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Making Advances Against Sickle Cell Disease
As September — Sickle Cell Awareness Month — comes to a close, we take this opportunity to reflect on how much must be done to help patients in need and educate others on sickle cell disease — and also to recognize progress and hope for a better future.
In July, FDA approved Endari (L-glutamine oral powder) to reduce the severe complications from the blood disorder in patients age 5 years and older. Endari is only the second FDA-approved treatment for this disorder and the first since hydroxyurea was approved nearly 20 years ago. Studies showed that patients taking Endari experienced fewer trips to the emergency room and fewer hospitalizations for sickle cell pain than those given a placebo. They also had fewer occurrences of acute chest syndrome. Common side effects include constipation, nausea, headache, abdominal pain, cough, pain in the extremities, back pain, and chest pain.
FDA works with all interested in improving the lives of patients with sickle cell disease. In February 2014, we held the first ever federal meeting with patients as part of our Patient Focused Drug Development program. A highlight was learning what symptoms bothered patients the most in their daily lives – the sort of information that can help inform the development and use of patient reported outcomes. And for the past several years, clinical review staff has organized meetings to facilitate drug development in sickle cell disease. During these events, academic researchers, clinicians and FDA engaged in an interactive discussion on trial design, potential endpoints, and patient reported outcomes.
How schools can support pupils with sickle cell disease
As Sickle Cell Awareness Month (September) draws to a close, school leaders need to understand how the condition can affect pupils at school, and make sure that their policies are offering the right support
Sickle cell disease (SCD) is one of the most common genetic conditions in the world. It affects around one in 2,000 of all babies born in England.
People with SCD produce unusually shaped red blood cells. They can cause problems because they do not live as long as healthy blood cells and they become stuck in blood vessels. The disorder can cause episodes of severe pain known as “crises” which can require hospital treatment and can even cause death without the right care.
SCD may have a disruptive influence on the educational needs of a school child. Teachers may not always be aware that a child has it or not know how to support the child.
Dr Lola Oni, a senior specialist nurse consultant at Brent Sickle Cell and Thalassaemia Centre, says school leaders need be educated about the condition as “many children hide that they are in a crisis.”
“Teachers care about the wellbeing of their pupils. However, if they don’t know about sickle cell then they won’t be empathetic and can’t understand why a child is ill.
“If the child can’t walk or is having trouble lifting their arms and the teacher isn’t aware of the SCD then they might assume the child is being difficult for not wanting to go outside.”
However, Simon Dyson, a professor of applied sociology at De Montfort University with a lifelong interest in studying the social dimensions of SCD, believes that the responsibility for improving support for children with SCD should not lie with classroom teachers, but with those who devise school policies.
“My advice is that although teachers do need to know some basics about sickle cell, the key lies at the level of school policy, not at the level of raising awareness with individual teachers,” he says.
What he proposes is a “policy-based approach that recognises teachers are overwhelmed and that what is needed is a change in the social environment of the school that supports young people with SCD ‘in the background’, rather than relying on teachers remembering details of SCD.”
To help with this, Dyson and his team have produced a Guide to School Policy on Sickle Cell, which you can download from Tes.
And if you know that a child in your school has SCD, these tips from the Sickle Cell Society will help you to put in place the support they need.
Ensure the pupil is well hydrated to reduce the likelihood of becoming ill. Do not restrict drinking water in class. Any shared water fountain should be cleaned regularly to reduce the risk of infection.
- Toilet breaks
People with SCD cannot concentrate urine readily, therefore they produce large quantities of dilute urine and need to go toilet more often. Allow frequent toilet breaks.
People with SCD may experience severe anemia and may feel tired or lethargic and unable to concentrate in class. It is important for teachers to not mistake this as laziness. Climbing the stairs or walking between classes can tire them out. Encourage them to rest as much as possible. In some cases, it may be appropriate for the school to issue the child with a personal lift.
- Physical exercise
Children with SCD may lack the energy to do sporting activities or be experiencing joint pain. As a result, they should not be pushed beyond their limits and forced to do activities in the cold, wet or hot weather that could precipitate a sickle cell crisis. Listen to the child to understand the safe limits of physical exercise and follow advice from specialist medical teams.
Young people with SCD are advised not to become cold. Schools should work with the young person to establish agreed warmer clothing for indoor use. Make sure they are not sat next to a window or made to go outside in cold, rainy or windy weather during breaks.
If you are concerned about a pupil’s wellbeing, then you can seek advice from the following organisations:
The Sickle Cell Society
Organisation for Sickle Cell Anaemia Research
Sickle Cell Young Stroke Survivors
National Health Sickle Cell and Thalassaemia Service Screening Programme
TLC’s Tionne ‘T-Boz’ Watkins on her new book and living with sickle cell disease
Singer Tionne “T-Boz” Watkins is opening up about her battle with an incurable disease and how it affected her singing career as a member of the pop group TLC.
Watkins’ new memoir – book, “A Sick Life: TLC ‘n Me: Stories from On and Off the Stage,” describes how she has been able to overcome the difficulties of living with sickle cell disease.
“The title means so much for me,” Watkins told Robin Roberts in an exclusive interview on “GMA.” “It’s a strong word, ‘a sick life,’ ’cause I’ve had it all. I was told I would never live past 30; I would be disabled my whole life and never have kids.”
“But, no. Like I’ve traveled the world in TLC. I’ve worked with Michael Jackson,” the singer continued.
Watkins, Lisa “Left Eye” Lopes and Rozanda “Chilli” Thomas were at the top of the music charts in the 90s, and the trio is the second-highest selling girl group in the U.S., according to the Recording Industry Association of America (RIAA.)
The combination of hip-hop, R&B and pop made the band’s sound unique, but it was their powerful lyrics that resonated deeply with their audience.
“We talk about things that everybody can relate to. But we just do it in a fun way that you can dance to. And it’s not like we’re preaching, but it’s like you get the message that we’re in this together,” Watkins said.
Their hit song “Waterfalls” paid tribute to the AIDS epidemic, while other hits like “No Scrubs” had a much more straight forward message.
When asked to define “a scrub,” Watkins simply recited the famous lyrics: “A guy who can’t get no love from me, because he’s sitting on the passenger side pretending to have things he doesn’t have.”
“It’s like, ‘Dude, it’s not even your car,'” she said of the brutally honest lyric.
Performing and touring while dealing with sickle cell disease, which affects nearly 100,000 Americans according to the National Institute of Health, created one of the biggest challenges of Watkins’ life.
“The easiest way to describe it is oxygen isn’t getting to our vital organs,” Watkins described of the condition. “So, if it’s your legs, you can’t walk. Your arms, you can’t even hold a pencil and write … I went through so much.”
She said her rigorous schedule caused her to spend months in the hospital recovering.
New RFP Announcement: Sickle Cell Disease Association of America, Inc. (SCDAA)
Request for Proposal: SCDAA-HRSA Newborn Screening Follow-up Program
The Sickle Cell Disease Association of America, Inc. (SCDAA) is seeking to provide support for up to 17 Sickle Cell Disease Community Based Organizations (CBO’s) to work with state collaborators that will improve the care and reduce the number of individuals with sickle cell disease (SCD) who are “lost to follow-up” by supporting efforts of sickle cell disease education and service coordination. This program will ensure that individuals diagnosed with sickle cell disease receive appropriate follow-up services including counseling, education, access to a medical home, and other support services. This effort will be overseen by SCDAA as the National Coordinating Center.
RFP Release Date: October 1, 2017
Webinar/Teleconference: Tuesday, October 10, 2017
A pre-submission technical assistance webinar for all prospective applicants will be held:
- Time: 2:00 p.m. EST – 4:00 p.m. EST
- Dial In: 1-240-454-0879
- Passcode: 662 468 533
- Web Link:
Proposal Due Date: November 13, 2017, by 11:59 p.m. EST
CONTACT: Sonya Ross, Project Director ● PHONE: 410-528-1555 ● 800-421-8453
Articles in the Medical Literature
Blood Cells Mol Dis. 2017 Sep 21. pii: S1079-9796(17)30330-3. doi: 10.1016/j.bcmd.2017.09.006. [Epub ahead of print]
Sickle cell nephropathy begins with hyperfiltration and microalbuminuria and may progress to renal failure. The aim of this study was to determine the effects of losartan on glomerular function and albumin excretion in sickle cell anemia (SCA). Individuals with SCA on hydroxyurea with persistent albuminuria were enrolled in a 1-year study of losartan. Glomerular filtration rate (GFR) measured by iohexol clearance, albumin excretion rate (AER), and fractional clearance of dextran were assessed at baseline, short-term (1-2month), and long-term (≥12month) intervals. Twelve subjects (6 microalbuminuria, 6 macroalbuminuria) completed short-term studies; 8 completed long-term studies. Baseline GFR was 112ml/min/1.73m2 (71-147ml/min/1.73m2). AER decreased significantly at the short-term (median decrease -134 mcg/min, p=0.0063). GFR was not significantly-different at short-term or long-term intervals. Dextran clearance improved for diameters smaller than albumin (<36Å) but not larger sizes. Losartan therapy for ≥1year in sickle nephropathy results in lower albumin excretion with stable GFR. Filtration of neutral molecules ≥36Å was not changed by losartan, suggesting that the effect of losartan is a mechanism other than alteration of glomerular filtration size-selectivity.
Copyright © 2017 Elsevier Inc. All rights reserved.
Pediatr Blood Cancer. 2017 Sep 25. doi: 10.1002/pbc.26829. [Epub ahead of print]
Sickle cell disease (SCD) and hydroxyurea have implications for fertility and reproductive health. The goal of this study was to examine desire for parenthood and reproductive health knowledge among a cohort of adolescent and young adult (AYA) with SCD receiving hydroxyurea and their caregivers at a large pediatric academic center.
Patients with SCD were approached from September 2016 to July 2017 if they were: (1) 12-20 years old, (2) prescribed hydroxyurea for at least 6 months, (3) proficient in English, and (4) accompanied by a caregiver who was proficient in English and willing to participate. Participants self-reported sociodemographic characteristics and completed surveys to assess their/their child’s desire for parenthood and other life goals, and reproductive health knowledge.
Eighteen patient-caregiver dyads completed the study (78.3% of those eligible); 61.1% indicated that they wanted to have future biological children. Few participants reported receiving information about fertility (16.7% of AYA and 27.8% of caregivers) or birth control (11.1% of AYA and 22.2% of caregivers) from their/their child’s health care provider, and the majority had received no information on these topics. Less than half of participants reported that SCD (22.2% of AYA and 50.0% of caregivers) or hydroxyurea (11.1% of AYA and 27.8% of parents) could potentially impair fertility.
Biological parenthood was important to this cohort yet fertility and reproductive health knowledge was low, suggesting that clinicians should prioritize conversations about infertility risk and birth control options with AYA with SCD on hydroxyurea and their caregivers. More research is needed to identify optimal approaches to these discussions.
© 2017 Wiley Periodicals, Inc.
J Pain. 2017 Sep 21. pii: S1526-5900(17)30701-0. doi: 10.1016/j.jpain.2017.08.010. [Epub ahead of print]
Chronic opioid therapy is a common treatment regimen for patients with sickle cell disease (SCD), a chronically painful recessive hemoglobinopathy. The collective risk profile of chronic opioid therapy necessitates an understanding of which pain-related factors, such as affect and pain catastrophizing, are associated with the ebbs and flows of opioid use in daily life, a topic that has received very little attention among patients with any type of chronically painful condition, including SCD. We therefore investigated the variability of day-to-day patterns of short and long-acting opioid use and their associations with pain and pain-related cognitive and affective processes in daily life among patients with SCD using a nightly electronic diary (N = 45). Opioid use was self-reported and converted into oral morphine equivalents for analysis, which was conducted with mixed effects modeling. Results indicated that greater pain and pain catastrophizing were associated with greater use of short- acting opioids, and negative affect was associated with greater use of long-acting opioids. Additionally, the association of pain and short-acting opioid use was moderated by pain catastrophizing, showing that opioid use was elevated when patients catastrophized about their pain, even if they reported low levels of pain. These findings suggest that monitoring pain-related cognitive and affective variables may be a useful approach to understanding risk for problematic opioid use in patients with daily pain.
The present study demonstrates that pain and pain-related cognitive and affective variables are associated with daily variation in prescription opioid use in sickle cell disease. The findings may have broad implications for tracking and defining risk for prescription opioid misuse in patients with daily pain.
Copyright © 2017. Published by Elsevier Inc.
Biol Blood Marrow Transplant. 2017 Sep 19. pii: S1083-8791(17)30694-8. doi: 10.1016/j.bbmt.2017.08.039. [Epub ahead of print]
Allogeneic stem cell transplantation (HCT) is curative in patients with severe sickle cell disease (SCD) but a significant number of patients lack a HLA-identical sibling or matched unrelated donor. Mismatched related (haploidentical) HCT with post-transplant cyclophosphamide (PTCY) allows expansion of the donor pool but is complicated by high rates of graft failure. In this report, we describe a favorable haploidentical HCT approach in a limited cohort of sickle cell patients with significant co-morbidities. To reduce the risk of graft failure we administered the conditioning regimen of rabbit anti-thymocyte globulin (ATG), busulfan (BU) and fludarabine (FLU) preceded with two courses of pre-transplant immunosuppressive therapy (PTIS) with FLU and dexamethasone (DEX). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCY on days +3 and +4 followed by tacrolimus and mycophenolate mofetil (MMF) starting on day +5. Four patients (ages 13, 19, 19 and 23 years) received T-cell replete haploidentical stem cell infusion. All patients engrafted with 99.9-100% donor chimerism and all patients continue with stable engraftment at the last follow up (5 – 11 months post-transplant). Time to neutrophil engraftment was 14-26 days. Two patients had high levels of donor specific anti-HLA antibodies (DSA), which required the implementation of an antibody management protocol. This facilitated neutrophil engraftment on day +16 and day +26 respectively. One patient developed grade 1 acute GVHD which resolved. 3 patients developed mild, limited skin GVHD which responded to conventional immunosuppressive therapy. Human herpes virus 6 (HHV6) viremia was detected in three patients but resolved without treatment. One patient developed asymptomatic Cytomegalovirus (CMV) viremia which responded appropriately to standard therapy with ganciclovir. The prompt, stable engraftment and low toxicity in the post-transplant period makes PTIS with haploidentical transplant a promising option for the patients with SCD.
Copyright © 2017. Published by Elsevier Inc.
BMC Hematol. 2017 Sep 15;17:15. doi: 10.1186/s12878-017-0087-7. eCollection 2017.
In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes.
We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the βS-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (-α3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes.
Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients.
Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.
PMCID: PMC5602866 Free PMC Article
Blood. 2017 Sep 20. pii: blood-2016-12-755777. doi: 10.1182/blood-2016-12-755777. [Epub ahead of print]
Dubert M1, Elion J2, Tolo A3, Diallo DA4, Diop S5, Diagne I6, Sanogo I3, Belinga S7, Guifo O8, Wamba G9, Ngo Sack F10, Boidy K3, Kamara I3, Traore Y4, Diakite CO11, Gbonon V12, Faye BF5, Seck M5, Deme Ly I6, Chelo D13, N’Guetta R14, Diop IB15, Gaye B16, Jouven X17, Ranque B18.
The hyperhemolysis paradigm that describes overlapping “hyperhemolytic-endothelial dysfunction” and “high hemoglobin-hyperviscous” subphenotypes of sickle cell disease (SCD) patients is based on North American studies. We performed a transversal study nested in the CADRE cohort to analyze the association between steady-state hemolysis and vascular complications of SCD among sub-Saharan African patients. In Mali, Cameroon, and Ivory Coast, 2,407 SCD patients (1,751 SS-Sβ0, 495 SC and 161 Sβ+), aged three years old and over, were included at steady-state. Relative hemolytic intensity was estimated from a composite index derived from principal component analysis, which included bilirubin levels or clinical icterus, and lactate dehydrogenase levels. We assessed vascular complications (elevated tricuspid regurgitant jet velocity (TRV), microalbuminuria, leg ulcers, priapism, stroke, and osteonecrosis) by clinical examination, laboratory tests, and echocardiography. After adjustment for age, sex, country, and SCD phenotype, a low hemoglobin level was significantly associated with TRV and microalbuminuria in the whole population and with leg ulcers in SS-Sβ0 adults. A high hemolysis index was associated with microalbuminuria in the whole population and with elevated TRV, microalbuminuria, and leg ulcers in SS-Sβ0 adults, but these associations were no longer significant after adjustment for hemoglobin level. In conclusion, severe anemia at steady-state in SCD patients living in West and Central Africa is associated with elevated TRV, microalbuminuria, and leg ulcers, but these vascular complications are not independently associated with indirect markers of increased hemolysis. Other mechanisms leading to anemia, including malnutrition and infectious diseases, may also play a role in the development of SCD vasculopathy.
Copyright © 2017 American Society of Hematology.
Cochrane Database Syst Rev. 2017 Sep 19;9:CD004198. doi: 10.1002/14651858.CD004198.pub3. [Epub ahead of print]
Sickle cell disease comprises a group of genetic haemoglobin disorders. The predominant symptom associated with sickle cell disease is pain resulting from the occlusion of small blood vessels by abnormally ‘sickle-shaped’ red blood cells. There are other complications, including chronic organ damage and prolonged painful erection of the penis, known as priapism. Severity of sickle cell disease is variable, and treatment is usually symptomatic. Priapism affects up to half of all men with sickle cell disease, however, there is no consistency in treatment. We therefore need to know the best way of treating this complication in order to offer an effective interventional approach to all affected individuals.
To assess the benefits and risks of different treatments for stuttering (repeated short episodes) and fulminant (lasting for six hours or more) priapism in sickle cell disease.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched trial registries.Date of the most recent search of the Group’s Haemoglobinopathies Trials Register: 15 September 2017.Date of most recent search of trial registries and of Embase: 12 December 2016.
All randomised or quasi-randomised controlled trials comparing non-surgical or surgical treatment with placebo or no treatment, or with another intervention for stuttering or fulminant priapism.
DATA COLLECTION AND ANALYSIS:
The authors independently extracted data and assessed the risk of bias of the trials.
Three trials with 102 participants were identified and met the criteria for inclusion in this review. These trials compared stilboestrol to placebo, sildenafil to placebo and ephedrine or etilefrine to placebo and ranged in duration from two weeks to six months. All of the trials were conducted in an outpatient setting in Jamaica, Nigeria and the UK. None of the trials measured our first primary outcome, detumescence but all three trials reported on the reduction in frequency of stuttering priapism, our second primary outcome. No significant effect of any of the treatments was seen compared to placebo. Immediate side effects were not found to be significantly different from placebo in the two trials where this information was reported. We considered the quality of evidence to be low to very low as all of the trials were at risk of bias and all had low participant numbers.
There is a lack of evidence for the benefits or risks of the different treatments for both stuttering and fulminant priapism in sickle cell disease. This systematic review has clearly identified the need for well-designed, adequately-powered, multicentre randomised controlled trials assessing the effectiveness of specific interventions for priapism in sickle cell disease.
Am J Hematol. 2017 Sep 19. doi: 10.1002/ajh.24908. [Epub ahead of print]
Narbey D1,2,3, Habibi A2,3,4, Chadebech P1,2,3, Mekontso-Dessap A5,6,7, Khellaf M7,8, Lelièvre JD7,9, Godeau B5,10, Michel M7,10, Galactéros F2,3,4,7, Djoudi R1, Bartolucci P2,3,4,7, Pirenne F1,2,3,7.
Delayed hemolytic transfusion reaction (DHTR) is a life-threatening complication of transfusion in sickle cell disease (SCD). The frequency of DHTR is underestimated because its symptoms mimic those of vaso-occlusive crisis and antibodies (Abs) are often not detectable. No predictive factors for identifying patients likely to develop DHTR have yet been defined. We conducted a prospective single-center observational study over 30 months in adult sickle cell patients. We included 694 transfusion episodes (TEs) in 311 patients, divided into occasional TEs (OTEs: 360) and chronic transfusion program (CTEs: 334). During follow-up, 15 cases of DHTR were recorded, exclusively after OTEs. DHTR incidence was 4.2% per OTE (95% CI [2.6; 6.9]) and 6.8% per patient during the 30 months of the study (95% CI [4.2; 11.3]). We studied 11 additional DHTR cases, to construct a predictive score for DHTR. The DHTR mortality is high, 3 (11.5%) of the 26 DHTR patients died. The variables retained in the multivariate model were history of DHTR, number of units previously transfused and immunization status before transfusion. The resulting DHTR-predictive score had an area under the ROC curve of 0.850 [95% CI: 0.780-0.930], a negative-predictive value of 98.4% and a positive-predictive value of 50%. We report in our study population, for the first time, the incidence of DHTR, and, its occurrence exclusively in occasionally transfused patients. We also describe a simple score for predicting DHTR in patients undergoing occasional transfusion, to facilitate the management of blood transfusion in SCD patients. This article is protected by copyright. All rights reserved.
© 2017 Wiley Periodicals, Inc.
J Multidiscip Healthc. 2017 Aug 30;10:335-346. doi: 10.2147/JMDH.S90630. eCollection 2017.
Sickle cell retinopathy (SCR) is the most representative ophthalmologic complication of sickle cell disease (SCD), a hemoglobinopathy affecting both adults and children. SCR presents a wide spectrum of manifestations and may even lead to irreversible vision loss if not properly diagnosed and treated at the earliest. Over the past decade, multidisciplinary research developments have focused upon systemic, genetic, and ocular risk factors of SCR, enabling the clinician to better diagnose and manage these patients. In addition, newer imaging and testing modalities, such as spectral domain-optical coherence tomography angiography, have resulted in the detection of subclinical retinopathy related to SCD. Innovative therapy includes intravitreal injection of an anti-vascular endothelial growth factor (eg, Lucentis® [ranibizumab] or Eylea® [aflibercept]) which appears comparatively safe and efficient, and may be combined with laser photocoagulation (LPC) for proliferative SCR. The effect of LPC alone does not significantly lead to the regression of advanced SCR, although it helps in avoiding hemorrhage and sight loss. This comprehensive article is based on 10-years retrospective (2007-2017) studies. It aims to present advances and recommendations in SCR theranostics while pointing out the requirement of combinatorial approaches for better management of SCR patients. To reach this goal, we identified and analyzed randomized original and review articles, clinical trials, non-randomized intervention studies, and observational studies using specified keywords in various databases (eg, Medline, Embase, Cochrane, ClinicalTrials.gov).
PMCID: PMC5587171 Free PMC Article
Conflict of interest statement
Disclosure The authors report no conflicts of interest in this work.
Am J Hematol. 2017 Sep 14. doi: 10.1002/ajh.24906. [Epub ahead of print]
Hydroxyurea has proven clinical benefits and is recommended to be offered to all children with sickle cell anemia (SCA), but the optimal dosing regimen remains controversial. Induction of red blood cell fetal hemoglobin (HbF) by hydroxyurea appears to be dose-dependent. However, it is unknown whether maximizing HbF% improves clinical outcomes. HUSTLE (NCT00305175) is a prospective observational study with a primary goal of describing the long-term clinical effects of hydroxyurea escalated to maximal tolerated dose (MTD) in children with SCA. In 230 children, providing 610 patient-years of follow up, the mean attained HbF% at MTD was >20% for up to 4 years of follow-up. When HbF% values were ≤20%, children had twice the odds of hospitalization for any reason (P < .0001), including vaso-occlusive pain (P < .01) and acute chest syndrome (ACS) (P < .01), and more than four times the odds of admission for fever (P < .001). Thirty day readmission rates were not affected by HbF%. Neutropenia (ANC <1000 × 106 /L) was rare (2.3% of all laboratory monitoring), transient, and benign. Therefore, attaining HbF >20% was associated with fewer hospitalizations without significant toxicity. These data support the use of hydroxyurea in children, and suggest that the preferred dosing strategy is one that targets a HbF endpoint >20%.
© 2017 Wiley Periodicals, Inc.
Expert Rev Hematol. 2017 Sep 23:1-8. doi: 10.1080/17474086.2017.1379895. [Epub ahead of print]
Sickle cell disease (SCD) is one of the most common hemoglobinopathy, affecting a considerable proportion of black populations of African origin, Middle East and in the Indian sub-continent. Women with SCD are more likely to experience adverse pregnancy and delivery outcomes. Hypertensive diseases in pregnancy such as preeclampsia and eclampsia are more common in women with sickle cell disease. Areas covered: This review examined the influence of hypertension and SCD in pregnancy, and provides the preliminary evidence that the traditional systolic and diastolic blood pressure thresholds for hypertensive disorders such as pre-eclampsia and eclampsia may require reassessment in pregnant women with SCD. The causes of maternal and perinatal morbidity and mortality, hypertensive complications of pregnancy in women with and without sickle cell disease were reviewed. A MEDLINE database search using medical subject headings (MeSH) and keywords for articles regarding sickle cell disease, pregnancy and hypertension was performed. Expert commentary: Pregnancy in women with sickle cell disease is associated with high maternal and perinatal morbidity and mortality. Using the existing thresholds for diagnosis and treatment for hypertensive disease in pregnancy without adjustment to accommodate for the lower systolic and diastolic blood pressure in those with sickle cell disease may worsen an already poor maternal and perinatal outcome in this population.
JAMA Pediatr. 2017 Sep 11. doi: 10.1001/jamapediatrics.2017.2526. [Epub ahead of print]
Acute chest syndrome (ACS) is a common, serious complication of sickle cell disease (SCD) and a leading cause of hospitalization and death in both children and adults with SCD. Little is known about the effectiveness of guideline-recommended antibiotic regimens for the care of children hospitalized with ACS.
To use a large, national database to describe patterns of antibiotic use for children with SCD hospitalized for ACS and to determine whether receipt of guideline-adherent antibiotics was associated with lower readmission rates.
Design, Setting, and Participants:
Retrospective cohort study including 14 480 hospitalizations in 7178 children (age 0-22 years) with a discharge diagnosis of SCD and either ACS or pneumonia. Information was obtained from 41 children’s hospitals submitting data to the Pediatric Health Information System from January 1, 2010, to December 31, 2016.
National Heart, Lung, and Blood Institute guideline-adherent (macrolide with parenteral cephalosporin) vs non-guideline-adherent antibiotic regimens.
Main Outcomes and Measures:
Acute chest syndrome-related and all-cause 7- and 30-day readmissions.
Of the 14 480 hospitalizations, 6562 (45.3%) were in girls; median (interquartile range) age was 9 (4-14) years. Guideline-adherent antibiotics were provided in 10 654 of 14 480 hospitalizations for ACS (73.6%). Hospitalizations were most likely to include guideline-adherent antibiotics for children aged 5 to 9 years (3230 of 4047 [79.8%]) and declined to the lowest level for children 19 to 22 years (697 of 1088 [64.1%]). Between-hospital variation in antibiotic regimens was wide, with use of guideline-adherent antibiotics ranging from 24% to 90%. Children treated with guideline-adherent antibiotics had lower 30-day ACS-related (odds ratio [OR], 0.71; 95% CI, 0.50-1.00) and all-cause (OR, 0.50; 95% CI, 0.39-0.64) readmission rates vs children who received other regimens (cephalosporin and macrolide vs neither drug class).
Conclusions and Relevance:
Current approaches to antibiotic treatment in children with ACS vary widely, but guideline-adherent therapy appears to result in fewer readmissions compared with non-guideline-adherent therapy. Efforts to increase the dissemination and implementation of SCD treatment guidelines are warranted as is comparative effectiveness research to strengthen the underlying evidence base.
Thromb Res. 2017 Sep 6;158:113-120. doi: 10.1016/j.thromres.2017.08.020. [Epub ahead of print]
Previous studies have suggested a chronic hypercoagulable state in SCD, and that thrombosis also plays a role in the pathophysiology of sickle cell vaso-occlusive pain crises (VOC). Studies looking at thrombin generation have produced conflicting results. In this study we aimed to assess and compare whole blood thromboelastography (TEG) and plasma Calibrated Automated Thrombogram (CAT) in SCD versus healthy controls and in four different SCD subgroups.
MATERIALS AND METHODS:
In this prospective observational study, TEG and 1pM TF activated CAT assays were performed in citrated blood samples from 77 adult (18-66years old) SCD patients (HbSS and HbSB) and 22 healthy (HbAA) ethnically-matched controls.
RESULTS AND CONCLUSIONS:
SCD was associated with a prothrombotic state in all TEG parameters. CAT results showed that the upslope of the CAT in SCD displayed a hypercoagulable state with shorter time to peak and higher velocity index, but the downslope was also faster leading to an overall lower endogenous thrombin potential (ETP) compared to healthy controls. TEG subgroup analyses showed that during VOC the prothrombotic state is greater compared to patients on disease ameliorating therapy. CAT did not display statistically significant differences between the SCD subgroups. This study shows that the prothrombotic state in SCD is best displayed with TEG, and suggests the hypercoagulable changes of SCD rely at least in part in the cellular components of blood, which can only be detected in whole blood assays.
Copyright © 2017 Elsevier Ltd. All rights reserved.
J Pediatr Nurs. 2017 Sep – Oct;36:191-196. doi: 10.1016/j.pedn.2017.05.012. Epub 2017 Jul 7.
To evaluate health literacy in a cohort of 75 adolescents with sickle cell disease (SCD).
DESIGN AND METHODS:
This cross-sectional, descriptive correlational study included assessment of demographic measures and appraisal of data resulting from completion of the REALM-Teen and Newest Vital Sign (NVS) instruments by 75 Black, non-Hispanic adolescents with SCD. Convenience sampling was utilized. Inclusion criteria were a diagnosis of one of the four primary genotypes of SCD and age 10-19years.
Thirty-seven males and 38 females were recruited for the study. Their mean age was 14.7years (SD=2.2; range 8.1). Their grade level ranged from 4 to 12 (mean 8.7; SD=2.2). Scores on the REALM-Teen ranged from 12 to 66 (mean 53.7; SD=12.8). Scores on the NVS ranged from 0 to 6 (mean 2.37; SD=1.33). These health literacy scores were lower using both the REALM-Teen and the NVS instruments when compared to scores in all healthy adolescents and adults. Current grade level and health literacy scores showed a moderately high positive correlation (r=0.52, p<0.01). Health literacy scores were also significantly positively correlated with age (r=0.49, p<0.01) and income (r=0.37, p<0.01).
Health literacy in adolescents with SCD is suboptimal. Future research should include identifying facilitators and barriers to health literacy levels in a larger cohort of adolescents with SCD.
Health literacy is a potential facilitator of successful health outcomes for all adolescents. This study lays a solid foundation for future adolescent health literacy initiatives.
Copyright © 2017 Elsevier Inc. All rights reserved.
Biol Blood Marrow Transplant. 2017 Sep 4. pii: S1083-8791(17)30693-6. doi: 10.1016/j.bbmt.2017.08.038. [Epub ahead of print]
Abraham A1, Hsieh M2, Eapen M3, Fitzhugh C2, Carreras J4, Keesler D4, Guilcher G5, Kamani N6, Walters MC7, Boelens JJ8, Tisdale J2, Shenoy S9; National Institutes of Health; Center for International Blood and Marrow Transplant Research.
Mixed donor chimerism after hematopoietic cell transplantation for sickle cell disease (SCD) can result in resolution of disease symptoms, but symptoms recur when donor chimerism is critically low. The relationship between chimerism, hemoglobin S (HbS) level, and symptomatic disease was correlated retrospectively in 95 patients who had chimerism reports available at day 100 and at 1 and 2 years after transplantation. Recurrent disease was defined as recurrence of vaso-occlusive crises, acute chest syndrome, stroke, and/or HbS levels > 50%. Thirty-five patients maintained full donor chimerism (myeloid or whole blood) through 2 years. Donor chimerism was less than 10% (defined as graft failure) in 13 patients during this period. Mixed chimerism was reported in the remaining 47 patients (range, 10% to 94%). The lowest documented donor chimerism without symptomatic disease was 26%. Of 12 surviving patients with recurrent disease, 2 had recurrence of symptoms before documented graft failure (donor chimerism of 11% and 17%, respectively). Three patients underwent second transplantation for graft failure. None received donor leukocyte infusion to maintain mixed chimerism or prevent graft failure. We conclude stable donor chimerism greater than 25% is associated with resolution of SCD-related symptoms, and HbS level of 50% or higher is predictive of recurrent disease.
Copyright © 2017. Published by Elsevier Inc.
Sickle Cell Conferences and Events
Living Well with Sickle Cell
Please join the sickle cell team at Children’s National Medical Center for our 8th Annual Family Education Symposium: Living Well with Sickle Cell. All are welcome to this free event!
Saturday November 4th, 2017
Sheikh Zayed Campus for Advanced Children’s Medicine
Children’s National Health System
111 Michigan Ave NW
2nd Floor, Auditorium
Washington, DC 20010
We will have a speaker from Shady Grove Fertility to discuss pre-implantation and sessions on topics including Bone Marrow Transplant, Hydroxyurea, Pain and the ongoing opioid crisis, social security, and transition to adult care. Breakfast will be served. Please register at: https://www.surveymonkey.com/r/5MYGT2L or call Alexandra Hollman, LICSW at 202-476-1333.
11th Annual Sickle Cell Disease and Thalassemia Conference
The 2017 Annual Scientific Conference on Sickle Cell and Thalassemia is a three-day conference aimed at all those with a common interest in sickle cell disease and thalassemia. It will be held in London on October 11-13, 2017. There will also be sessions on genetics and genomic progress, curative therapies and emerging services, as well as abstract and poster presentations. For more information and to register click here.
3RD ANNUAL SICKLE CELL DISEASE SYMPOSIUM
The Nuts and Bolts of Sickle Cell Disease Management
Hosted by Carolinas HealthCare System
Levine Cancer Institute
WHEN: Saturday, October 28,2017
7:30 a.m. to 4:30 p.m.
WHERE: Carolinas HealthCare System Northeast
920 Church Street, North
Concord, NC 28025
Carolinas HealthCare System Northeast designates this educational activity for a maximum of 6.75 AMA PRA Category I Credit(s) ™. Physicians should claim only credit commensurate with the extent of their participation in the activity.
1.25 Hours meet NCMB CME Requirement for Physician/PA Opioid Education
SCDAA 45th Annual National Convention on Sickle Cell Disease
With over 447 researchers, physicians, nurses, socials workers, individuals living with SCD & SCT and more we are excited to reunite with you again on October 25-28, 2017
The SCDAA Annual Convention is a four-day conference designed to address the multi-factorial aspects of Sickle Cell Disease. This year the event will be held in Atlanta, Georgia, a city near and dear to the sickle cell community! https://www.sicklecelldisease.org/2017/03/07/45th-annual-national-convention/
The 11th Sickle Cell in Focus Conference
26-27, October 2017 Kingston, Jamaica
We are pleased to announce that Sickle Cell in Focus (SCiF) will be held for the first time in Kingston, Jamaica on October 26-27, 2017. This year, SCiF will be co-hosted by the National Heart, Lung, and Blood Institute and the University of West Indies, Jamaica. SCiF is a two-day, intensive, educational update on sickle cell disease. This year’s conference will focus on the latest clinical trials, the science and mechanisms for new therapeutic targets, and curative therapies. This two-day intensive educational conferences includes both clinical and scientific lectures, aimed at clinicians, academics, and other healthcare professionals involved in sickle cell disease around the world. Contact Rusinel Amarante| firstname.lastname@example.org