in the highest quartile for ANC (&gt;5.7 x109/L, N=34), but did not otherwise differ (including mean HbF, which was not measured in a standardized way). In older adults with SCD (Table 2), fewer people with SCA than with variant disease were &gt;54 years old, (26/387 HbSS, 7%, vs. 34/183, 19%, respectively). The older adult with SCA had a depressed reticulocyte count and a trend towards a higher creatinine. 45% of adults with SCA were on HU, and only a minority were at MTD, highlighting the challenges to optimal long-term therapy in chronic illness. Those patients not stably on DMT had laboratory evidence for worse anemia and hemolysis, without an evident increase in hospital admissions, perhaps due to a hyper hemolytic phenotype. Despite a more intensive regimen, SCA patients on transfusions had a higher Hgb but did not have hemolysis labs that differed from SCA patients on HU. Further, there was no difference in hospitalizations amongst treatments for SCA, although a decrease in hospitalizations was detectable in variant disease (Table 1). Successful use of DMTs in SCA was challenging even in academic centers, and there was evidence for ongoing hemolysis in treated and untreated patients. These real world data provide useful information about adults (&gt;17 years) with SCD. These data highlight opportunities to improve adherence to therapy (patient-centered) and to prescribing guidelines (provider-centered), and to consider less-burdensome alternatives. Importantly, we found that a large proportion of people with SCA were not on DMT, and with HU often not at MTD. In future, the GRNDaD registry will enable prospective longitudinal real-world analyses of the impact of DMTs and/or newer therapies on clinical outcomes, will enhance quality improvement, and will allow us to more fully explore clinical characteristics, of SCA and variant disease, in the aging adult. Disclosures Puri-Sharma: Bluebird Bio: Current Employment. Chawla:Bluebird Bio: Current Employment. Field:Shires: Research Funding; Ironwood: Research Funding. Neumayr:Emmaus: Consultancy; Bayer: Consultancy; CTD Holdings: Consultancy; Pfizer: Consultancy; ApoPharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Micelle: Other: Site principal investigator; GBT: Other: Site principal investigator; PCORI: Other: site principal investigator; Novartis: Other: co-investigator; Bluebird Bio: Other: co-investigator; Sangamo Therapeutics: Other; Silarus: Other; Celgene: Other; La Jolla Pharmaceuticals: Other; Forma: Other; Imara: Other; National Heart, Lung, and Blood Institute: Other; Health Resources and Services Administration: Other; Centers for Disease Control and Prevention: Other; Seattle Children's Research: Other. Desai:Pfizer, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; GBT, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Rockpointe Continuing Medical Education Company: Consultancy. Lanzkron:GBT: Research Funding; HRSA: Research Funding; Ironwood: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Pfizer: Research Funding; Pharmacy Times Continuing Education: Honoraria; Prolong: Research Funding. Little:Hemex Health, Inc.: Patents & Royalties: Microfluidic electropheresis (patent, no royalties); BioChip Labs: Patents & Royalties: SCD Biochip (patent, no royalties); GBT: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Research Funding; NHLBI: Research Funding.

Antioxidant Vitamins C and E Supplementation Does Not Improve the Hemolytic Profile of Sickle Cell Anemia Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1063-1063
Author(s):  
Martha Mariana A S Arruda ◽  
Grazielle Mecabo ◽  
Celso Arrais Rodrigues ◽  
Sandra S Matsuda ◽  
Iara Baldim Rabelo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Uric Acid ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Antioxidant Vitamins ◽  
Vitamin Supplementation ◽  
Indirect Bilirubin ◽  
Severe Deficiency ◽  
The Impact

Abstract Abstract 1063 Background: Erythrocytes of sickle cell anemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells, and oxidative stress seems to play a significant role in the pathophysiology of this disease. In erythrocytes, oxidative stress primarily affects the membrane and results in hemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants, which could prevent adhesion and phagocytosis of oxidized erythrocytes. Aims: To evaluate the impact of antioxidant vitamins C (vitC) and E (vitE) supplementation in the hemolytic profile in SCA patients. Patients and methods: Homozygous SCA or S-β-thalassemia patients, over 18 years, were randomly assigned to receive VitC 1,400 mg + VitE 800 mg per day or placebo, administered orally for 180 days. Pregnant women and patients with iron overload out of chelation therapy were excluded. Patients were evaluated clinically and blood samples were collected at days 0 and 180 for complete blood count, automated reticulocyte count, indirect bilirubin, lactate dehydrogenase (LDH), haptoglobin, uric acid, and serum levels of VitC and VitE. Results: Overall, 83 patients were enrolled (44 vitamins, 39 placebo). The median (range) age was 27 (18–68) years, and 53 (64%) were female. There were no significant differences between the two groups as regards clinical complications of SCA or baseline laboratorial tests and serum vitC and vitE. Sixty percent of the patients were VitC deficient (30% with severe deficiency), 70% were VitE deficient (33% with severe deficiency) and 44% were deficient in both vitamins. Vitamin supplementation increased VitC from 27.2 to 62.6 μMol/L (p<0.0001) and VitE from 13.9 to 20.2 μMol/L (p<0.0001). No changes in vitC or vitE were observed in patients receiving placebo. No significant changes in hemoglobin levels, hematocrit, mean corpuscular volume were observed in either group. However, patients receiving vitamin supplementation presented a significant increase in the median reticulocyte count (from 152 to 195 ×106/μL, p=0.01), LDH (from 396 to 425 U/L, p=0.018), indirect bilirubin (from 1.45 to 1.73 mg/dL, p<0.0001), and uric acid (from 4.75 to 5.15 mg/dL, p=0.02), and a decrease in the haptoglobin levels (from 3.95 to 3.45 mg/dL, p=0.06). Conclusion: Supplementation with vitamins C and E did not improve anemia and, surprisingly, increased markers of hemolysis in patients with SCA and S-β-thalassemia. The exact mechanisms to explain our findings and their clinical significance remain to be determined. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Radiological Findings By Magnetic Resonance (MRI) and Arteriography (MRA) Brain Imaging Compared to Neurological, Stroke and TCD Assessment in Children with Sickle Cell Anemia in Uganda

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2304-2304
Author(s):  
Amelia Boehme ◽  
Richard Idro ◽  
Deogratias Munube ◽  
Paul Bangirana ◽  
Ezekiel Mupere ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Mr Imaging ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Evidence ◽  
Sub Saharan Africa ◽  
Disease Modifying Therapy ◽  
Disease Modifying ◽  
Large Infarct ◽  
Small Infarct

Background: Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations of children with SCA in sub-Saharan Africa are limited, especially magnetic resonance imaging and angiography (MRI/MRA). In a sample of Ugandan children receiving care at the Mulago Hospital sickle cell clinic in Kampala and were not on disease-modifying therapy, we examined the range of MR imaging findings, and how those findings correlated with standardized demographic, clinical, neurological and neurocognitive assessments. Methods: From within a larger sample of 265 participants with HbSS ages 1-12 years not taking disease-modifying therapy and enrolled in the BRAIN SAFE study, a sub-sample of 81 underwent non-contrast MRI/MRA on a 1.5 Telsa scanner. Participants also underwent 3 standardized assessments: neurocognitive testing by experienced testers using the Mullen Scales of Early Learning (for ages 1-4 years) or Kaufman Assessment Battery for Children, 2nd edition (for ages 5-12) (abnormal z-score of -2 or lower), stroke examination (PedsNIHSS) and transcranial Doppler ultrasound (TCD) using criteria for pediatric SCA. Participants undergoing MRI/MRA intentionally included 29 without any abnormal findings. MRI scans included T1- and T2- weighted images, T2 FLAIR and MRA three-dimensional time-of-flight technique. MR scans were interpreted by clinical and research methods, the latter per SWiTCH protocol (Helton, Blood 2014). Adjudication of differing reads was performed by a blinded third neuroradiologist. Results: A total of 81 children with SCA were examined by MRI/MRA. Mean age was 6.48 ± 2.75 years; 50.6% were male. Mean hemoglobin was 7.26±0.90 g/dl; 75% had hemoglobin <8.0. In all, 16.7% were malnourished using standard international measures established by age and sex. Infarcts and/or arterial stenoses on MRI/MRA were detected in 42 (52%), including 13 (25%) with no other abnormalities detected. There were 35 children (43.2%) who had medium or large infarcts seen; an additional 16 (19.8%) had 1-2 small infarcts. Four had moya moya. Of the 29 children categorized as normal on each of the 3 other tests, 14 (48.3%) had one or more medium or large infarct(s) on MRI, and 3 (10.3%) had 1-2 small infarcts (Figure 1). The proportion of children with malnutrition was higher among those with an abnormal MRI compared to those with a normal MRI, whereas no children with a small infarct was malnourished (29.4% vs. 10.7% vs. 0% p=0.019). A higher proportion of participants with stroke by exam had medium or large infarct(s) compared to participants with normal or small infarct (28.6% vs. 10% vs. 6.3%; p=0.061). Stroke on exam was associated with medium or large infarct(s) compared to normal or small infarct (unadjusted OR 4.2; 95% CI 1.19-14.8), and remained after adjusting for age and hemoglobin (OR 3.90 95%CI 1.10-13.9). The proportion of abnormal psychological testing was higher in the small infarct group than in the group with larger infarct(s) or the normal group (37.5% vs. 28.6% vs. 17.2%; p=0.307). Conclusion: High prevalence of pediatric cerebral vasculopathy was found on MR scanning. Despite clinical evidence suggesting abnormal neuropsychological testing or a prior stroke, not all of the children who had clinical evidence of neurological disorders had MRI evidence of a stroke. Additionally, a number with no evidence of stroke had infarct(s) on MRI, so-called "silent stroke." The strongest predictors of an abnormal MRI reading included having a detectable stroke or an abnormal TCD. MR imaging is a critical aspect of evaluating cerebral vasculopathy in this patient population, and will be an important measure when prospectively assessing impact in a treatment trial. Disclosures No relevant conflicts of interest to declare.

Prognostic Significance of Early Vaso-Occlusive Complications in Children Who Have Sickle Cell Anemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3176-3176
Author(s):  
Charles T. Quinn ◽  
Elizabeth P. Shull ◽  
Naveed Ahmad ◽  
Zora R. Rogers ◽  
George R. Buchanan
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Strong Predictor ◽  
Prognostic Significance ◽  
Adverse Outcomes ◽  
Acute Chest Syndrome ◽  
Disease Modifying Therapy ◽  
Pain Crisis ◽  
Disease Modifying

Abstract Sickle cell anemia (SS) is a phenotypically variable disease whose course is difficult to predict. The Cooperative Study of Sickle Cell Disease (CSSCD) found that dactylitis in the 1st year of life predicted adverse outcomes in later childhood. We aimed to determine whether early vaso-occlusive complications, including dactylitis, were prognostic in the Dallas Newborn Cohort. We studied all cohort members with SS or sickle-β0-thalassemia who were &lt;1 yr of age at their first clinic visit, ≥5 yrs of age at last follow-up, and who had complete records. We defined 3 potential “early” (occurring in the first 3 yrs of life) predictors: any hospitalization for (1) pain crisis (non-dactylitis), (2) dactylitis, or (3) acute chest syndrome (ACS). We studied the associations of these predictors with the following “late” (occurring on or after the 3rd birthday) outcomes: death of any cause; overt stroke; use of hydroxyurea (HU), chronic transfusion (CT), or stem cell transplantation (SCT); and mean number of hospitalizations for late pain crisis and ACS. Late pain and ACS episodes were enumerated for each patient between the 3rd birthday and the last clinical encounter or the start date of a disease-modifying therapy (HU, CT, or SCT), whichever was first. Mean number of pain and ACS events was analyzed for the late follow-up period in total and in 2-yr intervals. Outcomes up to age 20 were included. Two-sided Fisher exact and t-tests were used appropriately. There were 264 subjects (256 SS; 54.9% male). Mean age at first visit was 4.1±2.3 mos (±S.D.) and mean follow-up was 12.1±4.3 yrs. The following early hospitalizations occurred: 53 subjects (20.1%) had pain crisis; 16 (6.1%) had dactylitis, and 85 (32.9%) had ACS. There were 5 deaths and 30 overt strokes. Sixty-six subjects were treated with HU (37), CT (40), and/or SCT (1). We found that subjects who had early pain, dactylitis, or ACS (compared with those who did not) were not more likely to die (1.7 vs. 2.1%; P&gt;0.99) or have a stroke (12.2 vs. 10.3%; P=0.69). However, the use of a disease-modifying therapy was more common among subjects who had early pain (37.7 vs. 19.9%; P=0.01) and ACS (37.6 vs. 16.2%; P&lt;0.001), but not dactylitis (18.8 vs. 23.6%; P&gt;0.99). This prediction held only for HU use when the treatments (HU, CT, or SCT) were analyzed separately. Subjects who experienced early pain or ACS had on average a 2.2-fold (P=0.02) or 2.1-fold (P=0.01), respectively, higher number of late pain crises between ages 3 and 11, but not beyond (all P&gt;0.05). Dactylitis did not predict a higher number of late painful events at any age (all P&gt;0.05). Likewise, neither early pain nor dactylitis was associated with a higher number of hospitalizations for late ACS (all P&gt;0.05). However, subjects who had early ACS had a 1.7 to 3.6-fold higher mean number of ACS events throughout all late age groups (all P&lt;0.05). In summary, early hospitalization for pain, dactylitis, or ACS did not predict death or stroke. Early pain and ACS were associated with use of HU in later childhood, but not CT or SCT. Early pain and ACS predicted an increased number of hospitalizations for pain until age 11, but not beyond. Early ACS was a strong predictor of recurrent ACS throughout childhood. Notably, we found that hospitalization for dactylitis had no particular prognostic significance, unlike the CSSCD. In conclusion, the prognostic significance of early vaso-occlusive complications is limited.

scholarly journals Longitudinal effect of disease-modifying therapy on tricuspid regurgitant velocity in children with sickle cell anemia

2021 ◽  
Vol 5 (1) ◽  
pp. 89-98
Author(s):  
Parul Rai ◽  
Vijaya M. Joshi ◽  
Jason F. Goldberg ◽  
Amber M. Yates ◽  
Victoria I. Okhomina ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Entire Cohort ◽  
Disease Modifying Therapy ◽  
Disease Modifying Therapies ◽  
Single Center Study ◽  
Adults And Children ◽  
Disease Modifying ◽  
Hydroxyurea Therapy ◽  
Observation Period

Abstract Elevated tricuspid regurgitant velocity (TRV) ≥2.5 m/s is a predictor of disease severity in adults and children with sickle cell anemia (SCA), but how disease-modifying therapies (DMTs) affect this biomarker is incompletely understood. We investigated the effect of DMTs on TRV elevation in children. In a prospective single-center study, 204 subjects with HbSS or HbSβ0 thalassemia (mean age, 10.6 years; range, 5-18) had echocardiograms with assessment of TRV, with repeat evaluations after 2 years of observation. One-hundred and twelve participants received DMTs (hydroxyurea, n = 72; monthly erythrocyte transfusions, n = 40), 58 did not receive any DMT, and 34 were begun on hydroxyurea during this observation period. In the entire cohort, an increase in hemoglobin of 1.0 g/dL was associated with a 0.03-m/s decrease in TRV (P = .024), and a decrease in absolute reticulocyte count of 1.0 × 106/mL was associated with a 0.34-m/s decrease in TRV (P = .034). Compared with baseline, hydroxyurea exposure (continuous or newly started) was associated with an average 5% decline in mean TRV at the 2-year evaluation. Among participants newly started on hydroxyurea (mean treatment duration 1.2 ± 0.6 years), an increase in hemoglobin of 1.0 g/dL was associated with a 0.06-m/s decrease in TRV (P = .05). We conclude that hydroxyurea therapy may mitigate TRV elevation in children with SCA, possibly as a result of a reduction in hemolysis and improvement in anemia.

scholarly journals Increased Hydroxyurea Prescribing Practices over Ten Years with Improved Clinical Outcomes in Children with Sickle Cell Anemia: A Single Center's Experience

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-34
Author(s):  
Kristine Anne Karkoska ◽  
Kevin E Todd ◽  
Kelly Clapp ◽  
Lynette Fenchel ◽  
Theodosia A. Kalfa ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Research Funding ◽  
Group Versus ◽  
First Year ◽  
Prescribing Practices ◽  
Clinical Complications ◽  
Disease Modifying Therapy ◽  
Disease Modifying ◽  
First Year Of Life

Introduction: Sickle cell anemia (SCA) is a severe and life-threatening disorder that requires treatment to prevent short- and long-term complications and prolong life. The primary disease-modifying therapy for SCA remains hydroxyurea (HU). Due to 30 years of evidence demonstrating safety and efficacy culminating with BABY HUG, the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines recommended offering HU to all children with the severe sickle cell genotypes (HbSS, HbS-0thalassemia) beginning at 9 months of age. Despite these recommendations, HU utilization in pediatric patients in the US remains with rates reported as low as 38-47% among the most severe genotypes as recently as 2017. Providers have identified a number of barriers to more widespread use, including the inability to identify which patients may benefit, concern for possible side effects, uncertainties regarding dose, and concerns regarding possible nonadherence. As complications begin as early as the first year of life, it is a disservice to withhold a proven therapy. Here, we describe the effective and nearly universal uptake of HU in our pediatric SCA population at Cincinnati Children's Hospital Medical Center (CCHMC). Methods: We performed an IRB-approved retrospective review to assess the hydroxyurea prescribing practices and clinical complications of patients with SCA treated at CCHMC from 2010-2019. Following the NHLBI guidelines' release in 2014, we changed the recommended age of HU initiation to be within the first year of life. Corresponding with this change, we have initiated HU for most young children with an individualized, pharmacokinetics (PK)-guided dosing strategy through both the Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT03789591) and the Hydroxyurea Optimization through Precision Study (HOPS, NCT03789591). Due to the onset of symptoms for some patients before 9 months, we have offered HU initiation as early as 6 months of age since 2015. Our objective was to compare the rates of HU utilization, age of initiation, and hospitalization rate before (2010-13) and after (2014-19) the release of the NHLBI guidelines and the start of the TREAT study in 2014. Demographic and clinical data, including sickle cell genotype, prior/alternative therapy, SCA-related complications, HU dosing, and laboratory values were abstracted from each patient's electronic medical record (EMR). Patients were identified using the EMR's sickle cell registry. Results: We identified 439 patients with sickle cell disease followed at CCHMC from 2010-2019 (47% female, age range: 0-22 years); 275 had SCA (HbSS, HbS-0-thalassemia, or HbSD). The proportion of patients with SCA prescribed HU increased from 2010-19, from 35% in 2010 to 80% in 2019 with significantly more patients initiating HU during 2014-19 versus 2010-13 (average 20 versus 12 patients/yr, p = 0.0028, Figure 1A). The age of HU initiation was significantly lower during 2014-19 compared to 2010-13 (median = 2 y vs 6 y, p = 0.00028). Of 35 patients with SCA not on HU in 2019, 28 received chronic transfusions and the remaining 7 received no disease-modifying therapy with 3/7 patients not yet at the age to start HU. Ninety-six percent (53/55) of children with SCA born during 2014-19 were on treatment, including 52 on HU (median starting age = 10 months) and 1 on chronic transfusions; 45/52 (87%) were enrolled on TREAT or HOPS. With increased HU utilization during this study period, the number of admissions for sickle-related events was significantly lower in the 2014-19 group versus 2010-13 (2.8 vs 6.9 admissions/pt, p = 9.0 x 10-10) with no change in non-SCA related admissions, most commonly for fever (3.8 vs 4.0 admissions/pt, p = 0.8, Figure 1B). Conclusions: HU has become the standard of care for children with SCA, beginning at 6-9 months of age, prior to the onset of acute and chronic complications. Despite widespread concerns that HU will not be accepted by patients and national trends demonstrating low rates of utilization, we have shown that a deliberate, systematic, and preventive approach to HU is possible and results in nearly universal acceptance of HU for young patients with SCA. This has translated to excellent laboratory responses and significantly fewer SCA-related clinical complications in our population. Our approach and improved patient outcomes can serve as a model for other programs to expand their HU treatment for more children with SCA. Figure 1 Disclosures Kalfa: Agios Pharmaceuticals, Inc: Consultancy, Research Funding; Forma Therapeutics, Inc: Research Funding. Malik:Aruvant Sciences, CSL Behring: Patents & Royalties; Aruvant Sciences, Forma Therapeutics, Inc.: Consultancy.

TERATOGENIK EKSTRAK ETANOL UWI BANGGAI UNGU (Dioscorea alata L.) PADA MENCIT BETINA (Mus musculus)

2020 ◽  
Vol 5 (2) ◽  
pp. 309-318
Author(s):  
Ihwan Ihwan ◽  
◽  
Rahmatia Rahmatia ◽  
Khildah Khaerati ◽  
Keyword(s):  
Treatment Group ◽  
Embryo Development ◽  
Mus Musculus ◽  
Birth Defect ◽  
Abnormal Development ◽  
Dioscorea Alata ◽  
Treatment Groups ◽  
Study Results ◽  
Pregnant Mice ◽  
Ethanol Extracts

Teratogenic is an abnormal development on embryo and is the cause of congenital defect or birth defect. This study aims to determine the effect of the addition of Dioscorea alata L. ethanol extracts to the embryo development on pregnant mice whose given orally to 24 mice which divided to 4 treatment groups, they are the normal group (NG) with NaCMC 0.5%; 28 mg/KgBB treatment group; 35 mg/KgBB; 42 mg/Kg BB. The addition of Dioscorea alata L ethanol extracts was done on the sixth day until the 15th day of pregnancy. On the 18th day of pregnancy, Laparaktomi was done to the pregnant mice and the embryo was taken out of the uterus. The observation was done to the fetus numbers, weight weighing of the fetus's body, dan length measurement of the fetus's body. Another observation is the observation of the external organ defect of the embryo. The study results that the addition of Dioscorea alata L ethanol extracts with various doses have no significant effect (P>0.5) to the mice external fetus development. On the examination of the fetus, we can conclude that Dioscorea alata L ethanol extracts don’t give any effect that may cause the defect of the fetus’ external organ.

scholarly journals Assessment of Bone Marrow Function in Sickle Cell Anaemia Patients Using Corrected Reticulocyte Counts

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4581-4581
Author(s):  
Titilola S. Akingbola ◽  
Chinedu Anthony Ezekekwu ◽  
Joseph Yaria ◽  
Santosh L. Saraf ◽  
Lewis L. Hsu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
P Value ◽  
Production Index ◽  
Risk Of Death ◽  
Increased Risk ◽  
Reticulocyte Production

Abstract Introduction: Chronic hemolysis occurs in sickle cell anemia as a result of recurrent sickling and other abnormalities of the red blood cells including eryptosis. Exuberant reticulocytosis is anticipated to partially compensate for the resultant anemia. Sickle cell anemia patients may also have aplastic crisis, bone marrow (BM) infarction and erythropoietin deficiency which could lead to reticulocytopenia despite the anemia. High degree of reticulocytosis among asymptomatic infants with sickle cell anemia has been associated with an increased risk of death or stroke during childhood. Assessment of BM function in sickle cell anemia is important due to potential complications associated with both under-activity and hyperactivity. This study aimed at evaluating the erythropoietic function of the BM in steady state sickle cell anemia using corrected reticulocyte counts. Methods: This study was carried out at the hematology clinic in the University College Hospital, Ibadan. HbSS patients in steady state were recruited from the hematology clinic. Local ethical committee approval was obtained and all participants gave written informed consent. Patients with M. tuberculosis, Hepatitis B, HIV and P. falciparum infection were excluded. Peripheral blood samples were analyzed using Sysmex Ki-X21 for complete blood count (CBC) and standard point of care for serum electrolytes and liver function tests. The glomerular filtration rates were calculated using the Cockcroft-Gault formula. Reticulocyte counts were determined manually using fresh samples from K2 EDTA bottles and methylene blue stain. Two drops of stain were mixed with two to four volumes of anticoagulated blood and incubated at 37ºC for 15 minutes. Afterwards, the cells were re-suspended and blood films were made. Corrected reticulocyte count and reticulocyte production index were calculated. Participants were categorized according to corrected reticulocyte counts of greater than or less than 2.5%. Univariate and multivariate analyses were performed to determine variables associated with corrected reticulocyte count <2.5%. Results: 92 HbSS patients were recruited with a mean (SD) age of 19.6 (5.8) years. There was no correlation between age and eGFR (p-value: 0.227). Median (range) reticulocyte count, corrected reticulocyte count and reticulocyte production index were 5.5 (0.5 - 29.9), 3.3 (0.1 - 17.1) and 1.7 (0.2 - 8.6) respectively. 40 (43.5%) patients had corrected reticulocyte count <2.5% and 52 (56.5%) had a corrected count >2.5%. Those corrected reticulocyte count <2.5% were older (p: 0.013), taller (p: 0.041) and had higher aspartate transaminase (AST) levels (p: 0.006) than those with corrected counts >2.5% (Table 1). CBC parameters were not different when compared between both groups. Results of multivariate logistic regression analysis carried out showed that only AST was independently linked with corrected reticulocyte count <2.5% (R2: 0.172, p-value: 0.001) (Table 2). Table 1. Factors Associated with Low Reticulocyte Count Corrected count<2.5% Corrected count>2.5% p-Value Age (Mean, SD) 21.4 (6.3) 18.4 (5.0) 0.013 Gender (N, %) Male 22 (55.0) 28 (53.8) 0.912 Female 18 (45.0) 24 (46.2) Height (Mean, SD) 1.6 (0.1) 1.5 (0.1) 0.041 BMI (Mean, SD) 18.7 (3.1) 18.7 (3.0) 0.753 GFR (Mean, SD) 64.3 (37.7) 66.4 (29.3) 0.453 Bilirubin (Mean, SD) 1.7 (1.1) 1.9 (2.6) 0.674 AST (Mean, SD) 22.5 (13.5) 14.5 (6.6) 0.006 ALT (Mean, SD) 13.4 (7.7) 14.4 (11.1) 0.876 Table 2. Independent Predictors of Corrected Reticulocyte Count <2.5% or 95% CI p-Value Age 1.08 0.97 - 1.21 0.169 Height 19.8 0.11 - 366.10 0.259 AST 1.10 1.04 - 1.17 0.002 Hemoglobin 1.00 0.97 - 1.02 0.872 R2: 0.172, p: 0.001 Conclusion: Despite corrected reticulocyte count <2.5% in about half of the patients, there were similar hematological parameters and eGFR in both groups of patients. AST is a marker of hemolysis and low ALT rules out hepatic involvement. Since only 17.2% of the variability in BM response as assessed by corrected reticulocyte count could be accounted for by variables included in this study, there is a need to further evaluate the BM function of sickle cell patients to establish the causes of corrected reticulocyte count <2.5% in the setting of anemia, having ruled out erythropoietin as well as iron, folate or cobalamin deficiencies. This will aid the development of a functional algorithm for the individualized management of sickle cell disease patients with anemia. Disclosures No relevant conflicts of interest to declare.

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