Background
In malaria‐endemic countries in West Africa, sickle cell disease (SCD) contributes to childhood mortality. Historically, Liberia had regions wherein hemoglobin S and beta‐thalassemia trait ...were mutually exclusive. Data on hemoglobinopathies in the Monrovia, the capital, are outdated and do not reflect urban migration. Updating the epidemiology of SCD is necessary to plan a public health and clinical agenda. Neither newborn screening (NBS) nor screening tools were available in country. This pilot study aimed to determine the feasibility of NBS using a South–South partnership and define the incidence of sickle cell trait (SCT) and SCD in Monrovia.
Procedure
This descriptive epidemiologic feasibility study collected dried blood spots from 2,785 consecutive newborns delivered at a hospital in Monrovia. Samples were analyzed by isoelectric focusing at a regional reference laboratory. Infants with SCD were referred for preventive care.
Results
SCT occurred in 10.31% of infants screened. SCD occurred in 33 infants screened 1.19% (95% confidence interval CI: 0.79–1.59%) (FS: 28/33, FSB: 2/33, FSA: 2/33, FSX: 1/33). There were no infants with FSC phenotype observed. Nonsickling hemoglobin phenotypes “FC” and “F” were each present in three infants screened. Seventy‐six percent of infants with SCD were brought to care, demonstrating the feasibility of our approach.
Conclusions
The incidence of SCD and other hemoglobinopathies remains high in Liberia. Additional studies are needed to clarify sickle genotypes and identify the contribution of silent beta‐thalassemia alleles. By developing regional partnerships, countries similar to Liberia can acquire current data to inform NBS as an important public health initiative toward improving child health.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
As recently as the 1970s, children born with sickle cell disease (SCD) were unlikely to survive into adulthood. With advances in medical care, most patients now survive childhood and live into their ...forties or beyond
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,
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. A better transition from pediatric- to adult-focused care is therefore increasingly important
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. Despite recent awareness of the importance of transition by the SCD community, little is known about existing transition programs. We conducted a survey of pediatric sickle cell clinics to describe current transition practices and identify areas for improvement. Survey topics included program demographics, transition logistics, assessment of patient transition readiness and independence, transition preparation, and program evaluation. Twenty-three clinics (77%) report having a transition program, although half have been in place for under 2 years. There is wide variation in specific transition practices. Most centers (97%) have an identified accepting adult provider, however, only 60% routinely transfer their patients to an adult hematologist specializing in SCD. Although there has been a recent effort to establish transition programs in pediatric sickle cell clinics, specific practices vary widely. As anticipated, lack of an accepting adult hematologist with an interest in SCD emerged as a common barrier to transition.
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Sickle cell disease (SCD) requires coordinated, specialized medical care for optimal outcomes. There are no United States (US) guidelines that define a pediatric comprehensive SCD program. We report ...a modified Delphi consensus‐seeking process to determine essential, optimal, and suggested elements of a comprehensive pediatric SCD center. Nineteen pediatric SCD specialists participated from the US. Consensus was predefined as 2/3 agreement on each element's categorization. Twenty‐six elements were considered essential (required for guideline‐based SCD care), 10 were optimal (recommended but not required), and five were suggested. This work lays the foundation for a formal recognition process of pediatric comprehensive SCD centers.
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Current screening guidelines may not be adequate to identify iron deficiency (ID) and iron deficiency anemia (IDA) in adolescent and young adults. Adolescent and young adult outpatients from 4 ...hospital-based clinics (N = 493) reported on diet, health, and bleeding, and had phlebotomy for iron and hematologic tests. We examined sex-specific factors associated with ID and IDA and ability of universal and risk factor–based screening using hemoglobin and hemoglobin plus ferritin to detect ID and IDA. Among females (n = 350), 34.6% had ID and 6.3% had IDA. Nearly 1 in 3 females with ID had no risk factors. Among males, 12.6% had ID; none had IDA. More than 1 in 3 males with ID did not have risk factors. Current screening approaches would have missed ID in 47% to 82% of females and 95% to 100% of males. ID was prevalent in both male and female adolescents and young adult outpatients. New approaches to screening for ID are needed to accurately evaluate iron status in this population.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Congenital disorders of glycosylation (CDGs) are clinically heterogeneous disorders defined by a decreased ability to modify biomolecules with oligosaccharides. Critical disruptions in protein ...recognition, interaction, binding, and anchoring lead to broad physiological effects. Patients present with endocrinopathy, immunodeficiency, hepatopathy, coagulopathy, and neurodevelopmental impairment. Patients may experience mortality/morbidity associated with shock physiology that is frequently culture negative and poorly responsive to standard care. Oedema, pleural and pericardial effusions, ascites, proteinuria, and protein‐losing enteropathy are observed with an exaggerated inflammatory response. The negative serum protein steady state results from several mechanisms including reduced hepatic synthesis and secretion, increased consumption, and extravasation. Disruption of the glycocalyx, a layer of glycosylated proteins that lines the endothelium preventing thrombosis and extravasation, is a suspected cause of endothelial dysfunction in CDG patients. We performed a retrospective review of CDG patients admitted to our institution with acute illness over the past 2 years. Longitudinal clinical and laboratory data collected during the sick and well states were assessed for biomarkers of inflammation and efficacy of interventions. Six patients representing 4 CDG subtypes and 14 hospitalisations were identified. Acute D‐dimer elevation, proteinuria, decreased serum total protein levels, coagulation proteins, and albumin were observed with acute illness. Infusion of fresh frozen plasma, and in some cases protein C concentrate, was associated with clinical and biomarker improvement. This was notable with intra‐patient comparison of treated vs untreated courses. Use of endothelial barrier support therapy may reduce endothelial permeability by restoring both regulatory serum protein homeostasis and supporting the glycocalyx and is likely a critical component of care for this population.
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Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stem and progenitor cells (HSPCs) are critically dependent on a safe and effective strategy for ...cell procurement. We sought to assess the safety and efficacy of plerixafor when used in transfused patients with SCD for HSC mobilization. Six adult patients with SCD were recruited to receive a single dose of plerixafor, tested at lower than standard (180 µg/kg) and standard (240 µg/kg) doses, followed by CD34+ cell monitoring in peripheral blood and apheresis collection. The procedures were safe and well-tolerated. Mobilization was successful, with higher peripheral CD34+ cell counts in the standard vs the low-dose group. Among our 6 donors, we improved apheresis cell collection results by using a deep collection interface and starting apheresis within 4 hours after plerixafor administration. In the subjects who received a single standard dose of plerixafor and followed the optimized collection protocol, yields of up to 24.5 × 106 CD34+ cells/kg were achieved. Interestingly, the collected CD34+ cells were enriched in immunophenotypically defined long-term HSCs and early progenitors. Thus, we demonstrate that plerixafor can be employed safely in patients with SCD to obtain sufficient HSCs for potential use in gene therapy.
•Plerixafor was administered to 6 red cell exchange transfused adults with SCD without complications.•Sufficient numbers of peripheral blood CD34+ cells could be collected by apheresis for potential use in gene therapy manufacturing.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Prasugrel for Sickle Cell Vaso-Occlusive Events Badawy, Sherif M; Heeney, Matthew M; Hoppe, Carolyn C ...
The New England journal of medicine,
07/2016, Volume:
375, Issue:
2
Journal Article
Peer reviewed
To the Editor:
Heeney et al. (Feb. 18 issue)
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report the final results of the Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) trial, a phase 3 double-blind, ...placebo-controlled, parallel-group, multinational trial that evaluated the efficacy of prasugrel in reducing the rate of pain and acute chest episodes among children and adolescents with sickle cell disease. Although the trial did not show significant benefits of using prasugrel, it is one of the few trials involving patients with sickle cell disease that included patients from 13 countries and was successfully completed. Most other multinational studies included fewer countries.
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I . . .
Pyruvate kinase deficiency (PKD) is the most frequent red blood cell enzyme abnormality of the glycolytic pathway and the most common cause of hereditary nonspherocytic hemolytic anemia. Over 250 ...PKLR‐gene mutations have been described, including missense/nonsense, splicing and regulatory mutations, small insertions, small and gross deletions, causing PKD and hemolytic anemia of variable severity. Alu retrotransposons are the most abundant mobile DNA sequences in the human genome, contributing to almost 11% of its mass. Alu insertions have been associated with a number of human diseases either by disrupting a coding region or a splice signal. Here, we report on two unrelated Middle Eastern patients, both born from consanguineous parents, with transfusion‐dependent hemolytic anemia, where sequence analysis revealed a homozygous insertion of AluYb9 within exon 6 of the PKLR gene, causing precipitous decrease of PKLR RNA levels. This Alu element insertion consists a previously unrecognized mechanism underlying pathogenesis of PKD.
A pathogenic PKLR gene mutation from an Alu element insertion was identified in two unrelated families from Middle East, implicating the possibility of a founder insertion event in the Arab population, as a novel cause of pyruvate kinase deficiency. Both patients were born from consanguineous parents and presented with transfusion‐dependent hemolytic anemia. Sequence analysis revealed a homozygous insertion of AluYb9 within exon 6 of PKLR, leading to premature termination of the mutant transcript and precipitous decrease of PKLR RNA levels.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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