High Hb F level is associated with the risk of cerebral vasculopathy in a cohort of sickle cell children in Mayotte.

Abstract Background Understanding the genetics underlying the heritable subphenotypes of sickle cell anemia, specific to each population, would be prognostically useful and could inform personalized therapeutics. Methods This study aimed to describe the genetic modulators of sickle cell disease in a cohort of pediatric patients followed in Mayotte between 2007 and 2017. Results We included 190 children with 72% SS, 16% Sβ0-thalassemia and 12% Sβ+ thalassemia. The mean age was 9.5 (1.6-23.4) years; 10% of patients were lost to follow up. The Bantu haplotype was associated with an increase in hospitalizations and transfusions. The alpha-thalassemic mutation was associated with a decrease of hemolysis biological parameters (anemia, reticulocytes), and less cerebral vasculopathy. The SNPs BCL11A rs4671393, BCL11A rs11886868, BCL11A rs1427407 and HMIP rs9399137 were associated with the group of children with HbF> 10%. The survival analysis without occurrence of cerebral vasculopathy showed that the group of patients with HbF> 10% presented a significant risk of early onset of cerebral vasculopathy. Conclusions Although the sub-phenotypes were difficult to clearly distinguish in our study, a genotype-sub-phenotype link is emerging.

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Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease

Journal of Neurosurgery Pediatrics ◽

10.3171/2014.12.peds14522 ◽

2015 ◽

Vol 16 (1) ◽

pp. 64-73 ◽

Cited By ~ 23

Author(s):

Christoph J. Griessenauer ◽

Jeffrey D. Lebensburger ◽

Michelle H. Chua ◽

Winfield S. Fisher ◽

Lee Hilliard ◽

...

Keyword(s):

Sickle Cell ◽

Stroke Prevention ◽

Pediatric Patients ◽

Case Series ◽

Secondary Stroke Prevention ◽

Moyamoya Syndrome ◽

Cell Disease ◽

Transfusion Therapy ◽

The Mean

OBJECT Pediatric patients with sickle cell disease (SCD) and moyamoya syndrome (MMS) are at significant risk for cerebrovascular accidents despite chronic transfusion therapy. Encephaloduroarteriosynangiosis (EDAS) and encephalomyoarteriosynangiosis (EMAS) are additional therapeutic options for these patients. To date, the incidence of complications after and efficacy of EDAS and EMAS in stroke prevention in this population have been described in several institutional case series reports, but no randomized prospective trials have been reported. METHODS The authors retrospectively reviewed the cases of all pediatric patients at the University of Alabama at Birmingham with a history of homozygous hemoglobin S (HbS) and sickle cell/β-thalassemia (SB0 thalassemia) and on chronic transfusion therapy, including 14 patients with MMS who underwent EDAS or EMAS. RESULTS Sixty-two patients with SCD and on chronic transfusion therapy were identified. After exclusion of patients on chronic transfusion therapy for indications other than stroke prevention, 48 patients (77.4%) remained. Of those patients, 14 (29.1%) underwent EDAS or EMAS. Nine (18.8%) and 25 (52.1%) patients were on chronic transfusion therapy for primary or secondary stroke prevention, respectively, but did not undergo EDAS or EMAS. The 14 patients with SCD and radiological evidence of MMS and on chronic transfusion therapy for primary or secondary stroke prevention underwent 21 EDAS or EMAS procedures for progressive vascular disease (92.9% of patients), stroke (71.4%), and/or seizure (7.1%). The mean (± SD) time from initiation of chronic transfusion therapy to EDAS or EMAS was 76.8 ± 58.8 months. Complications included 1 perioperative stroke, 1 symptomatic subdural hygroma, 1 postoperative seizure, and 1 case of intraoperative cerebral edema that required subsequent cranioplasty. Before EDAS or EMAS, the stroke rate was calculated to be 1 stroke per 7.8 patient-years. One additional stroke occurred during the follow-up period (mean follow-up time 33.7 ± 19.6 months), resulting in a post-EDAS/EMAS stroke rate of 1 stroke per 39.3 patient-years, a 5-fold reduction compared with that in the pre-EDAS/EMAS period. The patients’ mean pre-EDAS/EMAS HbS level of 29.5% ± 6.4% was comparable to the mean post-EDAS/EMAS HbS level of 25.5% ± 6.1% (p = 0.104). CONCLUSIONS The results of this retrospective case series in a large cohort of pediatric patients with SCD and MMS suggest that EDAS/EMAS provides a stroke-prevention benefit with an acceptably low morbidity rate. Given the combined experience with EDAS and EMAS for this indication at this and other institutions, a prospective clinical trial to assess their efficacy compared with that of chronic transfusion therapy alone is warranted.

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Variability of Prognostic Results Based on Biological Parameters in Sickle Cell Disease Cohort Studies in Children: What Should Clinicians Know?

Children ◽

10.3390/children8020143 ◽

2021 ◽

Vol 8 (2) ◽

pp. 143

Author(s):

Julie Sommet ◽

Enora Le Roux ◽

Bérengère Koehl ◽

Zinedine Haouari ◽

Damir Mohamed ◽

...

Keyword(s):

Statistical Analysis ◽

Sickle Cell Disease ◽

Cohort Studies ◽

Statistical Methods ◽

Sickle Cell ◽

Biological Parameters ◽

Analysis Method ◽

Cell Disease ◽

Statistical Analysis Method

Background: Many pediatric studies describe the association between biological parameters (BP) and severity of sickle cell disease (SCD) using different methods to collect or to analyze BP. This article assesses the methods used for collection and subsequent statistical analysis of BP, and how these impact prognostic results in SCD children cohort studies. Methods: Firstly, we identified the collection and statistical methods used in published SCD cohort studies. Secondly, these methods were applied to our cohort of 375 SCD children, to evaluate the association of BP with cerebral vasculopathy (CV). Results: In 16 cohort studies, BP were collected either once or several times during follow-up. The identified methods in the statistical analysis were: (1) one baseline value per patient (2) last known value; (3) mean of all values; (4) modelling of all values in a two-stage approach. Applying these four different statistical methods to our cohort, the results and interpretation of the association between BP and CV were different depending on the method used. Conclusion: The BP prognostic value depends on the chosen statistical analysis method. Appropriate statistical analyses of prognostic factors in cohort studies should be considered and should enable valuable and reproducible conclusions.

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Ischemic Stroke in Children and Young Adults with Sickle Cell Disease (SCD) in the Post-STOP Era

Blood ◽

10.1182/blood.v126.23.68.68 ◽

2015 ◽

Vol 126 (23) ◽

pp. 68-68 ◽

Cited By ~ 3

Author(s):

Janet L. Kwiatkowski ◽

Julie Kanter ◽

Heather J. Fullerton ◽

Jenifer Voeks ◽

Ellen Debenham ◽

...

Keyword(s):

Ischemic Stroke ◽

High Risk ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Stroke Prevention ◽

Cell Disease ◽

Clinical Series ◽

The Mean

Abstract Background: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. To identify children at high-risk of stroke, annual TCD screening is recommended from ages 2 to 16 years, with more frequent monitoring if the result is not normal. A reduction in stroke incidence in children with SCD has been reported in several clinical series and analyses utilizing large hospital databases when comparing rates before and after the publication of the STOP study in 1998. We sought to determine the rate of first ischemic stroke in a multicenter cohort of children who had previously participated in the STOP and/or STOP 2 trials and to determine whether these strokes were screening or treatment failures. Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3,835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 ranged from a single screening TCD to randomization. STOP 2 also had an observational arm for children on CRCT for abnormal TCD whose TCD had not reverted to normal. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both trials. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3,539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 (depending on site) including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two vascular neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results, reviewed source records to confirm all ischemic strokes, defined as a symptomatic cerebral infarction; discordant opinions were resolved through discussion. For the first Post-STOP ischemic stroke, prior TCD result and treatment history subsequently were analyzed. Results: Of the 3,539 subjects, follow-up data were available for 2,850 (81%). Twelve children who had a stroke during STOP or STOP2 were excluded from these analyses resulting in data on 2,838 subjects. The mean age at the start of Post-STOP was 10.5 y and mean duration of follow-up after exiting STOP/2 was 9.1 y. A total of 69 first ischemic strokes occurred in the Post-STOP observation period (incidence 0.27 per 100 pt years). The mean age at time of stroke was 14.4±6.2 (median 13.8, range 3.5-28.9) y. Twenty-five of the 69 patients (36%) had documented abnormal TCD (STOP/2 or Post-STOP) prior to the stroke; 15 (60%) were receiving CRCT and 9 (36%) were not (treatment data not available for 1 subject). Among the 44 subjects without documented abnormal TCD, 29 (66%) had not had TCD re-screen in the Post-STOP period prior to the event; 7 of these 29 (24%) were 16 y or older at the start of Post-STOP, which is beyond the recommended screening age. Four of the 44 (9%) patients had inadequate TCD in Post-STOP (1 to 10.7 y prior to event). Six (14%) had normal TCD more than a year before the event (1.2 - 4 y); all but one of these children were younger than 16 y at the time of that TCD. Only 5 (11%) had a documented normal TCD less than 1 year prior to the event. Conclusions: In the Post-STOP era, the rate of first ischemic stroke was substantially lower than that reported in the Cooperative Study of Sickle Cell Disease, prior to implementation of TCD screening. Many (39%) of the Post-STOP ischemic strokes were associated with a failure to re-screen according to current guidelines, while only 11% occurred in children who had had recent low-risk TCD. Among those known to be at high risk prior to stroke, treatment refusal or inadequate treatment may have contributed. While TCD screening and treatment are effective at reducing ischemic stroke in clinical practice, significant gaps in screening and treatment, even at sites experienced in the STOP protocol, remain to be addressed. Closing these gaps should provide yet further reduction of ischemic stroke in SCD. Disclosures No relevant conflicts of interest to declare.

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Development of Algorithm for Clinical Management of Sickle Cell Bone Disease: Evidence for a Role of Vertebral Fractures in Patient Follow-up

Journal of Clinical Medicine ◽

10.3390/jcm9051601 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1601 ◽

Cited By ~ 1

Author(s):

Lucia De Franceschi ◽

Daniele Gabbiani ◽

Andrea Giusti ◽

Gianluca Forni ◽

Filippo Stefanoni ◽

...

Keyword(s):

Bone Density ◽

Sickle Cell ◽

Bone Disease ◽

Vertebral Fractures ◽

Cell Disease ◽

High Incidence ◽

The Mean

Sickle-cell disease (SCD) is a worldwide distributed hemoglobinopathy, characterized by hemolytic anemia associated with vaso-occlusive events. These result in acute and chronic multiorgan damage. Bone is early involved, leading to long-term disability, chronic pain and fractures. Here, we carried out a retrospective study to evaluate sickle bone disease (SBD) in a cohort of adults with SCD. We assessed bone density, metabolism and turnover. We also evaluated the presence of fractures and the correlation between SCD severity and skeletal manifestations. A total of 71 patients with SCD were analyzed. The mean age of population was 39 ± 10 years, 56% of which were females. We found osteoporosis in a range between 7% and 18% with a high incidence of vertebral fractures. LDH and AST were predictive for the severity of vertebral fractures, while bone density was not. Noteworthy, we identified -1.4 Standard Deviations T-score as the cutoff for detecting the presence of fractures in patients with SCD. Collectively our data allowed us to develop an algorithm for the management of SBD, which may be useful in daily clinical practice to early intersect and treat SBD.

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NT-Pro Brain Natriuretic Peptide Levels and the Risk of Stroke and Death in the Cooperative Study of Sickle Cell Disease.

Blood ◽

10.1182/blood.v114.22.1541.1541 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1541-1541 ◽

Cited By ~ 3

Author(s):

Roberto F Machado ◽

Mariana Hildescheim ◽

Laurel Mendelsohn ◽

Gregory J Kato ◽

Mark T Gladwin

Keyword(s):

High Risk ◽

Sickle Cell Disease ◽

Incidence Rate ◽

Sickle Cell ◽

Pediatric Patients ◽

Cooperative Study ◽

Cell Disease ◽

Risk Of Death ◽

History Of

Abstract Abstract 1541 Poster Board I-564 Background Elevations in NT-proBNP levels are associated with hemolysis-associated pulmonary hypertension and mortality in adults with sickle cell disease. The association of this vasculopathy with the risk of stroke has not been explored. The Cooperative Study of Sickle Cell Disease (CSSCD) is the largest cohort of adult and pediatric patients with sickle cell disease with the longest median follow-up. Using stored plasma samples from patients enrolled in the CSSCD, we tested the hypothesis that adult patients with high levels of NT-proBNP would be at a high risk of death and stroke and that pediatric patients with a high BNP might be at a high risk of stroke. Methods A threshold NT-pro-BNP value previously identified to predict mortality in adults with sickle cell disease was used to determine the association between the risk of stroke and mortality in a cohort of 758 participants (pediatric cohort, n=428 and adult cohort, n=330) in the CSSCD. Results The prevalence of an abnormal NT-proBNP level ≥ 160 pg/ml was 27.6 % in patients in the adult CSSCD cohort. The prevalence of a NT-proBNP level ≥ 160 pg/ml was 27.4 % in the pediatric cohort, which is at least in part explained by known higher normal NT-proBNP levels in children, especially during the first year of life. The incidence of the development of a high NT-proBNP level in subjects with a normal baseline level was 6 % over a mean follow-up time of 5.9 years (incidence rate per 100-person years of 1.03) in the pediatric cohort and 16.5 % over a mean follow-up time of 1.9 years in the adult cohort (incidence rate per 100-person years of 8.59). In subjects with normal baseline levels, multivariate logistic regression analysis of clinical and laboratory factors associated with the development of a high NT-proBNP level included increasing age (OR 3.43, 95% CI 1.6-7.2, P = 0.001), low hemoglobin (OR 0.47, 95% CI 0.3-0.7, P < 0.001), high white blood cell count (OR 1.69, 95% CI 1.05-2.7, P = 0.03), high creatinine (OR 2.22, 95% CI 1.1-4.3, P = 0.02), blood urea nitrogen (OR 1.64, 95% CI 1.2-2.3, P = 0.004), alanine aminotransferase (OR 1.26, 95% CI 1.01-1.6, P = 0.04) and uric acid levels (OR 2.32, 95% CI 1.4-3.8, P = 0.001), and history of leg ulcers (OR 7.46, 95% CI 2.0-28.5, P = 0.003). Elevated NT pro-BNP levels were associated with indices of hemolytic anemia (hemoglobin: OR 0.33, 95% CI 0.2-0.4, P < 0.001) and a history of stroke (OR 1.86, 95% CI 0.9-3.7, P = 0.02). An NT-pro-BNP level ≥160 pg/ml was a predictor of mortality (RR 6.24, 95% CI 2.9-13.3, P < 0.001) and stroke (RR 3.84, 95 % CI 1.0-14.3, P = 0.05) in this cohort. Conclusions A high NT-proBNP level is a major risk factor for death in patients with sickle cell disease. These findings provide further support for a mechanistic link between hemolytic anemia and the development of cardiovascular complications in this patient population. Finally, we have identified a novel widely available biomarker of the risk of death and stroke in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

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Timing of the Initiation of Hydroxyurea and Hematologic Outcomes in Patients with Sickle Cell Disease (SCD)

Blood ◽

10.1182/blood.v120.21.1004.1004 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1004-1004

Author(s):

Shaina Willen ◽

Nirmish Shah ◽

Courtney Thornburg ◽

Jennifer Rothman

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Significant Relationship ◽

Medical Center ◽

Fetal Hemoglobin ◽

Clinical Severity ◽

Cell Disease ◽

Younger Age ◽

The Mean

Abstract Abstract 1004 Hydroxyurea (HU) is approved for use in adults with Sickle Cell Disease (SCD) and increases the production of fetal hemoglobin (HbF). Increased HbF is associated with decreased clinical severity in adults and children with SCD, such as decreased numbers of vaso-occlusive events, transfusions, and hospitalizations. Higher HbF at initiation of HU is predictive of HbF response, but association between age of hydroxyurea initiation and HbF response has not been investigated. We hypothesize that starting hydroxyurea at an early age may improve hematological and clinical response. In order to determine if younger age at hydroxyurea initiation affects the percentage of HbF achieved with hydroxyurea, we conducted a retrospective cohort study. We identified subjects enrolled in the Duke University Medical Center Comprehensive Sickle Cell program who initiated hydroxyurea when they were less than 17.99 years of age and were prescribed hydroxyurea for at least six months. The following data were abstracted from the medical record between December 1996 and April 2011: age, hemoglobin, percentage HbF, and mean corpuscular volume (MCV) at start of HU and at maximum tolerated dose (MTD) of HU therapy. The correlation coefficient and p-values for various parameters were calculated. Seventy-three patients (41 males and 32 females) were included in the analysis. The mean age at hydroxyurea initiation was 5.5 years (1.2–14.1). The mean hydroxyurea dose at MTD was 28.6 ± 3.2 mg/kg/day. At initiation, the mean hemoglobin was 8.2 ± 1.2 g/dL, the mean MCV was 83±7.4 fl and mean HbF was 10 ± 5.7%. At MTD, the mean hemoglobin was 9.4 ± 1.1 g/dL, the mean MCV was 99 ± 11.1 fl, and the mean HbF was 21.7 ± 9.4%. As expected, at MTD, an elevated MCV was correlated with elevated fetal hemoglobin (r2= 0.19, p= 0.0001) [Table 1]. There was a statistically significant relationship between the age at HU initiation and the HbF at MTD (r2= 0.08, p= 0.015) [Figure 1] as well as the age at HU initiation and the hemoglobin at MTD (r2= 0.19, p= 0.016). The relationship between the age at starting HU and the overall change in HbF (DHbF) was not statistically significant (r2= 0.01, p= 0.41). There was not a statistically significant relationship between age at HU initiation and the MTD of HU (r2= 0.003, p= 0.61). The 6 patients started on HU at age less than 2 years (mean 1.5 ± 0.3 years) maintained a mean elevated HbF of 19.1 ± 5% at last documented follow-up with follow-up ranging from 1.4–13 year of uninterrupted hydroxyurea use. Starting hydroxyurea therapy at a younger age appears to improve HbF response as measured at MTD, although there is variability in the level of fetal hemoglobin attained. There is not an association seen with the DHbF or dose at MTD and age at hydroxyurea initiation. In summary, starting hydroxyurea at a younger age, when HbF is >20%, leads to persistence of HbF production and overall improvement in hematological efficacy. This was not simply the result of achieving MTD at a younger age before physiologic decline of HbF. Disclosures: Off Label Use: Hydroxyurea for complications of sickle cell disease in pediatrics. Shah:Eisai: Research Funding; Adventrx: Consultancy.

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Effectiveness of surgical revascularization for stroke prevention in pediatric patients with sickle cell disease and moyamoya syndrome

Journal of Neurosurgery Pediatrics ◽

10.3171/2017.1.peds16576 ◽

2017 ◽

Vol 20 (3) ◽

pp. 232-238 ◽

Cited By ~ 13

Author(s):

Wuyang Yang ◽

Risheng Xu ◽

Jose L. Porras ◽

Clifford M. Takemoto ◽

Syed Khalid ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Stroke Prevention ◽

Pediatric Patients ◽

Moyamoya Syndrome ◽

Cell Disease ◽

Surgical Revascularization ◽

Transfusion Therapy ◽

Indirect Revascularization

OBJECTIVESickle cell disease (SCD) in combination with moyamoya syndrome (MMS) represents a rare complication of SCD, with potentially devastating neurological outcomes. The effectiveness of surgical revascularization in this patient population is currently unclear. The authors’ aim was to determine the effectiveness of surgical intervention in their series of SCD-MMS patients by comparing stroke recurrence in those undergoing revascularization and those undergoing conservative transfusion therapy.METHODSThe authors performed a retrospective chart review of patients with MMS who were seen at the Johns Hopkins Medical Institution between 1990 and 2013. Pediatric patients (age < 18 years) with confirmed diagnoses of SCD and MMS were included. Intracranial stroke occurrence during the follow-up period was compared between surgically and conservatively managed patients.RESULTSA total of 15 pediatric SCD-MMS patients (28 affected hemispheres) were included in this study, and all were African American. Seven patients (12 hemispheres) were treated with indirect surgical revascularization. The average age at MMS diagnosis was 9.0 ± 4.0 years, and 9 patients (60.0%) were female. Fourteen patients (93.3%) had strokes before diagnosis of MMS, with an average age at first stroke of 6.6 ± 3.9 years. During an average follow-up period of 11.6 years, 4 patients in the conservative treatment group experienced strokes in 5 hemispheres, whereas no patient undergoing the revascularization procedure had any strokes at follow-up (p = 0.029). Three patients experienced immediate postoperative transient ischemic attacks, but all recovered without subsequent strokes.CONCLUSIONSIndirect revascularization is suggested as a safe and effective alternative to the best medical therapy alone in patients with SCD-MMS. High-risk patients managed on a regimen of chronic transfusion should be considered for indirect revascularization to maximize the effect of stroke prevention.

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Validation and Feasibility of a Point of Care Screening Test for Sickle Cell Disease in a Resource Constrained Setting — a New Frontier

Blood ◽

10.1182/blood-2018-99-118876 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2229-2229 ◽

Cited By ~ 1

Author(s):

Christopher Mwaniki Wanjiku ◽

Festus Njuguna ◽

Fredrick Chite Asirwa ◽

Cyrus Njuguna ◽

Chris Roberson ◽

...

Keyword(s):

Sickle Cell ◽

Screening Test ◽

Point Of Care ◽

Screening Tests ◽

Cell Disease ◽

Positive Screen ◽

Sub Saharan ◽

Study Participants ◽

Lost To Follow Up

Abstract Introduction and Objectives Sickle cell disease (SCD) is a neglected tropical disease disproportionally affecting malaria endemic regions of sub-Saharan Africa. Estimated to affect up to 3% of the population in some areas, 50-90% of children affected with SCD die before age five due to lack of diagnosis and preventative care. Early screening and intervention improves survival, but is not the standard of care throughout much of the continent. Kenya, like several other sub-Saharan African countries, has piloted newborn screening (NBS) for SCD, but NBS programs based on the infrastructure and approaches in Western countries have proved challenging to replicate in resource constrained environments (RCEs). As many as 50% of patients who have screened positive for SCD in programs throughout Africa are lost to follow-up. The recent development of affordable, point of care (POC) screening tests have provided an alternative approach to testing for SCD in RCEs. This study aimed to determine the validity and feasibility of utilizing a POC SCD screening test, HemoTypeSC™ (HTSC) in a RCE, to determine the prevalence of SCD in western Kenya, and to determine the rate of attendance at follow-up clinic after a positive POC screening test for SCD. Methodology Asymptomatic patients from birth through five years of age were approached for study enrollment in the pediatric vaccine clinic of Homabay County Referral Hospital (HCRH). 700 study participants were screened at HCRH over a 6 month period using HTSC. Isoelectric focusing (IEF) was run on a sample collected contemporaneously with the sample collected for testing with HTSC . At least one parent of each study participant was consented and counselled regarding SCD. Participants with a positive screen for either SCD or Sickle Cell Trait (SCT) were asked to return for confirmatory testing with Hb Electrophoresis (HBE). The HTSC screening results were compared to IEF and HBE results to determine the specificity and sensitivity, respectively. Samples yielding discordant results between HTSC or IEF and HBE were referred for molecular genotyping. Study participants with confirmed SCD were scheduled to attend a follow-up clinic. Participants unreachable by phone after at least ten attempts were declared lost to follow up. Results The median age of participants was 14 months (IQR: 5,30), 387(55.3%) were male. 18 patients had discordant results between screening tests and HBE and are pending molecular testing. 214 (30.6%) subjects screened positive for SCT or SCD on HTSC . 155 of these patients returned for HBE testing. The sensitivity of HTSC from the 155 receiving HBE testing was 92.1% for SCD and 95.0% for SCT. By comparison, the sensitivity of the concurrent IEF testing was 90.2% for SCD and 90.0% for SCT. The specificity of HTSC was 95.0% for SCD and 89.1% for SCT (as compared to IEF specificity of 92.0% and 89.1% for SCD and SCT, respectively). 9.6% of the subjects were found to have SCD, 20% had SCT. Of those with a positive screen for SCT or SCD, 191 (88%) were successfully contacted. 40 (78.4%) of those subjects confirmed to have SCD attended a follow-up clinical appointment. These data are summarized in Table 1. The majority of participants contacted who did not present for HBE testing or attend follow-up clinic cited socioeconomic factors as the main impediment. Discussion and Conclusions HTSC was found to be a feasible, valid POC screening test for SCD. The test was easy to perform and interpret, and facilitated prompt delivery of results. Education and counseling about SCD at the time of a positive screen led to a high rate of attendance at follow-up clinic. Further investigation is required to determine the long-term effect of POC testing on survival and quality of life outcomes. The prevalence of SCD in this cohort was among the highest rates reported in the literature. Though consanguinity was not documented as part of this study, it likely contributed to the high Hb SS frequency. These results support the notion that there is substantial regional variability in the frequency of Hb SS compared to national estimates extrapolated from Hb S frequency and highlight the criticality of more systematic, broad-based screening and treatment programs in targeted sub-Saharan African locations. Figure. Figure. Disclosures Wanjiku: Silverlake Research Cooperation: Research Funding.

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Adherence patterns among patients receiving healthcare services in the Muhimbili Sickle Cell Cohort, Tanzania

10.21203/rs.3.rs-16167/v1 ◽

2020 ◽

Author(s):

Upendo Masamu ◽

Raphael Zozimus Sangeda ◽

Daniel Kandoga ◽

Jesca Ondego ◽

Florah Ndobho ◽

...

Keyword(s):

Survival Analysis ◽

Sickle Cell ◽

Parametric Method ◽

Healthcare Services ◽

Rank Test ◽

P Value ◽

Mean Cell Volume ◽

Loss To Follow Up ◽

Lost To Follow Up

Abstract Background: Monitoring of patient’s clinical attendance is one of the crucial means that is used to improve adherence to care and treatment among the Sickle Cell Disease (SCD) patients. Adherence to care has been shown to improve health outcomes in SCD patients. However, these benefits cannot be achieved when patients are lost to follow-up to care. Method : We analyzed data on loss to follow up to determine the patterns among sickle cell patients registered at Muhimbili Sickle Cell Cohort (MSC), in Dar es Salaam, Tanzania. Data was aggregated and analysed using R software and Microsoft Excel Spreadsheet. Survival analysis techniques, both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox’s proportional hazard model), were used. A p-value of 0.05 was considered significant to make a strong inference of the analysis. Results: 5476 SCD patients were registered at MSC from 2004 to 2016, 3350 (58.13%) were actively participating in clinics while, 2126 (41.87%) were inactive, out of which 35.19% were lost to follow-up. From the survival analysis results, patients who were between 5 to 17 years were more likely to be lost to follow-up than the rest with a hazard ratio of 2.65 times more than those who were above 18 years. Patients with mean cell volume above 77.73 fL and white blood cell above 15.73(10ˆ3/uL) were more likely to be loss to follow-up than those below average. Conclusion: Loss to follow-up is evident in a cohort of patients in long term comprehensive care follow-up. It is, therefore, necessary to design interventions that minimize its impacts. Suggested solutions might include training of the health care workers, more emphasis on newborn screening and advocacy to patients regarding the effect of loss to follow-up.

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Progression of Pulmonary Hypertension in Patients with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.3187.3187 ◽

2005 ◽

Vol 106 (11) ◽

pp. 3187-3187 ◽

Cited By ~ 3

Author(s):

Kenneth I. Ataga ◽

Charity Moore ◽

Susan Jones ◽

Oludamilola Olajide ◽

Dell Strayhorn ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Left Ventricular ◽

Right Atrial ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Original Cohort ◽

The Mean

Abstract Introduction: The prevalence of pulmonary hypertension (PHT) is high in patients with sickle cell disease (SCD). Although most patients have only mild increases in their pulmonary artery systolic pressure (PASP), the presence of PHT is strongly associated with an increased risk of death. While PHT seen in SCD is thought to progress over time, both the rate of development of PHT and the factors that affect disease progression remain unknown. Methods: The 41 subjects in this study were drawn from an original cohort of 60 patients followed in the Sickle Cell Clinic at UNC-Chapel Hill. All patients were previously evaluated for PHT (defined using an age-, sex-, and BMI-adjusted reference range). Of the 60 patients in the original cohort, six are now deceased and 13 others were not available for repeat evaluation. The PASP was determined using Doppler echocardiography and then applying the modified Bernoulli equation (PASP = 4V2 + right atrial pressure). Individuals were not studied if they: 1) showed clinical evidence of left ventricular failure; 2) had a recent acute illness (e.g., vaso-occlusive crisis); or 3) had experienced an episode of acute chest syndrome within the preceding 4 weeks. Means and standard deviations were calculated for all measures at the time of initial evaluation and at the time of follow-up. Results: Of the 41 subjects in our study, PHT was originally present in 12, while no evidence of PHT was present in 29. Of the 29 subjects who initially had no evidence of PHT, 4 (or 14%) have now developed PHT (mean follow-up period of 3.3 ± 0.4 years). In these 4 subjects, the mean PASP at the time of initial and follow-up evaluations respectively were: 37.0 ± 2.0 mm Hg vs. 55.8 ± 11.0 mm Hg. The patients who developed PHT during the course of the study had lower systolic BP (143 ± 12 mm Hg vs. 128 ± 12 mm Hg), lower fetal hemoglobin levels (6.2 ± 5.7 % vs. 4.2 ± 3.7 %), and higher platelet counts (276 ± 119 X 103/μL vs. 426 ± 96 X 103/μL) at the time of their follow-up analyses. By contrast, 3 of the 12 subjects (or 25%) who were thought to have PHT at the time of their original evaluations were found to have normal PASP determinations at the time of their repeat echocardiograms (mean follow-up period of 3.2 ± 0.6 years). In these latter 3 subjects, the mean PASP values at the time of the initial and follow-up evaluations respectively were: 40.0 ± 4.6 mm Hg vs. 33.7 ± 4.7 mm Hg. Conclusion: In this small group of patients with SCD, we found that PHT developed in 14% of subjects who had no evidence of PHT 3 years earlier. Based on this observation, it seems that periodic echocardiograms to screen for the development of PHT would be appropriate. On the other hand, our observation that some patients initially classified as having PHT failed to have elevated PASP measurements at the time of follow-up illustrates the limitation of a single echocardiographic evaluation in establishing this diagnosis. Because of the increase in PASP that occurs during acute vaso-occlusive episodes, and the difficulty usually encountered in distinguishing steady state from crisis, the initial elevation of the PASP in these patients could have resulted from sub-clinical crisis states. For these reasons, a patient found to have an elevated PASP at the time of a screening echocardiogram should have a repeat study, and perhaps a right heart catheterization, before the diagnosis of PHT is firmly established.

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