Hydroxyurea Treatment of Young Children with Sickle Cell Anemia: Safety and Efficacy of Continued Treatment – the BABY HUG Follow-up Study

Abstract Abstract 7 BABY HUG [Clinical Trials #NCT00006400], an NIH-NICHD sponsored randomized placebo-controlled trial showed that hydroxyurea (HU) administered to 9–18 month old children with sickle cell anemia (SCA) provides substantial clinical benefit. Benefits include a decrease in pain crises, acute chest syndrome events, need for transfusion and hospital admission; hematologic improvement include higher total and fetal hemoglobin concentration, larger red cell size, and lower WBC counts with toxicity limited to transient reduction in absolute neutrophil count (ANC) [Lancet 2011; 377:1663–72]. The parent or guardian of all 176 children who completed at least 18 months of randomized treatment were offered participation in an initial observational BABY HUG Follow-Up Study and 163 (93%) consented to participate. Clinical and laboratory data were collected every 6 months by structured abstraction of the medical record regarding use of clinically prescribed HU (dose escalation recommended), blood counts, clinical imaging, and sickle cell-related events. At the time of enrollment the family did not know their child's randomized study treatment assignment; 133 (82%) initially chose clinical prescription of open-label HU. Acceptance of HU has remained high through 36 months of follow-up; during each 6 month data collection period 68–75% of participants reported having taken HU. Only 2 patients have left the study (due to relocation) and more than 93% of expected data have been collected. Preliminary analyses as of May 2011, including 417 patient years (pt-yrs) of follow up, demonstrate that in comparison to participants not taking HU, children who continue to take HU have statistically lower rates of pain crises requiring emergency department (ED) visits, episodic transfusions, and hospital admissions for any reason, including acute chest syndrome or febrile illness (see table). The substantial decrease in acute chest syndrome episodes is similar to the effect demonstrated with HU use in the randomized BABY HUG trial in younger infants and consistent with published trials detailing the benefit of HU therapy in older children and adults. The decrease in the rate of admission for febrile events in HU-treated patients is also comparable to that in the randomized trial, but the reason for this benefit is uncertain. There was no difference in hospitalization rates for painful events including dactylitis. Two patients in the non-HU group had a stroke. There were no differences between groups in the frequency of a palpable spleen or rate of acute splenic sequestration crises. Through 36 months of follow up children taking HU had persistently higher hemoglobin and MCV, and lower WBC and ANC than those not taking HU. Results of these analyses including growth and development assessments will enhance our understanding of the impact of HU use in children with SCA starting at a very young age. The accruing data from the BABY HUG Follow-Up Study demonstrate a continuation of the substantial benefits of early HU therapy with no discernable additional toxicities. Ongoing follow up of this cohort is essential to fully define these benefits as children grow, and to observe for late toxicity.Event Rate per 100 pt-yrsHUNo HUp valueED visit for Pain Crisis28.853.60.004Episodic Transfusion18.334.00.010Hospital Admission (any cause)74.9133.20.001Acute Chest Syndrome (admission)9.522.30.0001Febrile Illness (admission)30.764.3<.001Pain Crisis (admission)18.630.40.102 Disclosures: Off Label Use: Hydroxyurea is not indicated for treatment of children with sickle cell disease. Use of this medication was for clinical indications and not mandated by this observational study.

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A randomised controlled trial exploring the impact of a dedicated Health and Social Care Professionals team in the Emergency Department on the quality, safety, clinical and cost-effectiveness of care for older adults: Study Protocol

10.21203/rs.2.12207/v2 ◽

2019 ◽

Author(s):

Marica Cassarino ◽

Katie Robinson ◽

Íde O’Shaughnessy ◽

Eimear Smalle ◽

Stephen White ◽

...

Keyword(s):

Older Adults ◽

Cost Effectiveness ◽

Randomised Controlled Trial ◽

Hospital Admissions ◽

Controlled Trial ◽

Health And Social Care ◽

Effectiveness Of Care ◽

Randomised Controlled ◽

The Impact

Abstract Background : Older people are frequent Emergency Department (ED) users who present with complex issues that are linked to poorer health outcomes post-index visit, often have increased ED length of stay and tend to have raised healthcare costs. Encouraging evidence suggests that ED teams involving health and social care professionals (HSCPs) can contribute to enhanced patient flow and improved patient experience by improving care decision-making and thus promoting timely and effective care. However, the evidence supporting the impact of HSCPs teams assessing and intervening with older adults in the ED is limited and identifies important methodological limitations, highlighting the need for more robust and comprehensive investigations of this model of care. This study aims to evaluate the impact of a dedicated ED-based HSCP team on the quality, safety, clinical and cost-effectiveness of care of older adults when compared to usual care. Methods : The study is a single-site randomised controlled trial whereby patients aged ≥65 years who present to the ED of a large Irish hospital will be randomised to the experimental group (ED-based HSCP assessment and intervention) or the control group (usual ED care). The recruitment target is 320 participants. The HSCP team will provide a comprehensive functional assessment as well as interventions to promote a safe discharge for the patient. The primary outcome is ED length of stay (from arrival to discharge). Secondary outcomes include: rates of hospital admissions from the ED, ED re-visits, unplanned hospital admissions and healthcare utilisation at 30-days, four and six-month follow-up; patient functional status and quality of life (at baseline and follow-up); patient satisfaction; costs-effectiveness in terms of costs associated with ED-based HSCP compared to usual care; and perceptions on implementation by ED staff members. Discussion : This is the first randomised controlled trial testing the impact of HSCPs working in teams in the ED on the quality, safety, clinical and cost-effectiveness of care for older patients. The findings of the study will provide important information on the effectiveness of this model of care for future implementation. Trial registration : ClinicalTrials.gov, NCT03739515; registered on 12 th November 2018. Protocol version 1. URL: https://clinicaltrials.gov/ct2/show/NCT03739515

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Stroke in Sickle Cell Anemia After Excellent Response to Hydroxyurea.

Blood ◽

10.1182/blood.v114.22.4622.4622 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4622-4622

Author(s):

Ubaldo Martinez ◽

Samir K. Ballas

Keyword(s):

Atrial Septal Defect ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Septal Defect ◽

Acute Chest Syndrome ◽

Excellent Response ◽

Blood Exchange ◽

Atrial Shunt ◽

The Right

Abstract Abstract 4622 Introduction Strokes occur in about 10% of children with sickle cell anemia (SS) less than 10 years old. These strokes are usually ischemic in nature. Stroke due to SS in adults is less common and is usually hemorrhagic in nature. We wish to report an unusual adult patient with SS and excellent response to HU who developed a stroke that was unrelated to SS. Case Report and Results A 35-year-old female with sickle cell anemia had mitral valve prolapse and migraine headaches presented 2 days after developing abrupt bilateral blurry vision, left facial numbness and weakness of her left leg. Her SS has been complicated by acute chest syndrome, bilateral hip avascular necrosis and frequent painful crises prior to hydroxyurea (HU) therapy. She was enrolled in the multicenter study of hydroxyurea (MSH) in SS and has been on 2500mg of HU per day for the past 13 years. She had an excellent response to HU with no recurrent acute chest syndrome and decreased need for blood transfusion. After starting HU, the frequency of crises requiring hospital admission decreased from 1 admission every 1 to 2 months to less than 1 admission per year except when hydroxyurea was discontinued for pregnancy. Her fetal hemoglobin increased from 6.1 % before HU to a maximum of 45%. Her MCV increased from 96 fl to a maximum of 132 fl and Hb from 8.0 g/dl to 9.8 g/dl Her exam was remarkable for left lower extremity weakness which was more pronounced proximally. All cranial nerves were intact and there was normal sensation bilaterally. CT scan of the brain showed three foci of hypodensity and MRI of the brain showed increased signal on T2, FLAIR and diffusion weighted images within the frontoparietal deep white matter consistent with infarction in the border zone of the middle cerebral artery (MCA)-anterior cerebral artery (ACA). MR angiography of the intracerebral and extracerebral vessels demonstrated focal narrowing of the right MCA at the trifurcation suggesting an embolic cause. Common causes of stroke were ruled out with routine studies. Her hemoglobin electrophoresis after admission but before blood exchange transfusion showed HbS of 55% and HbF of 45%. She underwent exchange transfusion 2 days after admission and was started on chronic blood exchange transfusions with the assumption that she had ischemic stroke due to SS. Initial transthoracic echocardiogram with contrast injection did not show an atrial shunt. Follow-up transesophageal echocardiogram after discharge showed a secundum atrial septal defect with a defect size of 1.4 cm. Right heart catheterization was performed and the pulmonary flow to systemic flow (Qp/Qs) was 1.7:1. An Amplatzer atrial septal defect (ASD) closure device was deployed with transesophageal echocardiographic guidance and a large thrombus was removed from the right atrium. At the patient's request exchange red cell transfusions were discontinued. The patient has continued treatment with hydroxyurea and aspirin. Conclusions Young patients with cryptogenic stroke have a much higher prevalence of atrial shunts and in particular patent foramen ovale than patients with other forms of stroke and therefore a cause-effect association is suggested. Young adults with stroke should be evaluated for common and reversible causes of stroke including paroxysmal emboli. Transesophageal echocardiography is the gold standard for diagnosing atrial shunts. Strokes in patients younger than age 55 are related to paroxysmal emboli and have a risk of recurrence of approximately 30% within one year. High risk features for stroke recurrence with an atrial shunt include hypercoagulable states, large opening and presence of an atrial septal aneurysm. Optimal management of patients with a stroke and an atrial shunt is unknown. Options include surgical closure, percutaneous device closure, anticoagulation and antiplatelet therapy. Patients with sickle cell disease and stroke should receive long term blood transfusions to reduce HbS below 30% if the stroke is felt to be related to sickle cell disease vasculopathy. The patient described with SS had a stroke and had an atrial septal defect that was repaired. The MRI/MRA findings are consistent with paroxysmal emboli. The patient is receiving treatment with hydroxyurea and aspirin having discontinued red cell exchange transfusions and at two years of follow-up has not had a recurrent stroke. Disclosures: No relevant conflicts of interest to declare.

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Right-to-Left Shunts Are Unexpectedly Common in Adults with HbSS

Blood ◽

10.1182/blood.v128.22.3659.3659 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3659-3659 ◽

Cited By ~ 1

Author(s):

Bryan Christopher Hambley ◽

Rania Abdul Rahman ◽

Mary Ann O'Riordan ◽

Nathan Langer ◽

Seth Rotz ◽

...

Keyword(s):

Sickle Cell ◽

Research Funding ◽

Medical Center ◽

Adult Population ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Compound Heterozygous ◽

Continuous Variables ◽

Cardiopulmonary Complications ◽

The Impact

Abstract INTRODUCTION: Patients with homozygous sickle cell anemia (SCA) have frequent cardiopulmonary complications. The clinical prevalence and consequences of intracardiac or intrapulmonary right-to-left shunts in SCA are unknown. Here we report a retrospective examination of this complication, and clinical and laboratory correlates at clinical baseline, in an adult population with SCA. These shunts may be of particular relevance, due to the susceptibility of these patients to thrombosis and the role that desaturated hemoglobin plays in the underlying pathophysiology of this disease. METHODS: This single-institution study included 153 patients with homozygous HbSS, who are followed at Case-UH Medical Center, Cleveland. Clinical and laboratory data were gathered on patients who underwent an echocardiogram with bubble contrast. Echocardiograms were reviewed to confirm the presence, characteristics, and degree of a right-to-left shunt. Immediate (intracardiac) or delayed (intrapulmonary) shunts were identified; the latter were quantitated as <5, 5-15, or >15 bubbles visualized in the left heart. Continuous variables were described, using mean ± standard deviation (SD) and nominal variables were described as N (%). The relationship between clinical characteristics and echo results was determined using linear regression. All analyses were undertaken using SAS v9.4 The SAS Institute, Cary, NC. n.b. Compound heterozygous sickle cell disease patients showed this complication rarely, and were not examined systematically. RESULTS: 82/153 (53.6%) of studied SCA patients were female. Mean (SD) age in years was 32.2 (11.8). 90 (58.8%) patients had an echo with bubble study. In our population, 27 (17.6%) patients had an intracardiac shunt, 41 (26.8%) had an intrapulmonary shunt, and 22 (14.4%) had no shunt present; 63 (41.2%) patients did not have a bubble study. Mean (SD) LDH was 523.3 (318.1) for those with intracardiac shunts and 570.5 (205.4) for those with intrapulmonary shunts. Mean (SD) LDH for all shunt patients combined was 551.3 (255.9). Mean LDH (SD) for patients either with no shunt or no contrast echocardiogram was 415.5 (193.0). In a combined analysis, patients with shunts (N=68) showed a statistically higher baseline mean LDH when compared to a mean LDH of patients with either a negative bubble study or no bubble study (N=85), (551.3 vs 415.5, p<0.001). No difference was seen in prevalence of clinical outcomes of acute chest syndrome or stroke between groups. Laboratory markers of disease activity, such as absolute reticulocyte count or baseline hemoglobin were not different in shunt versus non-shunt patients. 8 patients had <5 bubbles in the left atrium or ventricle, 7 had 5-15 and 25 >15 bubbles. There was no evidence that this had an effect at clinical baseline, but the impact of such shunts during crises or multi-organ failure has not yet been assessed. A small number of individuals with shunts showed significant oxygen desaturation with exercise, but these were not statistically distinct from other groups. CONCLUSIONS: 68 patients with HbSS, or almost half of the adult SCA population, had right-to-left shunting on echocardiograms, either intracardiac or intrapulmonary, when evaluated at clinical baseline. These patients had significantly higher LDH than did patients with no bubble study or a negative bubble study, when evaluated in a combined post hoc analysis. The pathophysiology of these shunts is not known, but these have the potential to delay reoxygenation of sickle hemoglobin at clinical baseline and to facilitate right-to-left passage of fat or thrombotic emboli during clinical exacerbation. We are currently evaluating the potential impact of these shunts in patients with HbSS prospectively, both at baseline and during clinical exacerbation. Disclosures Schilz: Genetech: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Actelion: Consultancy, Speakers Bureau; United Therapeutics: Consultancy, Research Funding; Merck: Research Funding; Arena: Research Funding; Eiger: Research Funding.

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Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽

10.1182/blood.v97.11.3628 ◽

2001 ◽

Vol 97 (11) ◽

pp. 3628-3632 ◽

Cited By ~ 132

Author(s):

Alina Ferster ◽

Parvine Tahriri ◽

Christiane Vermylen ◽

Geneviève Sturbois ◽

Francis Corazza ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

History Of ◽

Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

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Clinical and Laboratory Benefits of Early Initiation of Hydroxyurea with Pharmacokinetic Guided Dosing for Young Children with Sickle Cell Anemia

Blood ◽

10.1182/blood-2018-99-112909 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 507-507 ◽

Cited By ~ 1

Author(s):

Patrick T. McGann ◽

Omar Niss ◽

Min Dong ◽

Anu Marahatta ◽

Tomoyuki Mizuno ◽

...

Keyword(s):

Young Children ◽

Sickle Cell ◽

Cystatin C ◽

Sickle Cell Anemia ◽

Research Funding ◽

Laboratory Data ◽

Advisory Board ◽

Young Cohort

Abstract Background: Hydroxyurea is now the standard of care for children with sickle cell anemia (SCA). Results from the BABY HUG study and recommendations from the 2014 NHLBI Guidelines have led to early initiation (increasingly before 1 year of age) of hydroxyurea for many patients. Given the known variability in hydroxyurea pharmacokinetics (PK), treatment response (HbF%), and maximum tolerated dose (MTD), we hypothesized that individualized dosing would provide the optimal treatment approach. Methods: The Therapeutic Response Evaluation and Adherence Trial (TREAT, ClinicalTrials.gov NCT02286154) is a prospective study of a personalized, PK-guided dosing model of hydroxyurea for children with SCA. Using population PK model-based Bayesian estimation, each participant's PK data are used to generate an individualized starting hydroxyurea dose that targets an area under the curve associated with actual MTD. Clinical follow-up and subsequent dose adjustments target MTD, usually defined by ANC<3.0x109/L. We analyzed clinical and laboratory data for TREAT participants who started hydroxyurea before 2 years of age, to allow for comparison to published results from BABY HUG, which included a similar young cohort but with conservative weight-based dosing of 20 mg/kg/day. TREAT participants had ongoing clinical and research evaluations of organ function, including transcranial doppler (TCD) studies, RBC pit counts, and cystatin C measurements. Results:The analysis of children starting hydroxyurea before 2 years of age included 33 participants (of 47 total TREAT enrollments), who contributed a total of 59.5 patient-years of hydroxyurea therapy. The mean age (±SD) at hydroxyurea initiation was 1.0±0.4 years of age. The average PK-guided, individualized starting dose was 27.8±5.3 mg/kg/day, higher than conventional and BABY HUG initial dosing (20 mg/kg/day). For children who have completed 12 months of therapy (n=24), effects in hematologic laboratory data are remarkable with average 35.9±8.9% HbF and hemoglobin concentration of 10.2±1.1 g/dL after 12 months of therapy (compared to 29.3±8.8% and 9.2±1.3 g/dL at baseline). The majority (70%) of these participants have HbF>30% and almost half achieved HbF>40% after 12 months of hydroxyurea. This hematological response is more robust than what was observed in BABY HUG (HbF=22.4%, Hb=9.1 g/dL after two years of therapy, Wang WC et al. Lancet 2011). In the TREAT cohort, there were no episodes of dactylitis, acute splenic sequestration, or stroke. There were 111 emergency room or sick outpatient clinic visits for this young cohort; 107 ED/clinic visits (without subsequent hospitalization) were for fever, URI symptoms, GI illness, or other non-specific complaints unrelated to SCA, while only 4 (3.6%) visits were for pain. There were 38 hospitalizations in 17 participants, mostly for routine evaluation of fever (66%), but no positive blood cultures and no admissions for febrile neutropenia. The average length of hospitalization was 2.8±2.4 days with 81% of participants discharged within 72 hours of admission. There were 3 episodes of acute chest syndrome in 2 patients, two of whom required PRBC transfusion. Including all types of visits, there were only 6 pain events, equivalent to 10.1 pain events per 100 patient-years, which is much lower than the published 94 events per 100 patient-years in the hydroxyurea treatment arm of BABY HUG (Thornburg CD et al. Blood 2012). There were 37 TCD exams performed in 16 participants, all normal except for one patient with conditional velocities that normalized with hydroxyurea. There were no significant differences from baseline to month 12 in either RBC pit counts or cystatin C values. Conclusions: Hydroxyurea initiation at an early age using PK-guided dosing provides significant clinical benefits for young children with sickle cell anemia. These TREAT study data suggest that initiating hydroxyurea around one year of life using a personalized dosing strategy can provide better clinical and laboratory benefits than starting at the conventional 20 mg/kg/day weight-based dose. Very high HbF levels are observed at modest and well-tolerated doses of hydroxyurea, perhaps because treatment was initiated before the process of HbF inactivation is complete. Continued long-term follow-up of these patients will determine whether these will be sustained and able to prevent both short- and long-term complications of SCA. Disclosures Malik: CSL Behring: Patents & Royalties. Quinn:Silver Lake Research Corporation: Research Funding; Global Blood Therapeutics: Research Funding; Amgen: Research Funding. Ware:Biomedomics: Research Funding; Nova Laboratories: Consultancy; Bristol Myers Squibb: Research Funding; Addmedica: Research Funding; Global Blood Therapeutics: Other: advisory board; Agios: Other: advisory board; Novartis: Membership on an entity's Board of Directors or advisory committees.

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The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: results of a 17-year, single-center trial (LaSHS)

Blood ◽

10.1182/blood-2009-05-221333 ◽

2010 ◽

Vol 115 (12) ◽

pp. 2354-2363 ◽

Cited By ~ 239

Author(s):

Ersi Voskaridou ◽

Dimitrios Christoulas ◽

Antonios Bilalis ◽

Eleni Plata ◽

Konstantinos Varvagiannis ◽

...

Keyword(s):

Sickle Cell ◽

Hospital Admissions ◽

Fetal Hemoglobin ◽

Acute Chest Syndrome ◽

Prolonged Administration ◽

Probability Of Survival ◽

Transfusion Requirements ◽

History Of

The aim of this prospective study was to evaluate the long-term efficacy and safety of hydroxyurea (HU) in patients with sickle cell disease (SCD). Thirty-four patients with sickle cell anemia (hemoglobin S [HbS]/HbS), 131 with HbS/β0-thal, and 165 with HbS/β+-thal participated in this trial. HU was administered to 131 patients, whereas 199 patients were conventionally treated. The median follow-up period was 8 years for HU patients and 5 years for non-HU patients. HU produced a dramatic reduction in the frequency of severe painful crises, transfusion requirements, hospital admissions, and incidence of acute chest syndrome. The probability of 10-year survival was 86% and 65% for HU and non-HU patients, respectively (P = .001), although HU patients had more severe forms of SCD. The 10-year probability of survival for HbS/HbS, HbS/β 0-thal, and HbS/IVSI-110 patients was 100%, 87%, and 82%, respectively, for HU patients and 10%, 54%, and 66%, for non-HU patients. The multivariate analysis showed that fetal hemoglobin values at baseline and percentage change of lactate dehydrogenase between baseline and 6 months were independently predicted for survival in the HU group. These results highlight the beneficial effect of HU, which seems to modify the natural history of SCD and raise the issue of expanding its use in all SCD patients.

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Regional and Age Group Differences in Sickle Cell Anemia Hospitalization Rates among African-American Adults: 1990-2002.

Blood ◽

10.1182/blood.v106.11.2255.2255 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2255-2255

Author(s):

Carlton Haywood ◽

Sophie Lanzkron

Keyword(s):

African American ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Acute Chest Syndrome ◽

Age Group ◽

The South ◽

Annual Increase ◽

Hospitalization Rates ◽

Time Period ◽

The Impact

Abstract Background: In 1995, investigators from the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) published data demonstrating that patients on hydroxyurea (HU) experienced fewer hospitalizations, fewer incidences of acute chest syndrome, and required fewer blood transfusions than patients not receiving HU. The objective of this study was to look at national trends in sickle cell anemia (SCA) admissions since the publication of the MSH results. Methods: We examined data from the National Hospital Discharge Survey (NHDS) for the period 1990–2002. The NHDS is a nationally representative survey of non-federal short-stay hospitals in the U.S, which allows for the estimation of inpatient utilization data. Inclusion criteria for our analysis were African American race, age 18+ years, and the following ICD9 codes: 28261 and 28262 (sickle cell anemia with or without crisis). To control for population growth, denominators for the calculation of hospitalization rates were estimated using U.S. Census population estimates included in the NHDS dataset, and a SCA prevalence of 1 in 600 AA. Negative binomial regression models were used to test the statistical significance of trends in SCA hospitalization rates overall, and stratified by age group (18 to 23, 24 to 29, 30 to 35, 36 to 41, and 42+) and region (Northeast, Midwest, South, and West). A linear spline term was created for the year 1996 (one year after MSH publication) to compare annual changes in mean hospitalization rates for the periods pre (1990–1996) and post (1997–2002) MSH publication. Results: In the overall analyses, the hospitalization rate increased by 1.5% annually from 1990 to 2002 (p=0.062). The pre/post analysis for all patients found no statistical differences in the change in hospitalization rates pre (0.9% increase, p = 0.626) or post (1.2% increase, p = 0.729) MSH publication. In the stratified age group analyses, we found that 24 to 29 year olds experienced an overall mean annual increase in hospitalization rates of 7.1% (p < 0.001). However, when viewed pre/post MSH, we found that 24 to 29 year olds experienced a 14% mean annual increase in rates pre-MSH (p < 0.001), and a 12% mean annual decrease in rates post-MSH (p = 0.003). The reverse trend was true for 36 to 41 year olds, who experienced a mean annual decrease in rates of 17% pre-MSH (p < 0.001), and mean annual increase of 36% post-MSH (p < 0.001). No statistical differences in annual rates of change were found for the other age groups. Regionally, we found that the South experienced a 7% mean annual increase in its relative hospitalization rates (p < 0.001) for the entire time period. The South experienced a 2.5% mean annual increase in rates pre-MSH (p = 0.156), and a 9% annual increase in rates post-MSH (p = 0.006). The West saw a 7% decrease in rates for the overall time period (p = 0.001). The Midwest experienced a 6% mean annual increase in rates pre-MSH (p = 0.058), and an 11% decrease in mean annual rates post-MSH (p = 0.034). Conclusions: Estimates of national SCA hospitalization rates for black adults, after MSH publication suggests that there has not been an overall decrease in hospitalization rates when patients and the country are examined as a whole. However, there are important age group and regional differences that need to be explored further to better understand the impact HU has had on this population.

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The Eveluation of Pulmonary Functions in Children with Sickle Cell Anemia.

Blood ◽

10.1182/blood.v114.22.4628.4628 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4628-4628

Author(s):

Cem Kurt ◽

Ilgen Sasmaz ◽

Bulent Antmen ◽

Yurdanur Kilinc ◽

Sadi Kurdak ◽

...

Keyword(s):

Patient Group ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Exercise Test ◽

Acute Chest Syndrome ◽

Control Group ◽

Healthy Children ◽

Diffusion Test ◽

Pulmonary Functions

Abstract Abstract 4628 Aim In this study we evaluated to pulmonary functions and determined relations of these findings with clinical parameters in children with sickle cell anemia (SCA) who were at follow up in our pediatric heamatology clinic. Materials and Methods 24 children with sickle cell anemia and 9 healthy children as control group include to the study. Complete blood count, hemoglobin electrophoresis and biochemical values were eveluated for both groups. At pulmonology department, the carbonmonoxide diffusion test performing for both groups. At the same day spirometric respiratory function evaluation and exercise test performed both groups at department of sports physiology. The data recieved are compared statistics. Results HbS, HbF, SGPT, ferritin, total bilirubine, direkt bilirubine and Fe++ values were high at patient group (p<0.05). Hemoglobin and hematocrit values were low at patient group according to control group as expected (p<0.05). The number of SCA patient who had one-three venoocclusive crises (VOC) were 14 (58.3%), patient who had three or more VOC were 7 (29.2%) and patient who had no VOC were 3 (12.5%). The number of patient who had acute chest syndrome (ACS) were 5 (20.9%) and 19 patients had no ACS (79.1%). Ýmpaired isole carbonmonoxide diffusion test was established at the 62.5% of the patient's. At patient group, spirometric FEV1 and MEF25 measurement were found lower than the control group (p<0.05). At exercise test VO2/HR rate were lower for patient group (p<0.05). VE/VO2 rate (p=0.023) and R (p=0.016) measurement were found higher. Conclusion Pulmonary gas transfer was found difficult in patients with SCA. Respiratory airways established obstructed in spirometric evaluation. Obstructive defficiensies have to be follow up. Oxygen pulse and respiratory exchange rates were determined low and more oxygen usage was observed for aerobic metabolic activity. With these results, ýt can be say that chronic inflamation process at lung due to oxygen radicals and hipoksemia in sickle cell patients, the aerobic respiratory load was increased. Disclosures: No relevant conflicts of interest to declare.

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Hydroxyurea Reduces Conversion From Conditional to Abnormal TCD Velocities In Children with Sickle Cell Anemia (SCA)

Blood ◽

10.1182/blood.v116.21.270.270 ◽

2010 ◽

Vol 116 (21) ◽

pp. 270-270 ◽

Cited By ~ 1

Author(s):

Jennifer Rothman ◽

Shelly Burgett ◽

Russell E. Ware ◽

Courtney Thornburg

Keyword(s):

Sickle Cell ◽

Sickle Cell Anemia ◽

Stroke Prevention ◽

Normal Range ◽

Original Cohort ◽

Transfusion Therapy ◽

Hydroxyurea Treatment ◽

The Mean ◽

Flow Velocities

Abstract Abstract 270 The use of transcranial Doppler ultrasound (TCD), a non-invasive imaging technique, is now clearly established for detecting high risk of stroke in children with sickle cell anemia (SCA). Children with TCD flow velocities ≥200 cm/s have a 10% risk of primary stroke per year. For these children, chronic blood transfusions (CBT) are recommended and have been shown to reduce the risk of primary stroke by up to 90%. The incidence of stroke has decreased to 0.06–0.17 per 100 patient-years since the institution of TCD screening (Fullerton et al. Blood 2004; Enningul-Egham et al., J Pediatr 2010). Although patients with conditional TCDs (flow velocities 170–199 cm/s) have an estimated stroke risk of 2–5% annually, and their rate of conversion from conditional to abnormal is 23% over an 18 month period (Hankins JS et al., BJH 2008), there are no clinical guidelines for primary stroke prevention in this group. We previously conducted a prospective cohort study of hydroxyurea in 37 children with SCA and TCD velocities >140 cm/sec, and demonstrated that TCD velocities decreased significantly after starting hydroxyurea (Zimmerman et al., Blood 2007; NCT00402480). In order to determine if hydroxyurea provided sustained reductions in TCD velocities, we conducted a retrospective review of these 37 children in this original cohort who had elevated TCD velocities and long-term hydroxyurea treatment. The following data were abstracted from the medical record between April 2000 and September 2009: treatment with hydroxyurea and CBT; adherence with treatments; stroke and non-stroke neurological events; and TCD time-averaged mean velocities (TAMV) immediately prior to initiation of hydroxyurea and at the end of extended follow-up. The primary outcome was comparison of pre and post TCD TAMV using a paired t-test. The mean age of enrollment on the original study was 6.8 years (1.8-14.8) and the mean age at follow-up was 12.9 years (5.3-18.5). The mean follow-up was 5.8 years (0.8-8.5) with an overall follow up of 215.1 patient years. Twenty males and 17 females were enrolled. The mean hydroxyurea dose was 25.2 ± 5.6 mg/kg/day, with one patient discontinuing therapy after 15 months. At follow-up, the mean hemoglobin was 8.9 ± 1.2 g/dL and mean HbF was 16 ± 7.2%. Sustained decreases were observed in both the right MCA (164.8 ± 25.5 cm/s to 124.9 ± 35 cm/s, p<0.001) and left MCA (167.9 ± 25.2 cm/s to 126.9 ± 30 cm/s, p<0.001) for all 37 patients. For the 15 patients with conditional TCD velocities at enrollment, 13 had maximal TAMV that reverted to and were sustained in the normal range (185.8 ± 10.0 cm/s to 132.9 ± 14.5 cm/s, p<0.001). Two converted to abnormal TCD velocities at 1.6 years and 4.5 years for a conversion rate of 13%; one was non-adherent but the other was adherent with hemoglobin of 10.8 g/dL and HbF of 23.5%. These two patients were started on CBT and remain stroke free. There were no primary stroke events observed in the 15 subjects with conditional TCD velocities over a total of 78.1 patient years. Of the 5 patients who had abnormal TCD velocities on enrollment and whose parents refused CBT, 1 patient had a stroke after 0.8 years of hydroxyurea therapy. This was the only patient who continued to have abnormal TCD velocities at MTD, 7 months after starting hydroxyurea. The remaining 4 patients continued to have TCD velocities in the normal range off transfusion therapy over 26.3 patient years. Overall, these data illustrate that treatment with hydroxyurea at MTD in children with SCA and elevated TCD velocities resulted in significantly lower and sustained improvements in TCD velocities. Additionally, for children with conditional TCD velocities, hydroxyurea resulted in a lower than expected conversion to abnormal values, thereby sparing many children from CBT without any noted increase risk of stroke. Hydroxyurea did not, however, protect fully against stroke in one patient who had persistently abnormal TCD velocities and therefore CBT remains the standard of care in this population until larger randomized trials are conducted. Further studies are required to evaluate hydroxyurea for primary stroke prevention in children prior to conversion to abnormal TCD and in children who already have abnormal TCD. The currently funded TCD With Transfusions Changing to Hydroxyurea (TWiTCH) clinical trial, which is scheduled to begin enrollment in late 2010, will help answer this important clinical question. Disclosures: Off Label Use: Hydroxyurea is used to reduce complications of sickle cell anemia.

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Abstract 89: Incidence and Characteristics of Hemorrhagic Stroke Among Post-STOP Participants

Stroke ◽

10.1161/str.51.suppl_1.89 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Liza A Leykina ◽

Christine K Fox ◽

Nancy K Hills ◽

Julie Kanter ◽

Janet L Kwiatkowski ◽

...

Keyword(s):

Incidence Rate ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Hemorrhagic Stroke ◽

Laboratory Data ◽

Young Patients ◽

Incidence Rates ◽

Standards Of Care ◽

Multicenter Cohort Study

Introduction: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) changed standards of care for stroke screening and treatment of high-risk children with sickle cell anemia (SCA), reducing the risk of ischemic stroke. However, the incidence of hemorrhagic stroke in young patients with SCA in the post-STOP era remains poorly characterized. Methods: The Post-STOP multicenter cohort study collected follow-up data from prior participants (all with SCA) of the STOP or STOP II clinical trials. From 01/2012 – 05/2014, medical records analysts abstracted clinical, imaging and laboratory data collected after the STOP studies ended at 19 of the 26 original sites. Two stroke neurologists reviewed data to confirm hemorrhagic stroke, defined as primary spontaneous intracerebral, subarachnoid or intraventricular hemorrhage; we excluded traumatic hemorrhage or hemorrhagic conversion of ischemic infarcts. Incidence rates among those with no prior hemorrhagic stroke at the start of Post-STOP were calculated using survival analysis techniques. Results: Follow-up data were collected from 2,851 of 3,835 participants participated in the STOP trials. Patients (51% male) were a median age of 10.4 years (interquartile range [IQR] 6.8-14.1) at the start of Post-STOP. Over a median of 10.3 (IQR 7.3-11.4) years of follow-up, 35 patients with hemorrhagic stroke were identified (Table 1). The incidence rate was 63 per 100,000 person-years overall (95% CI 45-87). Stratified by age, the incidence rate per 100,00 person-years was 50 (95% CI 34-75) for children less than 18 years old and 134 (95% CI 74-243) for adults over the age of 50. Conclusion: In our cohort, we observed that the risk of hemorrhagic stroke in patients with SCA rises as patients age, most sharply after the first decade of life. Structural vascular abnormalities such as moyamoya syndrome and aneurysms are common etiologies for hemorrhage and screening may be warranted.

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