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NIH launches initiative to accelerate genetic therapies to cure sickle cell disease
The National Institutes of Health announced the launch of a new initiative to help speed the development of cures for sickle cell disease, a group of inherited blood disorders affecting at least 100,000 people in the United States and 20 million worldwide. The Cure Sickle Cell Initiative will take advantage of the latest genetic discoveries and technological advances to move the most promising genetic-based curative therapies safely into clinical trials within five to 10 years.
“Our scientific investments have brought us to a point where we have many tools available to correct or compensate for the defective gene that causes sickle cell disease. We are now ready to use these tools to speed up our quest for a cure,” said Gary H. Gibbons, M.D., director of NIH’s National Heart, Lung, and Blood Institute (NHLBI), which is leading the effort.
Sickle cell disease results from a single genetic mutation that causes a person’s red blood cells to form an abnormal, sickle shape. These sickled cells can clog the blood vessels and deprive cells of oxygen. In turn, this lack of oxygen wreaks havoc on the body, damaging organs, causing severe pain, and potentially leading to premature death.
Decades of basic research on sickle cell disease have laid the groundwork for novel genetic approaches to cures, such as the genetic editing of bone marrow cells, which have shown great promise in animal models and in some small scale human studies. In addition, the NHLBI Production Assistance for Cellular Therapies (PACT) program(link is external) has been working with researchers to manufacture cellular therapeutic products, including genetically modified cells, that can be used safely in clinical trials with patients.
NIH spends approximately $100 million on sickle cell disease research each year. Through this initiative, NHLBI seeks to support the development of cell and genetic therapies resources, clinical trials, comparator analyses of different management strategies, data repositories and resources, and patient and advocate engagement activities related to curative therapies for this condition. Already in 2018, NHLBI committed an additional $7 million to jumpstart the initiative’s research and engagement infrastructure.
NHLBI has named hematologist Edward J. Benz Jr., M.D., President and CEO Emeritus of Dana-Farber Cancer Institute, as the Initiative’s executive director, and the Emmes Corporation, a contract research organization with specialized expertise in clinical trials, gene and cell therapy development in preclinical studies, as its coordinating center.
The initiative and its research partners will establish a national data warehouse of genetic therapies for sickle cell disease and conduct comparative analyses of therapeutic approaches to assess both clinical and cost effectiveness. They will also establish national networks to make it easier for patients and providers to learn and engage with the research, clinical trials, and other activities happening across the country.
“The engagement of patients will be a cornerstone of this effort,” said Benz. “Patients will work alongside researchers in developing and recruiting for clinical trials.”
Currently, the only cure for sickle cell disease is a bone marrow transplant, a procedure in which a sick patient receives bone marrow from a healthy, genetically-compatible sibling donor. However, transplants are too risky for many adults, and only about 18 percent of children with sickle cell disease have a healthy, matched sibling donor.
The Cure Sickle Cell Initiative seeks to develop cures for a far broader group of individuals with the disease, and it is initially focusing on gene therapies that modify the patient’s own hematopoietic stem cells (HSCs), which make red and other blood cells. These modified HSCs can then be given back to the patient via a bone marrow transplant, making a cure available to more patients who lack a matched donor.
“This initiative is giving patients, families, and communities a reason for hope. I’m particularly pleased that we are able to make this announcement during Sickle Cell Awareness month, when we are shining a spotlight on the toll of this devastating disease,” said ADM Brett Giroir, M.D. Assistant Secretary for Health at the U.S. Department of Health and Human Services (HHS).
This patient-focused Initiative builds on the legacy of NHLBI-supported research that has contributed to improving clinical care for patients who have sickle cell disease. It also complements the Institute’s broader sickle cell disease research investment, which includes basic, clinical, translational, and implementation science research.
New Book – A Doctor In A Patient’s Body; Dreaming Big with Sickle Cell Disease and Chronic Pain.” by Dr. Simone Eastman Uwan is an inspirational and motivational account of “thriving” with sickle cell disease. Dr. Uwan was born in Guyana, South America and grew up with her younger sister and mother until she was 13 years old when she and her family immigrated to the United States in 1984. She finished her undergraduate degree at Columbia University, her MD degree at Stanford University School of Medicine, and completed a Family Practice residency there. She has provided care for the underserved, working mostly in community clinics.
This book shows by example that people with chronic pain and a lifelong disease can still make a powerful impact if they follow their calling. To quote Dr. Uwan “I’m a Sickle Cell Thriver, not just a survivor!” “To survive is to remain alive where others have died. You don’t have to do much more than that. But YOU, you are productive and confident of a great life ahead of you, and ready to follow your dreams. You will have a legacy because you will choose to live and laugh and love the best way you know how”.
This book is a must read for all sickle cell patients, their family, friends and the medical providers who care for them.
Book Launch is November 1st 2018, noon-1pm EST(9-10am PST).Please keep the date in mind and come support my book’s launch party on Facebook!
Get your FREE digital copy of my book as a thank you for your support on that day! Your attendance to the launch party is important and will count towards gauging how well this book does. Many, many thanks. Simone Uwan M.D.
Articles in the Medical Literature
Pediatr Blood Cancer. 2018 Oct 21:e27503. doi: 10.1002/pbc.27503. [Epub ahead of print]
There are conflicting reports on the role of hydroxyurea (HU) in the pathogenesis of avascular necrosis of the femoral head (AVNFH) in patients with sickle cell disease (SCD).
The present study is a prospective cohort study of Kuwaiti children with SCD who were treated with HU. They had magnetic resonance imaging of the hips before starting HU and at regular intervals during a follow-up period, ranging from 1 to 15 years.
There were 40 patients (18 SS, 19 Sβ0-thalassemia, and three SD genotypes), aged 6-20 years. Pre-HU, 11 (27.5%) had varying grades of AVNFH, while post HU, the prevalence was 32.5%. Two patients developed new lesions during the study, while five (45.5%) that had lesions pre-HU remained static, another five (45.5%) progressed, and one (9%) improved radiologically. The older patients who had been on HU the longest were more likely to deteriorate. The only hematological parameter that was consistently associated with AVNFH was the reticulocyte count.
The frequency and rate of progression of AVNFH in this study is much less than that previously reported for our patients not treated with HU. There is no evidence that HU therapy is a risk factor for AVNFH. It may, in fact, prevent new lesions and deter the progression of existing AVNFH.
© 2018 Wiley Periodicals, Inc.
Nitric Oxide. 2018 Oct 18. pii: S1089-8603(18)30190-3. doi: 10.1016/j.niox.2018.10.003. [Epub ahead of print]
Hydroxyurea (HU) has been suggested to act as a nitric oxide (NO) donor in sickle cell anemia (SCA). However, little is known about the HU NO-related effects on red blood cell (RBC) physiology and NO signalling pathway. Thirty-four patients with SCA (22 under HU treatment (HU+) and 12 without (HU-)) and 17 healthy subjects (AA) were included. RBC nitrite content, deformability and reactive oxygen species (ROS) levels were measured. RBC NO-synthase (RBC-NOS) signalling pathway was assessed by the measurement of RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation. We also investigated the in vitro effects of Sodium Nitroprusside (SNP), a NO donor, on the same parameters in SCA RBC. RBC nitrite content was higher in HU + than in HU- and AA. RBC deformability was decreased in SCA patients compared to AA but the decrease was more pronounced in HU-. RBC ROS level was increased in SCA compared to AA but the level was higher in HU- than in HU+. RBC-NOS serine1177 and RBC-AKT serine473 phosphorylation were decreased in HU + compared to HU- and AA. SCA RBC treated with SNP showed increased deformability, reduced ROS content and a decrease in AKT and RBC-NOS phosphorylation. Our study suggests that HU, through its effects on foetal haemoglobin and possibly on NO delivery, would modulate RBC NO signalling pathway, RBC rheology and oxidative stress.
Health Qual Life Outcomes. 2018 Oct 19;16(1):203. doi: 10.1186/s12955-018-1030-8.
Families play a critical role in supporting the health and well-being of children with chronic illnesses, who face a lifetime of responsibility for self-management of their condition. Our goal was to investigate whether the novel Patient-Reported Outcomes Measurement Information System® (PROMIS®) Pediatric Family Relationships measure, developed primarily within the general pediatric population, reflects the experiences of family relationships for chronically ill children and their parents.
We conducted semi-structured qualitative interviews with children (aged 8-17) with common chronic conditions: asthma (n = 6), type 1 diabetes (n = 5), or sickle cell disease (n = 5), and separately with one of their parents (n = 16). Interviews were recorded, and two team members independently coded the written transcripts facilitated by Nvivo 10. The systematic content analysis used a combination of: 1) pre-specified themes corresponding to the six facets of the domain identified during measure development and reflected in the content of the items (i.e., Sense of Family; Love and Caring; Value and Acceptance; Trust, Dependability, and Support; Communication; Enjoyment), as well as 2) open-coding, allowing participants to define important concepts (i.e., disease impact).
Family relationships were conceptualized in a similar way to the general population, as evidenced by child and parent responses to open-ended questions about family relationships and to specific probes that corresponded with the item content in the Family Relationship 8-item short form. Children spontaneously discussed the impact of their disease on family relationships less often than parents did. Although participants described how living with a chronic illness positively and negatively impacted aspects of family relationships, nearly all participants believed their responses to the PROMIS® Family Relationships items would not change if they (or their child) did not have a chronic illness.
Among a sample of families of children with one of 3 chronic illnesses, participants described family relationships in a way that was consistent with the facets of the PROMIS® Family Relationship domain. This study adds to the content validity of the measure for children with chronic illness.
J Pediatr Hematol Oncol. 2018 Oct 18. doi: 10.1097/MPH.0000000000001341. [Epub ahead of print]
To examine the acceptability, feasibility, and efficacy of a health care portal.
Adolescents and young adults with sickle cell disease were taught how to use sickle cell disease conditions page in MyChart and completed questionnaires at baseline, postintervention (T2, 6 wk after baseline) and after 3 months (T3). In total, 44 participants (M age=18.82, SD=2.72) viewed an average of 58.07 pages from T1 to T2. The portal was highly accepted (90.32%). Efficacy data indicated that portal use was associated with improved patient-provider communication.
Electronic portals are promising tools for improving medical self-management.
Cochrane Database Syst Rev. 2018 Oct 19;10:CD003426. doi: 10.1002/14651858.CD003426.pub6. [Epub ahead of print]
Sickle cell disease is an inherited disorder of hemoglobin, resulting in abnormal red blood cells. These are rigid and may block blood vessels leading to acute painful crises and other complications. Recent research has focused on therapies to rehydrate the sickled cells by reducing the loss of water and ions from them. Little is known about the effectiveness and safety of such drugs. This is an updated version of a previously published review.
To assess the relative risks and benefits of drugs to rehydrate sickled red blood cells.
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group’s Haemoglobinopathies Trials Register. We also searched online trials registries for any ongoing trials (01 July 2018).Last search of the Group’s Haemoglobinopathies Trials Register: 08 October 2018.
Randomized or quasi-randomized controlled trials of drugs to rehydrate sickled red blood cells compared to placebo or an alternative treatment.
DATA COLLECTION AND ANALYSIS:
Both authors independently selected studies for inclusion, assessed study quality and extracted data.
Of the 51 studies identified, three met the inclusion criteria, including 524 people with sickle cell disease aged between 12 and 65 years of age. One study tested the effectiveness of zinc sulphate as compared to placebo and the remaining two assessed senicapoc versus placebo. No deaths were seen in any of the studies (low-quality evidence). The zinc sulphate study showed a significant reduction in painful crises (in a total of 145 participants) over one and a half years, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (moderate-quality evidence). However, analysis was restricted due to limited statistical data. Changes to red blood cell parameters and blood counts were inconsistent (very low-quality evidence). No serious adverse events were noted in the study. The Phase II dose-finding study of senicapoc (a Gardos channel blocker) compared to placebo showed that the high dose senicapoc showed significant improvement in change in hemoglobin level, the number and proportion of dense red blood cells, red blood cell count and indices and hematocrit value (very low-quality evidence). The results with low-dose senicapoc were similar to the high-dose senicapoc group but of lesser magnitude. There was no difference in the frequency of painful crises between the three groups (low-quality evidence). A subsequent Phase III study of senicapoc was terminated early since there was no difference observed between the treatment and control groups in the primary end point of painful crises.
While the results of zinc for reducing sickle-related crises are encouraging, larger and longer-term multicenter studies are needed to evaluate the effectiveness of this therapy for people with sickle cell disease.While the Phase II and the prematurely terminated phase III studies of senicapoc showed that the drug improved red blood cell survival (depending on dose), this did not lead to fewer painful crises.Given this is no longer an active area of research, this review will no longer be regularly updated.
Br J Haematol. 2018 Oct 18. doi: 10.1111/bjh.15600. [Epub ahead of print]
Lobitz S1,2, Telfer P3, Cela E4, Allaf B5, Angastiniotis M6, Backman Johansson C7, Badens C8, Bento C9, Bouva MJ10, Canatan D11, Charlton M12, Coppinger C12, Daniel Y12, de Montalembert M13, Ducoroy P14, Dulin E4, Fingerhut R15, Frömmel C16, García-Morin M4, Gulbis B17, Holtkamp U18, Inusa B19, James J20, Kleanthous M21, Klein J22, Kunz JB23, Langabeer L24, Lapouméroulie C25, Marcao A26, Marín Soria JL27, McMahon C24, Ohene-Frempong K28, Périni JM29, Piel FB30, Russo G31, Sainati L32, Schmugge M33, Streetly A34,35, Tshilolo L36, Turner C37, Venturelli D38, Vilarinho L26, Yahyaoui R39, Elion J25, Colombatti R32; with the endorsement of EuroBloodNet, the European Reference Network in Rare Haematological Diseases.
Sickle Cell Disease (SCD) is an increasing global health problem and presents significant challenges to European health care systems. Newborn screening (NBS) for SCD enables early initiation of preventive measures and has contributed to a reduction in childhood mortality from SCD. Policies and methodologies for NBS vary in different countries, and this might have consequences for the quality of care and clinical outcomes for SCD across Europe. A two-day Pan-European consensus conference was held in Berlin in April 2017 in order to appraise the current status of NBS for SCD and to develop consensus-based statements on indications and methodology for NBS for SCD in Europe. More than 50 SCD experts from 13 European countries participated in the conference. This paper aims to summarise the discussions and present consensus recommendations which can be used to support the development of NBS programmes in European countries where they do not yet exist, and to review existing programmes.
Pain Med. 2018 Oct 16. doi: 10.1093/pm/pny194. [Epub ahead of print]
Recurrent vaso-occlusive pain episodes, the most common complication of sickle cell disease (SCD), cause frequent health care utilization. Studies exploring associations between patient activation and acute health care utilization for pain are lacking. We tested the hypothesis that increased activation and self-efficacy are associated with decreased health care utilization for pain in SCD.
In this cross-sectional study of adults with SCD at a tertiary medical center, we collected demographics, SCD phenotype, Patient Activation Measure levels, and self-efficacy scores using structured questionnaires. We reviewed charts to obtain disease-modifying therapy and acute health care utilization, defined as emergency room visits and hospitalizations, for vaso-occlusive pain episodes. Negative binomial regression analyses were used to test the hypothesis.
We surveyed 67 adults with SCD. The median age was 27.0 years, 53.7% were female, and 95.5% were African American. Median health care utilization for pain over one year (range) was 2.0 (0-24). Only one-third of participants (38.8%) were at the highest activation level (median [range] = 3 [1-4]). Two-thirds (65.7%) of participants had high self-efficacy (median [range] = 32.0 [13-45]). Regressions showed significant association between health care utilization and activation (incidence rate ratio [IRR] = 0.663, P = 0.045), self-efficacy (IRR = 0.947, P = 0.038), and male sex (IRR = 0.390, P = 0.003). Two outliers with high activation, self-efficacy, and health care utilization also had addictive behavior.
Many individuals with SCD have suboptimal activation and reduced self-efficacy. Higher activation and self-efficacy were associated with lower health care utilization for pain. Additional studies are needed to evaluate interventions to improve activation and self-efficacy and reduce acute health care utilization for pain.
Expert Opin Biol Ther. 2018 Oct 16:1-14. doi: 10.1080/14712598.2018.1536119. [Epub ahead of print]
Sickle cell anemia (SCA) is a hereditary blood disease caused by a single-gene mutation that affects millions of individuals world-wide. In this review, we focus on techniques to treat SCA by ex vivo genetic manipulation of hematopoietic stem/progenitor cells (HSPC), emphasizing replacement gene therapy and gene editing. Areas covered: Viral transduction of an anti-sickling β-like globin gene has been tested in pre-clinical and early-phase clinical studies, and shows promising preliminary results. Targeted editing of endogenous genes by site-directed nucleases has been developed more recently, and several approaches also are nearing clinical translation. Expert commentary: The indications and timing of gene therapy for SCA in lieu of supportive care treatment and allogeneic hematopoietic cell transplantation are still undefined. In addition, ensuring access to the treatment where the disease is endemic will present important challenges that must be addressed. Nonetheless, gene therapy and gene editing techniques have transformative potential as a universal curative option in SCA.
J Magn Reson Imaging. 2018 Oct 15. doi: 10.1002/jmri.26213. [Epub ahead of print]
Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized.
To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA.
Prospective, longitudinal study.
Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days.
3.0T T1 -weighted, T2 -weighted, and T2 -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography.
Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume.
Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman’s correlation testing.
In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004).
Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults.
Contemp Clin Trials. 2018 Oct 11;74:88-96. doi: 10.1016/j.cct.2018.10.006. [Epub ahead of print]
Many adolescents with sickle cell disease (SCD) experience recurrent and chronic pain, which has a negative impact on their health-related quality of life (HRQL). Cognitive-behavioral therapy (CBT) interventions can lead to improvement in pain and HRQL, yet due to barriers to care, most youth with SCD will not receive these interventions. To address this need for innovative programs targeting youth with SCD pain, we developed iCanCope, a tailored smartphone and web-based program that delivers a pain self-management intervention to youth with SCD. We describe the rationale, design, and implementation of a three-site parallel group randomized controlled trial with a sample of 160 adolescents with SCD and their parent caregivers. The iCanCope program includes pain self-management skills training (personalized CBT-based coping skills such as deep breathing, relaxation, and cognitive skills), goal setting, and social support. The attention control group is provided with access to a self-guided website with education about SCD. Assessments will occur at baseline (T1), immediately after completion of the intervention (12 weeks; T2) and at 6 months post-intervention (T3). Primary outcomes include coping strategies and pain intensity; secondary outcomes include physical, social, and emotional functioning, treatment satisfaction, health service use and caregiver response to youth pain behavior. Potential mediators (goal setting, self-management, and perceptions of social support) and moderators (e.g., demographic factors) will also be tested. The objective is to offer an effective, convenient, and low-cost psychosocial intervention to youth with SCD to enhance their self-management of pain.
Psychol Health Med. 2018 Oct 15:1-11. doi: 10.1080/13548506.2018.1533985. [Epub ahead of print]
The current study examines gender effects on disease knowledge and quality of life in adolescents with sickle cell disease (SCD) in Jamaica. We report the baseline results on 76 girls and 74 boys with mean age (16.9 ± 1.8 vs. 16.2 ±2.0 years), recruited in a larger intervention study. Girls had higher knowledge scores (15.3 ± 4.2 vs. 13.3 ± 4.2 p=.004), poorer overall QOL scores (70.1 ± 19.6 vs. 77.2 ± 17.8 p=0.02) but similar severity scores to boys. Girls also had significantly lower scores on many QOL domain scores: Pain occurrences over the course the past month (Pain and Hurt:77.49 ± 23.3 vs. 85.37 ± 17.13); concerns about seeking health services for pain (Worry1:63.73 ± 26.21 vs. 75.33 ± 24.62); confidence in self-management & treatment effects (Treatment: 72.25 ± 23.6 vs. 80.73 ± 18.90) and SCD disclosure & empathy from others (Communication II: 47.44 ± 1.02 vs. 61.71 ± 29.41). Knowledge was positively predicted by age, higher education, greater household possessions and was higher in girls; whereas QOL was lower in girls and those with greater disease severity and higher with higher education. In conclusion, there is a significant gender differential in disease knowledge and QOL among adolescents with SCD. Interventions will need to address the lower QOL in girls and lower disease knowledge among boys.
Thromb J. 2018 Oct 4;16:27. doi: 10.1186/s12959-018-0179-z. eCollection 2018.
Globally, sickle cell disease (SCD) is one of the most common haemoglobinopathy. Considered a public health problem, it leads to vessel occlusion, blood stasis and chronic activation of the coagulation system responsible for vaso-occlussive crises and venous thromboembolism (VTE) which may be fatal. Although contemporary observational studies suggest a relationship between SCD or sickle trait (SCT) and VTE, there is lack of a summary or meta-analysis data on this possible correlation. Hence, we propose to summarize the available evidence on the association between SCD, SCT and VTE including deep vein thrombosis (DVT) and pulmonary embolism (PE).
We searched PubMed and Scopus to identify all cross-sectional, cohort and case-control studies reporting on the association between SCD or SCT and VTE, DVT or PE in adults or children from inception to April 25, 2017. For measuring association between SCD or SCT and VTE, DVT, or PE, a meta-analysis using the random-effects method was performed to pool weighted odds ratios (OR) of risk estimates.
From 313 records initially identified from bibliographic databases, 10 studies were eligible and therefore included the meta-analysis. SCD patients had significantly higher risk for VTE (pooled OR 4.4, 95%CI 2.6-7.5, p < 0.001), DVT (OR 1.1, 95% CI 1.1-1.2, p < 0.001) and PE (pooled OR 3.7, 95% CI 3.6-3.8, p < 0.001) as compared to non SCD-adults. A higher risk of VTE (OR 33.2, 95% CI 9.7-113.4, p < 0.001) and DVT (OR 30.7, 95% CI 1.6-578.2, p = 0.02) was found in pregnant or postpartum women with SCD as compared to their counterparts without SCD. Compared to adults with SCT, the risk of VTE was higher in adults with SCD (pooled OR 3.1, 95% CI 1.8-5.3, p < 0.001), and specifically in SCD pregnant or postpartum women (OR 20.3, 95% CI 4.1-102, p = 0.0003). The risk of PE was also higher in adults with SCD (OR 3.1, 95% CCI 1.7-5.9, p = 0.0004) as compared to those with SCT. The risk of VTE was higher in individuals with SCT compared to controls (pooled OR 1.7, 95% CI 1.3-2.2, p < 0.0001), but not in pregnant or postpartum women (OR 0.9, 95% CI 0.3-2.9, p = 0.863). Compared to controls, SCT was associated with a higher risk of PE (pooled OR 2.1, 95% CI 1.2-3.8, p = 0.012) but not of DVT (pooled OR 1.2, 95% CI 0.9-1.7, p = 0.157).
Individuals with SCD, especially pregnant or postpartum women, might have a higher risk of VTE compared to the general population. SCT might also increases the risk of VTE. However, currently available data are not sufficient to allow a definite conclusion. Further larger studies are needed to provide a definitive conclusion on the association between SCD, SCT and VTE.
PMCID: PMC6171302 Free PMC Article
Conflict of interest statement
This is a systematic review and meta-analysis using published data. Therefore, an ethical approval is not required.Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Eur Respir J. 2018 Oct 10;52(4). pii: 1800272. doi: 10.1183/13993003.00272-2018. Print 2018 Oct.
Turpin M1,2,3, Chantalat-Auger C1,4,5, Parent F1,2,3,5, Driss F1,4, Lionnet F6, Habibi A7,8, Maître B9, Huertas A1,2,3, Jaïs X1,2,3, Weatherald J10,11, Montani D1,2,3, Sitbon O1,2,3, Simonneau G1,2,3, Galactéros F7,8, Humbert M1,2,3, Bartolucci P7,8, Savale L1,2,3.
The long-term effects of chronic blood exchange transfusions (BETs) on pre-capillary pulmonary hypertension complicating sickle cell disease (SCD) are unknown.13 homozygous SS SCD patients suffering from pre-capillary pulmonary hypertension and treated by chronic BETs were evaluated retrospectively. Assessments included haemodynamics, New York Heart Association Functional Class (NYHA FC), 6-min walk distance (6MWD) and blood tests.Before initiating BETs, all patients were NYHA FC III or IV, median (range) 6MWD was 223 (0-501) m and median (range) pulmonary vascular resistance (PVR) was 3.7 (2-12.5) Wood Units. After a median number of 4 BET sessions, all patients had improved to NYHA FC II or III. Significant improvements in haemodynamics were observed, including a decrease in PVR (p=0.01). There was a trend to higher 6MWD (p=0.09). Median (range) follow-up time after initiation of BETs was 25 (6-53) months. During this period, two patients decided to stop BETs. One of them died from acute right heart failure and the other experienced worsening pulmonary hypertension. Two other patients died during follow-up at 25 and 54 months after BET initiation.Chronic BETs may be a potential therapeutic option in pre-capillary pulmonary hypertension complicating SCD, leading to significant clinical and haemodynamic improvements. These data must be confirmed in a prospective study.
Am J Hematol. 2018 Oct 8. doi: 10.1002/ajh.25308. [Epub ahead of print]
The cell adhesion molecule P-selectin plays a key role in the pathogenesis of a vaso-occlusive crisis (VOC) in patients with sickle cell disease (SCD). In the double-blind, placebo-controlled phase 2 SUSTAIN study, crizanlizumab (humanized, anti-P-selectin monoclonal antibody) 5 mg/kg significantly lowered the rate of VOC in patients with SCD by 45% vs placebo. In SUSTAIN, patients with SCD were randomized to crizanlizumab 2.5 mg/kg, crizanlizumab 5 mg/kg, or placebo intravenously 14 times over 52 weeks. The primary endpoint was the annual rate of VOC with crizanlizumab vs placebo. This post-hoc descriptive analysis evaluated the proportion of patients who did not experience a VOC during the study in the following subgroups: VOCs in the year prior to study entry (2-4/5-10), SCD genotype (HbSS/non-HbSS), and concomitant hydroxyurea use (yes/no). More patients were VOC event-free in the crizanlizumab 5 mg/kg arm than in the placebo arm, including those with more frequent prior VOCs (ie, 5-10; 28.0% vs 4.2%), the HbSS genotype (31.9% vs 17.0%) and/or using concomitant hydroxyurea (33.3% vs 17.5%). Further analyses of secondary endpoints demonstrated that crizanlizumab treatment significantly increased time-to-first VOC vs placebo in these subgroups. The rates of treatment-emergent adverse events were similar between treatment arms across all subgroups. This post-hoc analysis of SUSTAIN shows that in patients with a high number of prior VOCs, on concomitant hydroxyurea and/or with the HbSS genotype, crizanlizumab treatment increases the likelihood of patients being VOC event-free and delays time-to-first VOC. This article is protected by copyright. All rights reserved.
Sickle Cell Conferences and Events
4th Annual Sickle Cell Disease Symposium for Carolinas Healthcare System
The 4th Annual Sickle Cell Disease Symposium for Carolinas Healthcare System – Atrium Health will be held on Saturday, October 27, 2018 at the Speedway Club in Charlotte, NC. The theme this year is: “4th Annual SCD Symposium: Racing to Improve the Access to Care & Outcomes for SCD.”
2018 (Re) imagining Health: Sickle Cell Anemia & Thalassaemia: An International Biomedical-Sociocultural Conference
November 16 – 17, 2018
Edmonton Clinic Health Academy, University of Alberta Edmonton, Alberta, Canada
This event will join our community of physicians, surgeons, researchers, medical practitioners and patients with a deep understanding and commitment to finding the cure for Sickle Cell Anemia.
We aim to bring together multiple voices to support and build inclusive and equitable teaching and learning environments, while increasing knowledge of the continued effects of the Sickle Cell Anemia trait. The Sickle Cell Foundation of Alberta is proud to announce the following expert speakers
Dr. Lakiea Bailey, of Georgia, USA
Dr. Carl James, of Toronto, ON
Dr. Emily Meier of Indiana, USA
Dr. Greg Guilcher of Calgary, AB
Dr. Santosh Saraf of Illinois, USA
Dr. Courtney Fitzhugh of Maryland, USA
REGISTRATION – Conference registration is now open. A variety of registration categories are available for the conference. Please see the fee details below or register online here. https://ourscfa.org/conference/
More information can be found on the conference website
www.ourscfa.org/conference Contact us at SCFA@buksa.com