Targeted Education after an Emergency Department Visit Increases Hydroxyurea Initiation in Children with Sickle Cell Anemia

Abstract Introduction: Hydroxyurea decreases many complications of sickle cell anemia (SCA) but is underused in treatment-eligible patients. Barriers to hydroxyurea initiation occur on the health care system, provider, and patient level. Novel strategies to increase hydroxyurea use in patients with SCA are needed. To address this challenge at our center, we implemented the Quick Start Hydroxyurea Initiation Project (Q-SHIP). Methods: Patients with SCA were eligible to participate in Q-SHIP if they presented to the Children's National Health System (CNHS) emergency department (ED) for pain or acute chest syndrome and were not taking hydroxyurea. Patients <9 months old, on chronic transfusions, pregnant, or not followed by CNHS hematology were excluded. Eligible patients were referred to a weekly Q-SHIP clinic visit focused on hydroxyurea education and were offered initiating treatment at the visit's conclusion. Participants completed a pre-session questionnaire, discussed hydroxyurea with a hematologist using a handbook developed by CNHS, and watched videos featuring patients and parents of children with SCA sharing their experience with hydroxyurea. Subjects were classified as starting hydroxyurea if they had a clinic visit for hydroxyurea monitoring within 3 months of participation in a Q-SHIP session. Results: Over 13 months (2/1/2016 - 3/31/2017) 65 eligible patients participated in Q-SHIP a median of 5 days (IQR 2, 20 days) after ED or hospital discharge. Although 44% (28/64) of participants reported no previous hydroxyurea offer, provider clinic documentation indicated that 61% (17/28) of these families had declined a previous hydroxyurea offer. After Q-SHIP, 55% (36/65) of participants started hydroxyurea. Subjects who started hydroxyurea after Q-SHIP were similar to those who did not, except subjects who started were more likely have a history of an intensive care unit admission (Table 1). After a median follow-up of 11 months, 81% (29/36) of participants who started hydroxyurea after Q-SHIP continued on therapy. Among Q-SHIP participants continuing treatment, mean corpuscular volume increased by a median of 8.6 fL (IQR +5.4, +17.7, p<0.0001) and hemoglobin F increased by a median of 5.8% (IQR +3.0, +11.3, p<0.001). One year after implementation of Q-SHIP, the proportion of treatment-eligible patients with SCA who presented to the ED with pain or ACS who were receiving hydroxyurea increased; February 2016: 56% (32/57) vs. February 2017: 73% (43/59), p=0.059. Conclusion: Addressing indications for hydroxyurea therapy in a clinic encounter exclusively for this purpose soon after a SCA complication is a meaningful time to meet with families of children with SCA to initiate treatment. Disclosures No relevant conflicts of interest to declare.

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Transcranial Doppler Screening Adherence Among Children with Sickle Cell Anemia Seen in the Emergency Department

Blood ◽

10.1182/blood-2018-99-115057 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3569-3569

Author(s):

Julie K. Weisman ◽

Carrie Diamond ◽

Sarah Kappa ◽

Robert Sheppard Nickel

Keyword(s):

Emergency Department ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Transcranial Doppler ◽

Clinic Visit ◽

Cell Disease ◽

Screening Guidelines ◽

History Of ◽

Screening Adherence

Abstract Background: Annual transcranial doppler (TCD) screening is strongly recommended for patients with sickle cell anemia (SCA) between the ages of 2 to 16 years to identify children at highest risk for stroke. Implementation of this screening and treating identified patients with chronic transfusion has decreased the incidence of overt stroke. Nonetheless, adherence to TCD screening guidelines is poor and many children with SCA do not receive an annual TCD. The purpose of this study is to evaluate adherence to TCD screening among a cohort of patients with SCA seen in the emergency department (ED) for an acute problem. Previous work has demonstrated that SCD-related outpatient visits are important "missed opportunities" for TCD screening. We hypothesized that ED encounters also represent potential opportunities to identify patients in need of TCD screening who do not attend clinic regularly. Methods: We conducted a retrospective chart review of the medical records of all patients with sickle cell disease (SCD) seen in the ED at a large, urban pediatric institution between February 2016 and April 2017. Patients were identified using an ED clinical registry that includes all ED patient encounters. We excluded patients who do not need TCD screening (sickle cell disease genotypes other than SS and Sβ0 thalassemia, age <2 or >16 years, on chronic transfusions, history of hematopoietic stem cell transplant). We also excluded patients documented to previously have inadequate TCD bone windows and patients who did not receive their regular hematology care at the study institution. For eligible patients who had multiple ED encounters during the study period, data was extracted at the time of the first ED encounter during the study period. Eligible patients who had received a TCD in the last year (adherent to TCD screening) were compared to patients who had not received a TCD in the last year (nonadherent to TCD screening). Categorical data was analyzed with the chi-square test. Continuous data was analyzed using the two-sample t-test. P value of <0.05 was considered statistically significant. Results: During the 64 week study period, 739 patients with SCD were seen in the ED. A total of 482 patients were excluded for the following reasons: non-SCA genotype (n=164), age (n=139), followed at outside institution (n=129), chronic transfusion (n=38), prior TCD window problem (n=10), history of transplant (n=2); leaving 257 patients with SCA aged 2-16 years for study. Among this study group, 63 patients (25%) had not received a needed TCD in the last year, including 19 patients (7%) who had never had a TCD. When excluding patients aged 2-2.99 years (n=33) in whom a first TCD may have been planned soon after the ED encounter, a similar proportion of patients still had not received a TCD in the last year (53/224, 24%) but a slightly smaller proportion had never had a TCD (9/224, 4%). Patient age and sex were not associated with TCD screening adherence (p>0.7). Patients adherent to TCD screening were more likely to be taking hydroxyurea (67% vs. 29%, p<0.0001). A recent hematology clinic visit was significantly associated with TCD screening adherence. All patients adherent to TCD screening had a clinic visit in the last year compared to 75% of nonadherent patients, p<0.0001. The mean interval time since the last hematology clinic appointment from the ED encounter was greater for TCD nonadherent patients, 70 vs. 270 days p<0.0001 (Figure). Conclusion: Patients with SCA who present to the ED and are nonadherent to TCD screening guidelines are less likely to have had a recent hematology clinic visit. Therefore, the ED may be an important location for identifying patients lost to regular clinic follow-up in need of a TCD. An intervention that specifically targets this patient population will likely improve TCD screening rates and stroke prevention. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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PADI4 Gene Polymorphism As a Risk Factor for Acute Chest Syndrome in Sickle Cell Anemia Patients

Blood ◽

10.1182/blood.v130.suppl_1.954.954 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 954-954 ◽

Cited By ~ 1

Author(s):

Francine Chenou ◽

Bidossessi Wilfried Hounkpe ◽

Dulcinéia Martins de Albuquerque ◽

Igor de Farias Domingos ◽

Aderson da Silva Araujo ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Gene Polymorphisms ◽

Conflicts Of Interest ◽

Inflammatory Diseases ◽

Clinical Manifestations ◽

Chronic Inflammatory Disease ◽

Acute Chest Syndrome ◽

Cycle Sequencing ◽

History Of

Abstract Introduction: Sickle cell anemia (SCA) is a chronic inflammatory disease with heterogeneous clinical features and the reasons for the heterogeneity of the clinical manifestations has not been fully elucidated. New mediators of the pathogenesis of SCA described recently include the formation of Neutrophil Extracellular Traps (NETs), which may contribute to the amplification of inflammation via the production of pro-inflammatory mediators. Peptidylarginine Deiminase 4 (PADI4) is a critical regulator of NETosis by mediating histone citrullination, an essential step for the generation of NETs. There appears to be a relationship between PADI4 gene polymorphisms and the pathophysiology of other inflammatory diseases in which NETosis seems to be relevant. Our aim was to investigate the association of PADI4 gene polymorphisms [rs874881(G>C), rs1748033(T>C), rs11203366(G>A), rs11203367 (T >C), rs2240340 (T>C)], which have been previously associated with increased PADI4 mRNA stability and with some clinical manifestations in cohorts of SCA patients. Methods: The study included 194 SCA patients (93 males and 101 females with mean age 33.29 ± 9.54 years) being followed up at the Hematology and Hemotherapy Foundation of Pernambuco (HEMOPE), Recife, Brazil. PADI4 gene polymorphisms were performed by Polymerase Chain Reaction (PCR) and their products were sequenced using the Big Dye Terminator Cycle Sequencing Ready Reaction Kit v3.1 (Applied Biosystems, CA, USA). These results obtained were compared with the clinical data obtained from the patients' records. Ethical approval was obtained from Ethics Committee of HEMOPE and all patients gave informed consent. Results: The frequencies of the genotypes found were as follows: rs874881 (22.2% GG, 50.5% GC, 27.3% CC); rs1748033 (17% TT, 42.3% TC, 40.7% CC); rs11203366 (21.1% GG, 50% GA, 28.9% AA); rs11203367 (20.6% TT, 49.5% TC, 29.9% CC); rs2240340 (24.7% TT, 46.4% TC, 28.9% CC). The distribution of the genotypes was in accordance with the Hardy-Weinberg equilibrium (p > 0.05). Twenty-four patients (12.4%) presented with a history of acute chest syndrome (ACS), 27 (13.9%) with stroke, 168 (86.6%) with vaso-occlusive crisis (VOC), and 81 (47.8%) with leg ulcers (LU). No association was observed between the polymorphisms studied and the history of LU, VOC and stroke in the patients (p > 0.05). However, for rs 874881 and 1748033 with the G and T alleles, respectively, were associated with a higher risk of ACS (OR: 2.96, p = 0.02 and OR: 4.75, p = 0.01, respectively). Conclusion: In the present study, we found an association between the wild type alleles (rs874881G and rs1748033T) and a history of ACS in our cohort of SCA patients. There is need for future studies on these polymorphisms in larger cohorts of SCA patients to affirm this association. Disclosures No relevant conflicts of interest to declare.

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Correlation of Iron Levels with Asthma and Lung Function in Pediatric Patients with Sickle Cell Anemia

Blood ◽

10.1182/blood-2020-136661 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 12-12

Author(s):

Yusra D Shaikh ◽

Nataly Apollonsky ◽

Bruce Bernstein

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Serum Iron ◽

Pediatric Patients ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

Iron Level ◽

Obstructive Sleep ◽

History Of ◽

Hb S

Introduction:Significant morbidity and mortality in patients with sickle cell disease (SCD) is attributed to the pulmonary sequalae of the disease. Patients with SCD often suffer airway hyper-reactivity, acute chest syndrome (ACS), chronic lung disease, pulmonary hypertension (PHTN), and obstructive sleep apnea (OSA). Recent literature has provided evidence supporting the strong association between asthma and airway hyper-reactivity in SCD. One of the factors linked to chronic inflammation and asthma is iron status. The present study examined whether iron levels are associated with pulmonary complications in pediatric patients with SCD. Method:Through retrospective review of electronic medical records (EMR) we evaluated patients with diagnosis of asthma and SCD. All patients with available PFT (3/21/2013-3/11/2020) and iron studies were included in the analysis. Chi square and ANOVA tests were used to explore relationships of respiratory conditions with lab data and relevant medical history. Results:The analysis reviewed information of 100 patients with SCD -- 56 males and 44 females The sample population had the following genotypes: 63% Hemoglobin (Hb) SS, 23% Hb SC, 2% Hb S Beta Zero Thalassemia, and 12% Hb S Beta Thalassemia. 38% of these patients were receiving treatment via hydroxyurea. The results generated found that patients with a large airway obstruction (LAO) had a marginally statistically significantly higher serum iron level than those with no LAO (p=0.067.) Patients with homozygous Hb S disease were four times as likely to have a history of ACS (p=0.004) than those without and were marginally significantly more likely to be SS and SB0Thal (p=0.052). Patients with history of ACS had a significantly higher mean iron saturation and lower total iron binding capacity (TIBC.) Patients with PHTN had significantly higher serum iron levels (p=0.029). Conclusion:Our findings reveal that while iron might play a more significant role in the development of PHTN and ACS in patients with SCD, the role in asthma is borderline in our sample. These findings, although of borderline statistical significance p=0.067, are clinically noteworthy. These results may open a new window for therapy targeted at maintaining iron in normal physiologic ranges to decrease pulmonary complications in patients with sickle cell anemia. Further studies with larger samples are necessary to clarify the meaning of our marginally significant findings. Disclosures No relevant conflicts of interest to declare.

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Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.

Blood ◽

10.1182/blood.v104.11.3759.3759 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3759-3759

Author(s):

Onyinye C. Onyekwere ◽

Andrew Campbell ◽

James Williams ◽

Peter Gaskin ◽

Sohail Rana ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Artery ◽

Sickle Cell ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

University Of Michigan ◽

Cell Disease ◽

Hemoglobin F ◽

Howard University ◽

History Of

Abstract Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table. Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD. Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3

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Elevated Systolic Blood Pressure and Low Fetal Hemoglobin Are Risk Factors for Silent Cerebral Infarcts in Children with Sickle Cell Anemia.

Blood ◽

10.1182/blood.v114.22.262.262 ◽

2009 ◽

Vol 114 (22) ◽

pp. 262-262

Author(s):

Sharada A. Sarnaik ◽

James F. Casella ◽

Bruce A Barton ◽

Michele Afif ◽

Gladstone Airewele ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Systolic Blood Pressure ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Beta Thalassemia ◽

Cerebral Infarcts ◽

Hemoglobin F ◽

Elevated Systolic Blood Pressure

Abstract Abstract 262 Introduction: The most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and Methods: In this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta° thalassemia and no history of overt strokes or seizure were evaluated. Results: A total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. Conclusion: SBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. Disclosures: No relevant conflicts of interest to declare.

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Serum Transferrin: An Independent Predictor of Mortality in Sickle Cell Anemia

Blood ◽

10.1182/blood.v118.21.2126.2126 ◽

2011 ◽

Vol 118 (21) ◽

pp. 2126-2126

Author(s):

Zahra Pakbaz ◽

Mariana E Hildesheim ◽

Shoaib Alam ◽

Darlene Allen ◽

Caterina Minniti ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Sickle Cell ◽

Serum Ferritin ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Independent Predictor ◽

Stable Condition ◽

Acute Chest Syndrome ◽

Serum Transferrin ◽

Significant Difference

Abstract Abstract 2126 Introduction: Serum ferritin (SF), the most convenient marker of iron burden in sickle cell anemia (SCA), is potentially confounded by effects of inflammation in SCA. Serum transferrin (STF) has been described as one of the independent predictors of elevated tricuspid regurgitant velocity (TRV) in SCA. Therefore in this report we investigate the potential predictive role of STF in morbidity and mortality of individuals with SCA. Methods: Patients with sickle cell disease documented by high-pressure liquid chromatography were eligible for the study. Four hundred and sixty SCA patients were recruited in this study from the community through multimedia advertisements, community outreach, and regional clinics. All evaluated patients were screened by history taking, physical examination, laboratory studies, and transthoracic echocardiography. All patients provided written informed consent. The advertisements and protocol were approved by the institutional review boards of the National Heart, Lung, and Blood Institute and Howard University. Only outpatients in stable condition were included; patients who had had a vaso-occlusive crisis within the previous two weeks or an episode of acute chest syndrome within the previous four weeks were excluded. Results: Two hundred and sixty two participants with HbSS were included in the data analysis. Forty-seven percent were male. Median age was 32 years old. Median TRV in this cohort was 2.4 m/s. Forty nine percent of participants had TRV≥2.5 m/s and 19% had TRV≥3 m/s. Patients with lower STF (<164 mg/dl) were older (p=0.01), had more blood transfusions in the past (p<0.0001) and did not have more complications of sickle disease (priapism, acute chest syndrome, leg ulcers or emergency room visits, all p>0.05), but all-cause death rate was higher (22% vs. 6%, p=0.0001). Hemoglobin, CRP, alkaline phosphatase, uric acid, placenta growth factor (<0.001), SF and iron saturation were found to be higher and kidney function was worse. Patients with lower STF level were also more likely to have TRV≥3.0 m/s (32% vs. 13%, p<0. 001) but there was no significant difference in BNP and ejection fraction. Patients with lower STF had endothelial dysfunction, as indicated by a blunted forearm blood flow (FBF) response to infusion of acetylcholine into the brachial artery (p<0.01). Among age, gender, BNP, TRV,GFR,WBC, STF, systolic blood pressure and fetal hemoglobin, the Cox proportional analysis of mortality found TRV, GFR and STF the independent significant predictors of mortality in this cohort. Kaplan-Meier survival curve showed that patients with transferrin <164 mg/dl had significantly lower survival (p<0.001). Conclusion: In this cohort of adults with sickle cells anemia, STF is found to be an independent predictor of endothelial dysfunction, high TRV and mortality. It may be a more sensitive predictor than serum ferritin. We propose that iron overload may induce a state of endothelial dysfunction that is a risk factor for clinical vasculopathy and death. Disclosures: No relevant conflicts of interest to declare.

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Hematologic Effects of Hydroxyurea Treatment in Children with Hb SC and SB+ Thalassemia

Blood ◽

10.1182/blood.v124.21.4077.4077 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4077-4077

Author(s):

Rakeshkumar J Patel ◽

Jeffrey D. Lebensburger ◽

Christina J. Bemrich-Stolz ◽

Thomas H. Howard ◽

Lee Hilliard

Keyword(s):

Conflicts Of Interest ◽

Fetal Hemoglobin ◽

Acute Chest Syndrome ◽

Compound Heterozygous ◽

Average Dose ◽

Hemoglobin F ◽

Viscosity Increase ◽

Hydroxyurea Treatment ◽

In Parenthesis ◽

One Year

Abstract Background: The effects of hydroxyurea in clinically severe hemoglobin SC (Hb SC) and hemoglobin Sβ+ thalassemia patients (Hb Sβ+) are not well defined. The largest previous report reviewed 15 children with Hb SC treated with hydroxyurea (Yates, et al: Pediatr Blood Cancer 2013;60: 323-325). Prior studies describe a mixed hematologic pattern of response, but all pediatric reports show an increase in fetal hemoglobin and MCV in Hb SC. To further evaluate the hematologic effect of hydroxyurea in these compound heterozygous conditions, we reviewed 27 patients with Hb SC and 7 with Hb Sβ+ treated to date at our institution Methods: The medical records of all children treated at least a year with hydroxyurea for clinically severe Hb SC and Hb Sβ+ were reviewed. Age at start and indication for hydroxyurea were documented. Laboratory values were recorded at hydroxyurea start and at the visit that fell closest to one year of therapy. Data collected included hemoglobin (Hb), hematocrit (Hct), mean corpuscular volume (MCV), white blood cell count (WBC), absolute neutrophil count (ANC), platelet count (PLT), absolute reticulocyte count (ARC), hemoglobin F % (Hb F), lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and total bilirubin. The milligram/kilogram dose of hydroxyurea was recorded at start and at 12 months of treatment. Paired differences were compared at baseline and 12 months of treatment. Results: The average age at hydroxyurea start for patients with Hb SC was 9.4 years + 3.8. Fifteen of the 27 patients were male. Hb Sβ+ patients’ average age at start was 10.7 years + 6.9. Five of the 7 Hb Sβ+ patients were male. Twenty-six of the 27 patients with Hb SC were treated with hydroxyurea for recurrent painful crises and one Hb SC patient started hydroxyurea for recurrent acute chest syndrome. All 7 Hb Sβ+ patients were treated with hydroxyurea due to recurrent painful crises. The average dose of hydroxyurea for Hb SC patients was 22 mg/kg/day and 21mg/kg/day for the Hb Sβ+ group. There was no significant change in mg/kg dose from hydroxyurea start to the 12 month interval. For patients with Hb SC, significant decreases were seen in the following lab values with p values noted in parenthesis: WBC (0.0001), PLT (0.0122), ARC (0.0002) , ANC (0.0002) and AST(0.0408). Significant increases were seen in MCV (0.0003) and Hb F (0.0181). However, Hb F and MCV values in Hb SC patients (average Hb F of 7.4% (+5.8%) and MCV of 87 fl (+14) after 12 months of treatment) were not as high as seen in good hydroxyurea responders with Hb SS disease Hb, Hct and bilirubin did not significantly change in patients with Hb SC. For Hb Sβ+, statistically significant decreases were seen in WBC (0.0157), PLT (0.0476), and ANC (0.0047). MCV also increased in Hb SB+ from 70 fl (+6.63) at baseline to 80 fl (+5.4) at 12 months (p= 0.0054). Hb F did not change in HbSβ+ patients with values of 7% (+ 4.2) at baseline and 9.5% (+ 5) at 12 months (p= 0.4042). Similar to the Hb SC group, Hb and Hct did not significantly increase in the Hb Sβ+ patients. Conclusions: This report of the largest pediatric cohort of Hb SC and Hb Sβ+ patients treated with hydroxyrea to date shows hematologic effect, although with some differences from typical response in patients with Hb SS disease. Most notably, Hb and Hct did not change in either group which is important given concerns about viscosity increase in patients with higher baseline values. Further study in larger numbers of patients is needed to evaluate hematologic effect and clinical outcome. Disclosures No relevant conflicts of interest to declare.

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Effects of Hydroxyurea on Brain Function in Children with Sickle Cell Anemia

10.22541/au.161446690.09460099/v1 ◽

2021 ◽

Author(s):

Winfred Wang ◽

Ping Zou ◽

Scott Hwang ◽

Guolian Kang ◽

Juan Ding ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Brain Function ◽

Visual Stimulation ◽

Brain Mri ◽

Bold Signal ◽

Hemoglobin F ◽

Neurocognitive Dysfunction ◽

Mean Values ◽

One Year

Introduction: Sickle cell anemia (SCA) results in numerous adverse effects on the brain, including ischemic lesions and neurocognitive dysfunction. Hydroxyurea has been utilized extensively for management of SCA, but its effects on brain function have not been established. Methods: We examined prospectively the effects of one year of treatment with hydroxyurea on brain function in a cohort of children with SCA (HbSS/HbSβ0-thalassemia) by baseline and exit evaluations, including comprehensive neurocognitive testing, transcranial Doppler ultrasound (TCD), and brain MRI [silent cerebral infarcts (SCI), gray matter cerebral blood flow (GM-CBF), and blood oxygen level dependent (BOLD) signal from visual stimulation]. Results: Nineteen patients with SCA, mean age 12.4 years (range 7.2-17.8), were evaluated. At baseline, subjects had these mean values: full scale IQ (FSIQ) 81.9, TCD velocity 133 cm/sec, GM-CBF 64.4 ml/100g/min, BOLD signal 2.34% increase, and frequency of SCI 47%. After one year of hydroxyurea, there were significant increases in FSIQ (+2.8, p=0.036) and reading comprehension (+4.8, p=0.016), a significant decrease in TCD velocity (-11.4 cm/sec, p=0.007), and no significant changes in GM-CBF, BOLD, or SCI frequency. Furthermore, FSIQ was associated with higher hemoglobin F (HbF) and lower GM-CBF, but not with hemoglobin level. Discussion: Significant improvement of neurocognition and decreased TCD velocity following one year of treatment support the use of hydroxyurea for improving neurocognitive outcomes in SCA. Understanding the mechanisms of benefit, as indicated by relationships of neurocognitive function with HbF, hemoglobin, and CBF, requires further evaluation.

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Association of MBL2 polymorphism with Leg Ulcers Development in Sickle Cell Anemia Patients

Blood ◽

10.1182/blood.v124.21.4912.4912 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4912-4912

Author(s):

Marcos André Cavalcanti Bezerra ◽

Isabela Cristina Farias ◽

Diego Arruda Falcão ◽

Igor de Farias Domingos ◽

Luana Laranjeira Prado ◽

...

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Conflicts Of Interest ◽

Clinical Manifestations ◽

Monogenic Disease ◽

Prior History ◽

Leg Ulcers ◽

Immune Disorder ◽

History Of ◽

Mbl Deficiency

Abstract Leg ulcers are the most common clinical manifestations of sickle cell anemia (SCA), a monogenic disease with huge clinical diversity among patients. They affect 8% to 10% of SCA patients, reaching a percentage greater than 50% in patients residing in tropical areas. These ulcers occur due to vascular occlusion, tissue hypoxia, hemolysis and genetic factors, presenting a slow healing, high recurrence rate and huge susceptibility to infection. Recently, some studies have shown a positive relationship between the complement system and the development of some vascular diseases and injuries such as leg ulcers in non-SCA patients. Mannan-binding lectin (MBL) is an important component of the humoral innate immune system, and MBL possesses several characteristics indicating that it may play an essential role in wound healing; modulating inflammation and contributing to the clearance of microorganisms and apoptotic cells. In a recent study of chronic leg and foot ulcer patients, serum MBL levels were significantly different between wounds of different etiologies, with chronic venous leg ulcers patients having a higher frequency of MBL deficiency. Polymorphisms in the MBL2 are associated with a reduction in the MBL protein serum levels, increasing risk of developing leg ulcers and also the maintenance of these wounds, compromising the integrity of the immune defence and its response to potential invading pathogens. Here, we aimed to determine the frequency of polymorphisms in the promoter region -221 (Y / X) and -550 (H / L) and exon 1 of the MBL2 and assess the clinical impact of these variants in a northeastern Brazilian SCA population who presented leg ulcers. Two-hundred seventy-five unrelated SCA patients were included. According the leg ulcers presence, the total cohort was classified in patients presenting current or prior history of leg ulcers (n=100) and SCA patients above 18 years with no history of leg ulcers (n=175). Molecular analysis was performed by qPCR. Our population was in Hardy-Weinberg equilibrium. The allelic frequency of haplotypes associated with high MBL production (HYA, LYA) was 54.5% for cases and 62.9% in controls. The genotypes related to low MBL production (HYO, LYO) in cases and controls was 27.5% and 18.6%, respectively. The frequency of genotype related to intermediate MBL production (LXA) was 18% in cases and 18.5% in controls. We had no statistically significant results when we analyzed only the polymorphisms (P>0.05). However, the phenotypic analysis between high and low MBL production revealed that patients with leg ulcers have lower MBL protein levels (P=0.019). We focused specifically on a possible role of MBL deficiency on healing complications, based on the facts that MBL deficiency is the most common immune disorder, and that a common causality for prolonged healing of these ulcers is infection or colonization by bacteria. In our study, MBL deficiency appears to increase the risk of developing leg ulcers in SCA patients. Disclosures No relevant conflicts of interest to declare.

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Pulmonary Function in Children with Sickle Cell Anemia Following Treatment with Hydroxyurea.

Blood ◽

10.1182/blood.v112.11.1435.1435 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1435-1435 ◽

Cited By ~ 1

Author(s):

Elizabeth Record ◽

Tamara New ◽

Randall Brown ◽

LeRoy Graham ◽

R. Clark Brown

Keyword(s):

Pulmonary Function ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Pulmonary Function Tests ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

P Value ◽

Chronic Injury ◽

History Of ◽

Abnormal Pulmonary Function

Abstract Background: Pulmonary function is particularly susceptible to acute and chronic injury occurring in patients with sickle cell anemia (SCA). Acute Chest Syndrome (ACS), a common and potentially fatal complication of SCA, can be the cause or the consequence of abnormal pulmonary function (Siddiqui & Ahmed, 2003). Use of hydroxyurea therapy (HU) is increasing for children with recurrent pulmonary complications, following the findings that HU reduces risk of ACS in adults (Charache et al, 1995). How HU may improve pulmonary function in children with SCA is still ill-defined. The purpose of this study was to assess the change observed on serial pulmonary function tests (PFT) for children prescribed HU for abnormal pulmonary function. Methods: Over 240 children with pulmonary complications, such as acute chest syndrome, reactive airway disease, and chronic hypoxia, have been evaluated in the Sickle Cell Pulmonary Clinic at Children’s Healthcare of Atlanta since beginning in July 2000. As part of the Clinic’s standard of care, PFT were routinely attempted on children over the age of 5. A retrospective review of PFT results was done for the children with SCA and prior abnormal PFT. Children were included in the HU cohort (+HU) if repeat PFTs were available following > 3 months on HU therapy and if time on HU did not include frequent RBC transfusions. Children without history of HU therapy (−HU) were selected for comparison. PFTs were performed on a standard plethysmograph. Paired t-test was used to evaluate observed differences. Results: Thirty-one children with prior abnormal PFT had test before and following prescription of HU. Their mean age was 12.6 (range 6–20) years and mean duration of HU was 21 (range 4–47) months at the time of the repeat PFT. Hematologic changes expected on HU occurred for all 31 children. Twenty-four children followed for abnormal PFT had no history of HU (−HU) and matched the +HU group by gender, age (mean 12.3, range 7–19 years), duration followed at time of repeat PFT (mean 19, range 3–66 months; p=0.36), and initial hematologic parameters. Spirometry findings changed for +HU group, and remained stable for −HU group. Mean FVC and FEV1 values improved significantly on HU, when compared to initial (PreHU) PFT and to −HU controls. Conversion to a normal PFT, as interpreted by a pediatric pulmonologist masked to treatment status, occurred in 18 (58%) and 2 (8%) children in the +HU and −HU groups, respectively. Table 1: Serial PFT and hematologic parameters according to HU exposure −HU (n=24) +HU (n=31) Initial Repeat # PreHU Repeat 1 % predicted value for age, sex and height of subject. 2Mean (SD) #No significant changes compared to Initial, p > 0.05. *P value < 0.001 compared to PreHU; ++P value < 0.001 compared to −HU repeat. PFT parameter 1 TLC 88 (13.6)2 85 (11.7) 85 (13.4) 90 (13.5) FVC 78 (9.8) 79 (9.9) 75 (12.6) 90 (13.2)*,++ FEV1 75 (9.6) 74 (12.2) 72 (11.4) 86 (10.2)*,++ FEF 25-75 75 (22) 72 (28.0) 77 (23.4) 79 (26.8) FEV1/FVC (%) 85(6.7) 82 (9.8) 87 (11.8) 86 (11.1) Pulse oximetry (%) 95 (3.1) 96 (2.4) 94 (4.4) 97 (2.8)* WBC (x103/ul) 14 (3.8) 13 (2.9) 13.02 (2.9) 9.0 (2.1) *,++ Hb (g/dl) 8.0 (0.1) 8.0 (0.9) 7.8 (1.1) 9.1 (1.3) *,++ MCV (fl) 84 (9.2) 85 (10.0) 87.3 (8.1) 101.2 (10.1) *,++ HbF (%) 4.3 (1.5) 5.2 (5.2) 6.0 (3.8) 14.0 (7.3) *,++ Conclusions: Serial PFTs showed improved pulmonary function, following initiation of HU therapy in children with prior abnormal PFT. Routine PFT assessments of children prescribed HU may serve as an objective measure of clinical response in children with SCA and pulmonary complications. These results will help in the design of future prospective studies examining the clinical benefits of HU therapy for children at risk for long-term pulmonary complications.

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