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Could gene therapy cure sickle cell anemia?

An NIH clinical trial is ushering in a genetic revolution as an innovative type of gene therapy is used to attempt to cure sickle cell anemia. Dr. Jon LaPook reports. 60 Minutes Report and video https://www.cbsnews.com/news/could-gene-therapy-cure-sickle-cell-anemia-60-minutes-2020-07-26/

Effect of Inhaled Cannabis for Pain in Adults With Sickle Cell DiseaseA Randomized Clinical Trial https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2768349

Donald I. Abrams, MD1; Paul Couey, BA1; Niharika Dixit, MD1; et al

Importance  Sickle cell disease (SCD) is characterized by chronic pain and episodic acute pain caused by vasoocclusive crises, often requiring high doses of opioids for prolonged periods. In humanized mouse models of SCD, a synthetic cannabinoid has been found to attenuate both chronic and acute hyperalgesia. The effect of cannabis on chronic pain in adults with SCD is unknown.

Objective  To determine whether inhaled cannabis is more effective than inhaled placebo in relieving chronic pain in adults with SCD.

Design, Setting, and Participants  This pilot randomized clinical trial included participants with SCD with chronic pain admitted to a single inpatient clinical research center for 2 separate 5-day stays from August 2014 to April 2017. Participants inhaled either vaporized cannabis (4.4% Δ-9-tetrahydrocannabinol to 4.9% cannabidiol) 3 times daily or vaporized placebo cannabis. Pain and pain interference ratings using the Brief Pain Inventory were assessed throughout each 5-day period. Participants with SCD and chronic pain on stable analgesics were eligible to enroll. A total of 90 participants were assessed for eligibility; 56 participants were deemed ineligible, and 34 participants were enrolled. Of these, 7 participants dropped out before randomization. Of 27 randomized participants, 23 completed both treatment arms of the crossover study and were included in the final per protocol analysis. Data analysis was completed in June 2019, with the sensitivity analysis conducted in April 2020.

Interventions  Inhalation of vaporized cannabis plant (4.4% Δ-9-tetrahydrocannbinol to 4.9% cannabidiol) or placebo cannabis plant using a vaporizer 3 times daily for 5 days.

Main Outcomes and Measures  Daily pain assessed with visual analog scale and Brief Pain Inventory.

Results  A total of 23 participants (mean [SD] age, 37.6 [11.4] years; 13 [56%] women) completed the trial. The mean (SD) difference in pain rating assessment between the cannabis and placebo groups was −5.3 (8.1) for day 1, −10.9 (7.0) for day 2, −16.5 (9.2) for day 3, −8.9 (6.7) for day 4, and −8.2 (8.1) for day 5; however, none of these differences were statistically significant. There was no statistically significant mean (SD) difference in pain interference ratings between cannabis and placebo between days 1 and 5 for interference in general activities (day 1: 0.27 [0.35]; day 5: −1.0 [0.5]), walking (day 1: 0.14 [0.73]; day 5: −0.87 [0.63]), sleep (day 1: 0.59 [0.74]; day 5: −1.3 [0.8]), or enjoyment (day 1: 0.23 [0.69]; day 5: −0.91 [0.48]), but there was a statistically significant mean (SD) difference in decrease in interference with mood (day 1: 0.96 [0.59]; day 5: −1.4 [0.6]; P = .02). No differences in treatment-related adverse effects were observed. Use of concomitant opioids was similar during both treatment periods.

Conclusions and Relevance  This randomized clinical trial found that, compared with vaporized placebo, vaporized cannabis did not statistically significantly reduce pain and associated symptoms, except interference in mood, in patients with SCD with chronic pain.

ASH Releases New Clinical Practice Guidelines on Management of Pain in Sickle Cell Disease   On June 19, 2020, the American Society of Hematology (ASH) published Guidelines for Sickle Cell Disease (SCD): Management of Acute and Chronic Pain in Blood Advances. These evidence-based guidelines help support patients and health care professionals in pain management decisions for children and adults with SCD.  ASH is planning to release five SCD guideline chapters in total.  In addition to the pain at https://ashpublications.org/bloodadvances/article/4/12/2656/460974/American-Society-of-Hematology-2020-guidelines-for Blood Adv (2020) 4 (12): 2656–2701. guidelines, the following chapters are also available.   Cardiopulmonary and Kidney Disease Transfusion Support Cerebrovascular Disease The last chapter on transplantation will be published later in 2020.  Learn more about these guidelines, the development process, and find additional resources by visiting ASH’s website.
Recording Available of Webinar on Addressing the Global Burden of SCD During Pandemic and Beyond    On June 29, 2020, the United States Department of Health and Human Services, in partnership with the American Society of Hematology and SickleinAfrica, and with the participation of the World Health Organization, hosted a webinar on “Addressing the Global Burden of Sickle Cell Disease During the COVID-19 Pandemic and Beyond.”  In February 2020, global stakeholders came together at the World Bank Headquarters in Washington, DC to initiate the Global Coalition on SCD which aims to develop, organize, and implement a global multi-sectoral approach to combatting SCD.  The webinar highlighted current knowledge on the impact of COVID-19 on health care systems and access to care for individuals living with SCD. The webinar also included a discussion on the next steps of the Coalition.   The recording for the webinar can be found here.
ASH and PerkinElmer Announce Global Collaboration to Help Combat SCD  PerkinElmer, Inc., a global leader committed to innovation for a healthier world, announced a collaboration with the American Society of Hematology (ASH) to support a new effort to increase capacity for newborn screening, education, and clinical interventions for SCD in sub-Saharan Africa.  Through this collaboration, PerkinElmer and ASH will also enhance advocacy through the Consortium on Newborn Screening in Africa (CONSA), a collaboration with African hematologists, public health authorities, and ASH dedicated to studying the benefits of newborn screening and early therapeutic interventions for SCD. CONSA introduces standard-of-care practices for screening and early intervention therapies (such as antibiotic prophylaxis and immunizations) with plans to screen 10,000-20,000 newborns per year in each sub-Saharan country and provide clinical follow-up for babies who screen positive for SCD. Stay Connected with the ASH Research Collaborative     The ASH Research Collaborative (ASH RC) recently launched a revamped website and also new ASH RC Newsletter.  Stay abreast of the two core elements of the ASH RC –its Data Hub and Sickle Cell Disease Clinical Trials Network – by visiting the website and signing-up for their newsletter.   Visit New Website to Learn about Gene Therapy    Bluebird bio recently launched a new website called genehome as a source to learn about gene therapy.  As the field of gene therapy continues to evolve, genehome is a go-to source for comprehensive, understandable, and unbiased education. Gene therapy has the potential to treat many diseases, but the science behind it is not always easy to understand.    SCD and COVID-19   CDC Adds SCD to List of People of Severe Risk of COVID-19   In late June, the Centers for Disease Control and Prevention added sickle cell disease (SCD) to the list of conditions that are at increased risk of severe illness from COVID-19.  View their webpage about extra precautions individuals with SCD can take during COVID-19.     SECURE-SCD Registry Group Article on Early Findings of COVID-19 in Individuals with SCD.   An early release version of the article entitled Coronavirus Disease among Persons with Sickle Cell Disease (SCD), United States, March 20–May 21, 2020 was recently published in the Centers for Disease Control and Prevention’s Emerging Infectious Disease Journal .  The article, authored by the SECURE-SCD Registry Group from the Medical College of Wisconsin, reports that among 178 persons with SCD in the United States who were reported to an SCD–coronavirus disease case registry, 122 (69%) were hospitalized and 13 (7%) died.  Learn more about the Secure-SCD Registry here.   SCD and COVID-19 Resources   The following links are frequently updated with timely information for the community and providers. American Society of Hematology COVID-19 Resources Checklist for SCD Patients Presenting to the Emergency Department (ED) During Pandemic – Assists in the evaluation of individuals with SCD in ED presenting with symptoms concerning for COVID-19 and/or complications of SCD, with SCD-specific considerations for evaluation and treatment. Frequently Asked Clinical Questions on COVID-19 and SCD SCDAA’s Advisory and Resources on SCD and COVID-19 for Community and Providers Health Alert for People with Sickle Cell Disease and their Caregivers Provider Advisory:  An Outline to Decrease Burden and Minimize Morbidity – Guidance for the acute and chronic disease management of individuals with SCD. Sub-Saharan African Provider Advisory – Adapted from the general Provider Advisor Sickle Cell Community Consortium Offers Resources to Address Challenges of Pandemic – Resources for the community focused on social services, mental health support, and education support. Be The Match Offers Counseling for Sickle Cell Warriors During Pandemic – Free counseling services to sickle cell warriors and their loved ones. 

Articles in the medical literature

  1. Blood transfusion for preventing primary and secondary stroke in people with sickle cell disease Cochrane Database Syst Rev. 2020 Jul 27;7:CD003146. doi: 10.1002/14651858.CD003146.pub4. Authors Lise J Estcourt  1 Ruchika Kohli  2 Sally Hopewell  3 Marialena Trivella  4 Winfred C Wang  5 Abstract Background: Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation. This is an update of a Cochrane Review first published in 2002, and last updated in 2017. Objectives: To assess risks and benefits of chronic blood transfusion regimens in people with sickle cell disease for primary and secondary stroke prevention (excluding silent cerebral infarcts). Search methods: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 8 October 2019. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register: 19 September 2019. Selection criteria: Randomised controlled trials comparing red blood cell transfusions as prophylaxis for stroke in people with sickle cell disease to alternative or standard treatment. There were no restrictions by outcomes examined, language or publication status. Data collection and analysis: Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results: We included five trials (660 participants) published between 1998 and 2016. Four of these trials were terminated early. The vast majority of participants had the haemoglobin (Hb)SS form of sickle cell disease. Three trials compared regular red cell transfusions to standard care in primary prevention of stroke: two in children with no previous long-term transfusions; and one in children and adolescents on long-term transfusion. Two trials compared the drug hydroxyurea (hydroxycarbamide) and phlebotomy to long-term transfusions and iron chelation therapy: one in primary prevention (children); and one in secondary prevention (children and adolescents). The quality of the evidence was very low to moderate across different outcomes according to GRADE methodology. This was due to the trials being at a high risk of bias due to lack of blinding, indirectness and imprecise outcome estimates. Red cell transfusions versus standard care Children with no previous long-term transfusions Long-term transfusions probably reduce the incidence of clinical stroke in children with a higher risk of stroke (abnormal transcranial doppler velocities or previous history of silent cerebral infarct), risk ratio 0.12 (95% confidence interval 0.03 to 0.49) (two trials, 326 participants), moderate quality evidence. Long-term transfusions may: reduce the incidence of other sickle cell disease-related complications (acute chest syndrome, risk ratio 0.24 (95% confidence interval 0.12 to 0.48)) (two trials, 326 participants); increase quality of life (difference estimate -0.54, 95% confidence interval -0.92 to -0.17) (one trial, 166 participants); but make little or no difference to IQ scores (least square mean: 1.7, standard error 95% confidence interval -1.1 to 4.4) (one trial, 166 participants), low quality evidence. We are very uncertain whether long-term transfusions: reduce the risk of transient ischaemic attacks, Peto odds ratio 0.13 (95% confidence interval 0.01 to 2.11) (two trials, 323 participants); have any effect on all-cause mortality, no deaths reported (two trials, 326 participants); or increase the risk of alloimmunisation, risk ratio 3.16 (95% confidence interval 0.18 to 57.17) (one trial, 121 participants), very low quality evidence. Children and adolescents with previous long-term transfusions (one trial, 79 participants) We are very uncertain whether continuing long-term transfusions reduces the incidence of: stroke, risk ratio 0.22 (95% confidence interval 0.01 to 4.35); or all-cause mortality, Peto odds ratio 8.00 (95% confidence interval 0.16 to 404.12), very low quality evidence. Several review outcomes were only reported in one trial arm (sickle cell disease-related complications, alloimmunisation, transient ischaemic attacks). The trial did not report neurological impairment, or quality of life. Hydroxyurea and phlebotomy versus red cell transfusions and chelation Neither trial reported on neurological impairment, alloimmunisation, or quality of life. Primary prevention, children (one trial, 121 participants) Switching to hydroxyurea and phlebotomy may have little or no effect on liver iron concentrations, mean difference -1.80 mg Fe/g dry-weight liver (95% confidence interval -5.16 to 1.56), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy has any effect on: risk of stroke (no strokes); all-cause mortality (no deaths); transient ischaemic attacks, risk ratio 1.02 (95% confidence interval 0.21 to 4.84); or other sickle cell disease-related complications (acute chest syndrome, risk ratio 2.03 (95% confidence interval 0.39 to 10.69)), very low quality evidence. Secondary prevention, children and adolescents (one trial, 133 participants) Switching to hydroxyurea and phlebotomy may: increase the risk of sickle cell disease-related serious adverse events, risk ratio 3.10 (95% confidence interval 1.42 to 6.75); but have little or no effect on median liver iron concentrations (hydroxyurea, 17.3 mg Fe/g dry-weight liver (interquartile range 10.0 to 30.6)); transfusion 17.3 mg Fe/g dry-weight liver (interquartile range 8.8 to 30.7), low quality evidence. We are very uncertain whether switching to hydroxyurea and phlebotomy: increases the risk of stroke, risk ratio 14.78 (95% confidence interval 0.86 to 253.66); or has any effect on all-cause mortality, Peto odds ratio 0.98 (95% confidence interval 0.06 to 15.92); or transient ischaemic attacks, risk ratio 0.66 (95% confidence interval 0.25 to 1.74), very low quality evidence. Authors’ conclusions: There is no evidence for managing adults, or children who do not have HbSS sickle cell disease. In children who are at higher risk of stroke and have not had previous long-term transfusions, there is moderate quality evidence that long-term red cell transfusions reduce the risk of stroke, and low quality evidence they also reduce the risk of other sickle cell disease-related complications. In primary and secondary prevention of stroke there is low quality evidence that switching to hydroxyurea with phlebotomy has little or no effect on the liver iron concentration. In secondary prevention of stroke there is low-quality evidence that switching to hydroxyurea with phlebotomy increases the risk of sickle cell disease-related events. All other evidence in this review is of very low quality. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Publication types Review Full-text links 3. Neuropathic Pain and Sickle Cell Disease: a Review of Pharmacologic Management Curr Pain Headache Rep. 2020 Jul 24;24(9):52. doi: 10.1007/s11916-020-00885-5. Authors Mariam Salisu Orhurhu  1 Robert Chu  2 Lauren Claus  2 Jacob Roberts  2 Bisi Salisu  3 Ivan Urits  4 Ejovwoke Orhurhu  5 Omar Viswanath  6   7   8   9 Alan D Kaye  6   7   8   9 Aaron J Kaye  10 Vwaire Orhurhu  11 Abstract Purpose of review: Sickle cell disease (SCD) remains among the most common and severe monogenic disorders present in the world today. Although sickle cell pain has been traditionally characterized as nociceptive, a significant portion of sickle cell patients has reported neuropathic pain symptoms. Our review article will discuss clinical aspects of SCD-related neuropathic pain, epidemiology of neuropathic pain among individuals with SCD, pain mechanisms, and current and future potential pharmacological interventions. Recent findings: Neuropathic pain in SCD is a complicated condition that often has a lifelong and significant negative impact on life; therefore, improved pain management is considered a significant and unmet need. Neuropathic pain mechanisms are heterogeneous, and the difficulty in determining their individual contribution to specific pain types may contribute to poor treatment outcomes in this population. Our review article outlines several pharmacological modalities which may be employed to treat neuropathic pain in SCD patients. Keywords: Chronic pain; Neuropathic pain; Pharmacologic management; Sickle cell disease. Publication types Review Full-text links 4. Splenic Sequestration Crisis Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jul 6. Authors Ian Kane  1 Shivaraj Nagalli  2 Free Books & Documents Excerpt Splenic sequestration is a feared complication of sickle cell anemia that primarily affects young children. It is an acute drop in hemoglobin of 2 g/dL accompanied by splenomegaly. The spleen is at particular risk for complications from sickle cell anemia due to its role as a filter of the blood. The spleen is composed of three areas; white pulp, red pulp, and a transitional zone, and each plays a role within the immune system. A minority of blood flow entering the spleen (approximately 10%) is directed outside of the vessels into the parenchyma of the red pulp, where the red blood cells (RBCs) become exposed to reticuloendothelial cells such as macrophages which clear away abnormal cells or other pathogens. To re-enter the vascular system, the RBCs must squeeze through narrow slits in the endothelium of the venous sinuses. The organization of the white pulp of the spleen is predominantly T-cell periarteriolar sheaths and follicles, consisting of B cells. These B cells are critical in the production of IgM antibodies capable of opsonizing encapsulated bacteria such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenza type B. Among children with sickle cell anemia, the spleen gradually loses function and size over the first five years of life due to repeated episodes of autoinfarction and scarring. Children with less severe variants of sickle cell disease such as hemoglobin SC disease or sickle cell-beta thalassemia may have preserved some splenic function into adulthood, and studies have shown that treatment with hydroxyurea can preserve and even result in some recovery of splenic function. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 5. Hematopoietic stem cell transplantation for people with sickle cell disease Cochrane Database Syst Rev. 2020 Jul 3;7:CD007001. doi: 10.1002/14651858.CD007001.pub5. Authors Chioma Oringanje  1 Eneida Nemecek  2 Oluseyi Oniyangi  3 Abstract Background: Sickle cell disease is a genetic disorder involving a defect in the red blood cells due to its sickled hemoglobin. The main therapeutic interventions include preventive and supportive measures. Hematopoietic stem cell transplantations are carried out with the aim of replacing the defective cells and their progenitors (hematopoietic (i.e. blood forming) stem cells) in order to correct the disorder. This is an update of a previously published review. Objectives: To determine whether stem cell transplantation can improve survival and prevent symptoms and complications associated with sickle cell disease. To examine the risks of stem cell transplantation against the potential long-term gain for people with sickle cell disease. Search methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Group’s Haemoglobinopathies Trials Register complied from electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (updated each new issue of the Cochrane Library) and quarterly searches of MEDLINE. We also searched trial registries for ongoing trials up to April 2020. Date of the most recent search of the Group’s Haemoglobinopathies Trials Register: 09 December 2019. Selection criteria: Randomized controlled and quasi-randomized trials that compared any method of stem cell transplantation with either each other or with any of the preventive or supportive interventions (e.g. periodic blood transfusion, use of hydroxyurea, antibiotics, pain relievers, supplemental oxygen) in people with sickle cell disease irrespective of the type of sickle cell disease, gender and setting. Data collection and analysis: No trials were eligible for inclusion in the review. Main results: We identified 12 potentially-eligible trials by the searches; we excluded 11 of these and the remaining trial is an ongoing trial that may be eligible for inclusion in a future version of the review. Authors’ conclusions: Reports on the use of hematopoietic stem cell transplantation improving survival and preventing symptoms and complications associated with sickle cell disease are currently limited to observational and other less robust studies. We did not find any eligible randomized controlled trials assessing the benefit or risk of hematopoietic stem cell transplantations. However, there is an ongoing quasi-randomized trial comparing hematopoietic stem cell transplantation with standard care, Thus, this systematic review identifies the need for a multicentre randomized controlled trial assessing the benefits and possible risks of hematopoietic stem cell transplantations comparing sickle status and severity of disease in people with sickle cell disease. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Publication types Review Full-text links 6. Preoperative blood transfusions for sickle cell disease Cochrane Database Syst Rev. 2020 Jul 2;7:CD003149. doi: 10.1002/14651858.CD003149.pub4. Authors Lise J Estcourt  1 Catherine Kimber  2 Marialena Trivella  3 Carolyn Doree  2 Sally Hopewell  4 Abstract Background: Sickle cell disease (SCD) is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. SCD can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Surgical interventions are more common in people with SCD, and occur at much younger ages than in the general population. Blood transfusions are frequently used prior to surgery and several regimens are used but there is no consensus over the best method or the necessity of transfusion in specific surgical cases. This is an update of a Cochrane Review. Objectives: To determine whether there is evidence that preoperative blood transfusion in people with SCD undergoing elective or emergency surgery reduces mortality and perioperative or sickle cell-related serious adverse events. To compare the effectiveness of different transfusion regimens (aggressive or conservative) if preoperative transfusions are indicated in people with SCD. Search methods: We searched for relevant trials in the Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 28 January 2020 We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 19 September 2019. Selection criteria: All randomised controlled trials and quasi-randomised controlled trials comparing preoperative blood transfusion regimens to different regimens or no transfusion in people with SCD undergoing elective or emergency surgery. There was no restriction by outcomes examined, language or publication status. Data collection and analysis: Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results: Three trials with 990 participants were eligible for inclusion in the review. There were no ongoing trials identified. These trials were conducted between 1988 and 2011. The majority of people included had haemoglobin (Hb) SS SCD. The majority of surgical procedures were considered low or intermediate risk for developing sickle cell-related complications. Aggressive versus simple red blood cell transfusions One trial (551 participants) compared an aggressive transfusion regimen (decreasing sickle haemoglobin to less than 30%) to a simple transfusion regimen (increasing haemoglobin to 100 g/L). This trial re-randomised participants and therefore quantitative analysis was only possible on two subsets of data: participants undergoing cholecystectomy (230 participants); and participants undergoing tonsillectomy or adenoidectomy surgeries (107 participants). Data were not combined as we do not know if any participant received both surgeries. Overall, the quality of the evidence was very low across different outcomes according to GRADE methodology. This was due to the trial being at high risk of bias primarily due to lack of blinding, indirectness and the outcome estimates being imprecise. Cholecystectomy subgroup results are reported in the abstract. Results for both subgroups were similar. There was no difference in all-cause mortality between people receiving aggressive transfusions and those receiving conservative transfusions. No deaths occurred in either subgroup. There were no differences between the aggressive transfusion group and conservative transfusion group in the number of people developing: • an acute chest syndrome, risk ratio (RR) 0.84 (95% confidence interval (CI) 0.38 to 1.84) (one trial, 230 participants, very low-quality evidence); • vaso-occlusive crisis, risk ratio 0.30 (95% CI 0.09 to 1.04) (one trial, 230 participants, very low quality evidence); • serious infection, risk ratio 1.75 (95% CI 0.59 to 5.18) (one trial, 230 participants, very low-quality evidence); • any perioperative complications, RR 0.75 (95% CI 0.36 to 1.55) (one trial, 230 participants, very low-quality evidence); • a transfusion-related complication, RR 1.85 (95% CI 0.89 to 3.88) (one trial, 230 participants, very low-quality evidence). Preoperative transfusion versus no preoperative transfusion Two trials (434 participants) compared a preoperative transfusion plus standard care to a group receiving standard care. Overall, the quality of the evidence was low to very low across different outcomes according to GRADE methodology. This was due to the trials being at high risk of bias due to lack of blinding, and outcome estimates being imprecise. One trial was stopped early because more people in the no transfusion arm developed an acute chest syndrome. There was no difference in all-cause mortality between people receiving preoperative transfusions and those receiving no preoperative transfusions (two trials, 434 participants, no deaths occurred). There was significant heterogeneity between the two trials in the number of people developing an acute chest syndrome, a meta-analysis was therefore not performed. One trial showed a reduced number of people developing acute chest syndrome between people receiving preoperative transfusions and those receiving no preoperative transfusions, risk ratio 0.11 (95% confidence interval 0.01 to 0.80) (65 participants), whereas the other trial did not, RR 4.81 (95% CI 0.23 to 99.61) (369 participants). There were no differences between the preoperative transfusion groups and the groups without preoperative transfusion in the number of people developing: • a vaso-occlusive crisis, Peto odds ratio (OR) 1.91 (95% confidence interval 0.61 to 6.04) (two trials, 434 participants, very low-quality evidence). • a serious infection, Peto OR 1.29 (95% CI 0.29 to 5.71) (two trials, 434 participants, very low-quality evidence); • any perioperative complications, RR 0.24 (95% CI 0.03 to 2.05) (one trial, 65 participants, low-quality evidence). There was an increase in the number of people developing circulatory overload in those receiving preoperative transfusions compared to those not receiving preoperative transfusions in one of the two trials, and no events were seen in the other trial (no meta-analysis performed). Authors’ conclusions: There is insufficient evidence from randomised trials to determine whether conservative preoperative blood transfusion is as effective as aggressive preoperative blood transfusion in preventing sickle-related or surgery-related complications in people with HbSS disease. There is very low quality evidence that preoperative blood transfusion may prevent development of acute chest syndrome. Due to lack of evidence this review cannot comment on management for people with HbSC or HbSβ+ disease or for those with high baseline haemoglobin concentrations. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Publication types Review Full-text links 7. Retinopathy Hemoglobinopathies Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jul 2. Authors Kaberi B. Feroze  1 Alexandre M. Azevedo  2   Free Books & Documents Excerpt Hemoglobinopathy refers to genetic disorders which are characterized by the inheritance of either an abnormal hemoglobin as in sickle cell disease or an insufficient production of hemoglobin chains as in thalassemia. James Herrick first described sickle cell disease from observing the peripheral smear of a West Indian patient. The ocular manifestations of sickle cell disease were described by Cook in 1930 when he noticed retinal hemorrhages in a patient who died of subarachnoid hemorrhage. A Detroit physician who was studying Italian children with severe anemia, poor growth, and early death first discovered thalassemia in 1925. Ocular involvement in beta thalassemia can occur because of the disease itself, because of the iron overload as a result of blood transfusions, or because of desferrioxamine used to treat the iron overload. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 9. Sickle Cell Crisis Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 28. Authors Mahesh B. Borhade  1 Noah P. Kondamudi  2 Free Books & Documents Excerpt Sickle cell disease (SCD) is a group of inherited red blood cell disorders affecting about 1 in 500 African American children and 1 in 36,000 Hispanic American children. SCD results in anemia and “sickle cell crisis” (SCC). The main clinical feature of sickle cell disease is the ”acute painful crisis,’’ which often requires hospitalization. The term “sickle cell crisis” is used to describe several acute conditions such as the vaso-occlusive crisis (acute painful crisis), aplastic crisis, splenic sequestration crisis, hyperhemolytic crisis, hepatic crisis, dactylitis, and acute chest syndrome. Other acute complications include pneumonia, meningitis, sepsis and osteomyelitis, stroke, avascular necrosis, priapism, and venous thromboembolism. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 10. Sickle cell trait and the potential risk of severe coronavirus disease 2019-A mini-review Eur J Haematol. 2020 Jun 26;10.1111/ejh.13478. doi: 10.1111/ejh.13478. Online ahead of print. Authors Tawakalitu Abosede Kehinde  1 Mayowa Azeez Osundiji  2 Free PMC article Abstract Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 among African Americans, although detailed epidemiological study data is pending. Sickle cell disease (SCD) disproportionately affects Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America), and some Mediterranean countries. The carrier frequency for SCD is high among African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine. Keywords: Thromboembolism; Vaso-Occlusive Crisis (VOC); acute chest syndrome; coronavirus disease 2019; sickle cell disease; sickle cell trait. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. 75 references Publication types Review Full-text links 11. Management of Hemoglobin Disorders During the COVID-19 Pandemic Front Med (Lausanne). 2020 Jun 9;7:306. doi: 10.3389/fmed.2020.00306. eCollection 2020. Authors Sanjana Fatema Chowdhury  1 Saeed Anwar  2 Free PMC article Abstract The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has become a global public health concern after being first reported in China and has subsequently spread worldwide. It causes mild to severe respiratory illness with some flu-like symptoms. The causal virus behind this disease, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), conceivably attacks the receptors of the respiratory system of the human body but has no strict evidence of attacking the blood cells yet. However, patients with hemoglobin disorders (e.g., sickle cell anemia, thalassemia) are vulnerable to this global health situation due to their clinical complications. Such patients are generally more prone to viral and bacterial infections, which can worsen their physical condition. Some of these patients present immunocompromised conditions, e.g., splenectomized or post-transplant patients. Therefore, they should follow some preventive steps such as shielding as well as the general guidelines for the COVID-19 pandemic. Transfusion dependent patients require regular monitoring for iron overload, and iron chelation therapy may be stopped by the physician depending on the situation. This article reviews the management strategies and provides some crucial recommendations for people in the corner with hemoglobin disorders. Keywords: COVID-19; SARS-CoV-2; clinical management; hemoglobin; hemoglobinopathies; iron chelation therapy; sickle cell diseases; thalassemia. Copyright © 2020 Chowdhury and Anwar. 40 references Publication types Review Full-text links 12. Sickle Cell Nephropathy Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 26. Authors Narothama R. Aeddula  1 Mainak Bardhan  2 Krishna M. Baradhi  3 Free Books & Documents Excerpt Sickle cell disease (SCD), first discovered in West Africa is an autosomal recessive hemoglobin disorder, predominantly affecting persons of African, Mediterranean, Indian, and Middle Eastern descent. It results from the replacement of glutamate for valine at the sixth amino acid of the beta-globin chain. The mutation results in hemoglobin S (HbS) tetramers that accumulate during tissue hypoxia, oxidative stress or dehydration. The accumulation leads to red blood cell sickling, early destruction of erythrocytes, and widespread vaso-occlusive episodes (VOC), subsequently resulting in multiorgan damage. Some of the renal complications, collectively known as sickle cell nephropathy (SCN), include hematuria, hyposthenuria, renal papillary necrosis, proteinuria, renal tubular disorders, acute and chronic kidney injury, sickle cell glomerulopathy, and renal medullary carcinoma. Clinically significant renal involvement occurs more frequently in sickle cell disease than in sickle cell trait or in combined hemoglobinopathies, except renal medullary carcinoma, which appears to be more common among sickle cell trait patients. Natural history of SCD is highly variable with reduced life expectancy with multiorgan damage in symptomatic patients. In general, all patients have a reduced lifespan. Median survival in the United States and Jamaica is 45 to 55 years. Natural history by age in SCD is as follows: The primary cause of death in younger patients is usually infection; whereas, in older patients, the primary cause of death is mostly irreversible organ damage. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 13. Acute Chest Syndrome Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 24. Authors Amanda Friend  1 Daniel Girzadas  1 Free Books & Documents Excerpt Acute chest syndrome (ACS) is the result of various inciting events causing vaso-occlusion within the pulmonary vasculature of patients with sickle cell disease (SCD). ACS can occur in any SCD phenotype. However, it is most common in HbSS. ACS can progress quickly and is the most common cause of death in patients with SCD. Therefore, it is important to make the diagnosis and begin treatment as soon as possible. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 14. Abdominal Manifestations of Sickle Cell Disease Curr Probl Diagn Radiol. 2020 Jun 1;S0363-0188(20)30113-4. doi: 10.1067/j.cpradiol.2020.05.012. Online ahead of print. Authors Nikhar P Kinger  1 Courtney C Moreno  2 Frank H Miller  3 Pardeep K Mittal  4 Abstract Sickle cell disease is a debilitating hematologic process that affects the entire body. Disease manifestations in the abdomen most commonly result from vaso-occlusion, hemolysis, or infection due to functional asplenia. Organ specific manifestations include those involving the liver (eg, hepatopathy, iron deposition), gallbladder (eg, stone formation), spleen (eg, infarction, abscess formation, sequestration), kidneys (eg, papillary necrosis, infarction), pancreas (eg, pancreatitis), gastrointestinal tract (eg, infarction), reproductive organs (eg, priapism, testicular atrophy), bone (eg, marrow changes, avascular necrosis), vasculature (eg, vasculopathy), and lung bases (eg, acute chest syndrome, infarction). Imaging provides an important clinical tool for evaluation of acute and chronic disease manifestations and complications. In summary, there are multifold abdominal manifestations of sickle cell disease. Recognition of these sequela helps guide management and improves outcomes. The purpose of this article is to review abdominal manifestations of sickle cell disease and discuss common and rare complications of the disease within the abdomen. 15. Risk factors for hemolytic transfusion reactions resulting from ABO and minor red cell antigen incompatibility: From mislabeled samples to stem cell transplant and sickle cell disease Blood Rev. 2020 Jun 6;100719. doi: 10.1016/j.blre.2020.100719. Online ahead of print. Authors Eric A Gehrie  1 Bipin N Savani  2 Garrett S Booth  3 Abstract Advances in laboratory testing, pathogen reduction and donor qualification have dramatically reduced the risk of acquiring an infection from a blood transfusion. Despite this progress, the most feared complication of transfusion – a hemolytic reaction due to incompatibility between donor and recipient – remains, with essentially no recent progress in the prevention or recognition of this rare but frequently lethal complication. Herein, the role that compatibility testing and transfusion practice play in the occurrence of acute hemolysis are described, with a special emphasis on clinical scenarios confer an increased risk of a severe hemolytic reaction in response to red blood cell or platelet transfusion. In addition, the signs and symptoms of a severe hemolytic reaction are summarized, along with the initial approach to clinical management. Full-text links 16. Integrative approaches to treating pain in sickle cell disease: Pre-clinical and clinical evidence Complement Ther Med. 2020 Jun;51:102394. doi: 10.1016/j.ctim.2020.102394. Epub 2020 May 11. Authors Varun Sagi  1 Donovan A Argueta  2 Stacy Kiven  2 Kalpna Gupta  3 Free PMC article Abstract Sickle cell disease (SCD) is a genetic disorder characterized by hemolysis, end-organ damage, inflammation, and pain. Recurrent and unpredictable episodes of acute pain due to vaso-occlusive crises are a unique feature of SCD. Many patients also develop lifelong chronic pain. Opioids are the primary method of pain treatment in SCD; however, continued use is associated with several adverse effects. Integrative approaches to treating pain in SCD are increasingly being explored to prevent the side effects associated with opioids. In this review, we highlight the mechanisms of pain in SCD and describe mechanism-based integrative approaches for treating pain. Keywords: Pain; Sickle cell disease. Copyright © 2020 Elsevier Ltd. All rights reserved. Conflict of interest statement Declaration of Competing Interest Kalpna Gupta: Fera Pharmaceuticals LLC: Consultancy, Honoraria; Tautona Group: Consultancy, Honoraria; Novartis advisory group: Honoraria; CSL Behring, honoraria; Grifols, Research Grant; 1910 Genetics, Resaerch Grant. All other authors declare no conflict of interest. Publication types Review Grant support R01 HL147562/HL/NHLBI NIH HHS/United States U01 HL117664/HL/NHLBI NIH HHS/United States Full-text links 17. Sickle Cell Anemia Review In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan. 2020 Jun 7. Authors Ankit Mangla  1 Moavia Ehsan  2 Smita Maruvada Free Books & Documents Excerpt Sickle cell anemia is the most severe form of sickle cell disease and is the homozygous state for hemoglobin S. Sickle cell anemia is prevalent in Africa, the Middle East, and parts of India. It is common in geographical areas where malaria is widespread. Hemoglobin in most individuals is present in soluble form. However, in sickle cell disease, hemoglobin precipitates as insoluble crystals which lead to an abnormal shape and size of RBCs with subsequent phagocytosis of the effected corpuscles.,, The disorder typically affects Africans and people of Mediterranean ancestry. Carriers of the sickle cell trait do not suffer from the disease. Copyright © 2020, StatPearls Publishing LLC. Publication types Review Full-text links StatPearls [Internet] 18. Vitamin D supplementation for sickle cell disease Cochrane Database Syst Rev. 2020 May 28;5:CD010858. doi: 10.1002/14651858.CD010858.pub3. Authors Htoo Htoo Kyaw Soe  1 Adinegara Bl Abas  2 Nan Nitra Than  3 Han Ni  4 Jaspal Singh  5 Abdul Razzak Bin Mohd Said  6 Ifeyinwa Osunkwo  7 Abstract Background: Sickle cell disease (SCD) is a genetic chronic haemolytic and pro-inflammatory disorder. With increased catabolism and deficits in energy and nutrient intake, individuals with SCD suffer multiple macro- and micro-nutritional deficiencies, including vitamin D deficiency. This is an update of a previous review. Objectives: To investigate the effects of vitamin D supplementation in children and adults with SCD and to compare different dose regimens. To determine the effects of vitamin D supplementation on general health (e.g. growth status and health-related quality of life), on musculoskeletal health (including bone mineral density, pain crises, bone fracture and muscle health), on respiratory health (including lung function, acute chest syndrome, acute exacerbation of asthma and respiratory infections) and the safety of vitamin D supplementation. Search methods: We searched the Cochrane Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 19 March 2020. We also searched database such as PubMed, clinical trial registries and the reference lists of relevant articles and reviews. Date of last search: 14 January 2020. Selection criteria: Randomised controlled trials (RCTs) and quasi-RCTs comparing oral administration of any form of vitamin D supplementation at any dose and for any duration to another type or dose of vitamin D or placebo or no supplementation in people with SCD, of all ages, gender, and phenotypes. Data collection and analysis: Two authors independently extracted the data and assessed the risk of bias of the included studies. They used the GRADE guidelines to assess the quality of the evidence. Main results: Vitamin D versus placebo One double-blind RCT (n = 39) compared oral vitamin D3 (cholecalciferol) supplementation (20 participants) to placebo (19 participants) for six weeks. Only 25 participants completed the full six months of follow-up. The study had a high risk of bias due to incomplete outcome data, but a low risk of bias for randomisation, allocation concealment, blinding (of participants, personnel and outcome assessors) and selective outcome reporting; and an unclear risk of other biases. Vitamin D supplementation probably led to higher serum 25(OH)D levels at eight weeks, mean difference (MD) 29.79 (95% confidence interval (CI) 26.63 to 32.95); at 16 weeks, MD 12.67 (95% CI 10.43 to 14.90); and at 24 weeks, MD 15.52 (95% CI 13.50 to 17.54) (moderate-quality evidence). There was little or no difference in adverse events (tingling of lips or hands) between the vitamin D and placebo groups, risk ratio 3.16 (95% CI 0.14 to 72.84) (low-quality evidence). Vitamin D supplementation probably caused fewer pain days compared to the placebo group at eight weeks, MD -10.00 (95% CI -16.47 to -3.53) (low-quality evidence), but probably led to a lower (worse) health-related quality of life score (change from baseline in physical functioning PedsQL scores); at both 16 weeks, MD -12.56 (95% CI -16.44 to -8.69) and 24 weeks, MD -12.59 (95% CI -17.43 to -7.76), although this may not be the case at eight weeks (low-quality evidence). Vitamin D supplementation regimens compared Two double-blind RCTs (83 participants) compared different regimens of vitamin D. One RCT (n = 62) compared oral vitamin D3 7000 IU/day to 4000 IU/day for 12 weeks, while the second RCT (n = 21) compared oral vitamin D3 100,000 IU/month to 12,000 IU/month for 24 months. Both RCTs had low risk of bias for blinding (of participants, personnel and outcome assessors) and incomplete outcome data, but the risk of selective outcome reporting bias was high. The bias from randomisation and allocation concealment was low in one study but not in the second. There was an unclear risk of other biases. When comparing oral vitamin D 100,000 IU/month to 12,000 IU/month, the higher dose may have resulted in higher serum 25(OH)D levels at one year, MD 16.40 (95% CI 12.59 to 20.21) and at two years, MD 18.96 (95% CI 15.20 to 22.72) (low-quality evidence). There was little or no difference in adverse events between doses (low-quality evidence). There were more episodes of acute chest syndrome in the high-dose group, at one year, MD 0.27 (95% CI 0.02 to 0.52) but there was little or no difference at two years, MD 0.09 (95% CI -0.04 to 0.22) (moderate-quality evidence). At one year and two years there was also little or no difference between the doses in the presence of pain (moderate-quality evidence) or forced expiratory volume in one second % predicted. However, the high-dose group had lower values for % predicted forced vital capacity at both one and two years, MD -7.20% predicted (95% CI -14.15 to -0.25) and MD -7.10% predicted (95% CI -14.03 to -0.17), respectively. There were little or no differences between dose regimens in the muscle health of either hand or the dominant hand. The study comparing oral vitamin D3 7000 IU/day to 4000 IU/day (21 participants) did not provide data for analysis, but median serum 25(OH)D levels were reported to be lower in the low-dose group at both six and 12 weeks. At 12 weeks the median serum parathyroid hormone level was lower in the high-dose group. Authors’ conclusions: We included three RCTs of varying quality. We consider that the current evidence presented in this review is not of sufficient quality to guide clinical practice. Until further evidence becomes available, clinicians should consider the relevant existing guidelines for vitamin D supplementation and dietary reference intakes for calcium and vitamin D. Well-designed RCTs of parallel design, are required to determine the effects and the safety of vitamin D supplementation as well as to assess the relative benefits of different doses in children and adults with SCD. Trial registration: ClinicalTrials.gov NCT03417947. Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Update of Vitamin D supplementation for sickle cell disease. Soe HH, Abas AB, Than NN, Ni H, Singh J, Said AR, Osunkwo I. Cochrane Database Syst Rev. 2017 Jan 20;1(1):CD010858. doi: 10.1002/14651858.CD010858.pub2. PMID: 28105733Free PMC article.Updated.Review. Publication types Review Research Support, Non-U.S. Gov’t Associated data ClinicalTrials.gov/NCT03417947 Full-text links 19. Managing sickle cell patients with COVID-19 infection: the need to pool our collective experience Br J Haematol. 2020 Jul;190(2):e86-e89. doi: 10.1111/bjh.16880. Epub 2020 Jun 11. Authors Kamal Kant Sahu  1 Ahmad Daniyal Siddiqui  1 Jan Cerny  2 Free PMC article Abstract Coronavirus disease 19 (COVID‐19) has posed unparalleled challenges for health care communities, the general population, and in particular, for patients suffering from various comorbidities. Patients with hematological disorders, both benign and malignant need special attention during this crisis time to ensure uninterrupted delivery of optimal care (Sahu & Siddiqui, 2020). Full-text links 20. Current Issues and Options for Hormonal Contraception in Adolescents and Young Adult Women With Sickle Cell Disease: An Update for Health Care Professionals Mediterr J Hematol Infect Dis. 2020 May 1;12(1):e2020032. doi: 10.4084/MJHID.2020.032. eCollection 2020. Authors Vincenzo De Sanctis  1 Ashraf T Soliman  2 Shahina Daar  3 Duran Canatan  4 Salvatore Di Maio  5 Christos Kattamis  6 Affiliations 1 Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy. 2 Department of Pediatrics, University of Alexandria, Alexandria, Egypt. 3 Department of Haematology, College of Medicine and Health Sciences, Sultan Qaboos University, Sultanate of Oman. 4 Antalya Genetic Diseases Center, Antalya, Turkey. 5 Emeritus Director in Pediatrics, Children’s Hospital “Santobono-Pausilipon,” Naples, Italy. 6 First Department of Paediatrics, National Kapodistrian University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece. PMID: 32395221 PMCID: PMC7202337 DOI: 10.4084/MJHID.2020.032 Free PMC article Abstract Women with sickle cell disease (SCD) are of particular concern regarding the significantly increased risk of pregnancy-related morbidity, mortality, and adverse outcomes. They have limited knowledge of pregnancy and childbirth risks, as well as of the benefits and risks of contraceptives. Thus, there is an urgent need for appropriate information about reproductive family planning to reduce unintended pregnancy. Any decision regarding the use of contraceptives has to be based on the efficacy and risk/benefit ratio of the method used. Both the World Health Organization (WHO) and the Centers for Disease Control (CDC) have developed, published, and updated evidence-based guidelines for medical providers for the use of contraceptives in patients with specific medical chronic conditions. This article provides an overview of the present knowledge on the use of contraceptives in women with SCD. We believe that the collaboration between health care professionals (hematologists, obstetricians, endocrinologists, and primary care providers) can play a major role in identifying the safer contraceptive method to abolish the risks of unintended pregnancy and preserve the health status of patients with SCD. Keywords: Contraception; Pregnancy; Recommendations; Sickle Cell Disease. Conflict of interest statement Competing interests: The authors declare no conflict of Interest. 100 references Publication types Review Full-text links Sickle Cell Trait and The Potential Risk of Severe Coronavirus Disease 2019- A Mini-Review Eur J Haematol. 2020 Jun 26. doi: 10.1111/ejh.13478. Online ahead of print. Authors Tawakalitu Abosede Kehinde  1 Mayowa Azeez Osundiji  2 Abstract Coronavirus Disease 2019 (COVID-19) pandemic is a rapidly evolving public health problem. The severity of COVID-19 cases reported hitherto has varied greatly from asymptomatic to severe pneumonia and thromboembolism with subsequent mortality. An improved understanding of risk factors for adverse clinical outcomes may shed some light on novel personalized approaches to optimize clinical care in vulnerable populations. Emerging trends in the United States suggest possibly higher mortality rates of COVID-19 amongst African Americans, although detailed epidemiological study data is pending. Sickle Cell Disease (SCD) disproportionately affect Black/African Americans in the United States as well as forebearers from sub-Saharan Africa, the Western Hemisphere (South America, the Caribbean, and Central America) and some Mediterranean countries. The carrier frequency for SCD is high amongst African Americans. This article underscores the putative risks that may be associated with COVID-19 pneumonia in sickle cell trait as well as potential opportunities for individualized medical care in the burgeoning era of personalized medicine. Keywords: Acute Chest Syndrome (ACS); Coronavirus Disease 2019 (COVID-19); Sickle Cell Disease (SCD); Sickle Cell Trait; Thromboembolism; Vaso-Occlusive Crisis (VOC).
  Emotional Distress Among Parent Caregivers of Adolescents With Sickle Cell Disease: Association With Patients and Caregivers Variables J Health Psychol. 2020 Jun 26;1359105320935986. doi: 10.1177/1359105320935986. Online ahead of print. Authors Ayodeji A Bioku  1 Jude U Ohaeri  2 Stephen O Oluwaniyi  3 Tinuke O Olagunju  4 Gary A Chaimowitz  4 Andrew T Olagunju  4   5   6 Abstract Evidence suggests that impairment in caregiver wellbeing can alter the quality of care in children with sickle cell disease. We examined 121 parent caregivers of adolescents with sickle cell disease for emotional distress and disruptions to caregiver lifestyle and interests. Participants were predominantly mothers 92(76%) with mean age, 43.59 (SD = 6.39) years. Four in every ten caregivers had emotional distress, and this was predicted by frequent hospital attendance and disruptions in caregiver lifestyle, relationships, and interests. Psychosocial support to promote resilience and adaptive coping-styles to deal with the stress from unforeseen crises, frequent hospital visits, and lifestyle disruptions are indicated to improve caregiver wellbeing. Keywords: adolescents; illness intrusiveness; parent caregivers; psychological distress; psychosocial burden; sickle cell disease.
  Parents of Children With Sickle Cell Disease Are Interested in Preimplantation Genetic Testing J Pediatr. 2020 Jun 22;S0022-3476(20)30471-6. doi: 10.1016/j.jpeds.2020.04.027. Authors Monica Attia  1 Shawn Kripalani  1 Isha Darbari  2 Robert Sheppard Nickel  3 Abstract Objective: To evaluate awareness of and attitudes toward preimplantation genetic testing (PGT) for sickle cell disease (SCD) among parents of children with SCD. Study design: Parents of children with SCD were given an educational handbook on PGT before a routine SCD clinic visit. After their clinic visit, parents were asked to complete an anonymous survey. Results: Of 83 patents approached, 67 (81%) completed the survey. Only 16 of the 67 parents (24%) were previously aware of PGT for SCD. After our clinic-based education, 65 of the 67 parents (97%) indicated that it was important or very important for parents of children with SCD to know about PGT. Among parents interested in having more children, 29 of 32 (91%) would personally consider using PGT if covered by insurance. Conclusions: Parents of children with SCD are generally not aware of PGT. When educated in clinic, parents viewed information on PGT as valuable. Pediatricians and other health care professionals should inform parents of children with SCD about this reproductive option. Keywords: assisted reproductive technology; genetic counseling; preimplantation genetic diagnosis; reproductive choices; sickle cell anemia.
  Red Cell Exchange for Patients With Sickle Cell Disease: An International Survey of Current Practices Transfusion. 2020 Jun 24. doi: 10.1111/trf.15863. Online ahead of print. Authors Matthew S Karafin  1 Jeanne E Hendrickson  2 Haewon C Kim  3 Aisha Kuliya-Gwarzo  4 Monica B Pagano  5 Ajay Perumbeti  6 Patricia A Shi  7 Yvette C Tanhehco  8 Jennifer Webb  9 Edward Wong  9 Quentin Eichbaum  10 Abstract Introduction: Red cell exchange (RCE) therapy is increasingly used to treat patients with acute or chronic manifestations of sickle cell disease (SCD). However, little is known regarding the most safe and effective practice parameters associated with this particular therapy. Methods: A SCD subcommittee of members of the American Society for Apheresis (ASFA) developed a 122-question survey and administered it via email to other ASFA members. The survey inquired about clinical indications for treatment, practice patterns, and transfusion policies for RCE when used for patients with SCD. Results: Ninety-nine distinct institutions completed the survey. Twenty-one (21%) were from outside of the US. Twenty-two (22%) provided chronic transfusion therapy to >10 patients, and both adult (25%) and pediatric-focused services (20%) were represented. Common acute indications for RCE included acute chest syndrome, acute ischemic stroke, and pre-surgical prophylaxis. Common chronic indications included primary stroke prophylaxis, secondary stroke prophylaxis, and recurrent acute chest syndrome. Respondents most commonly set a post-RCE treatment target of 30% for the hematocrit and hemoglobin S levels, regardless of the therapeutic indication. Units for RCE were phenotypically matched in 95% of cases. About 40% of respondents reported using isovolemic hemodilution. Conclusions: This survey solicited the current practice variations in RCE from a diverse range of practice sites. Many sites reported similar practice patterns and challenges but some variations emerged. To our knowledge, this survey represents the largest and most in-depth investigation of the use of RCE for patients with SCD, and could inform future studies in the field. © 2020 AABB. 44 references Full-text links Wiley  
  Management of Hemoglobin Disorders During the COVID-19 Pandemic Front Med (Lausanne). 2020 Jun 9;7:306. doi: 10.3389/fmed.2020.00306. eCollection 2020. Authors Sanjana Fatema Chowdhury  1 Saeed Anwar  2 Free PMC article Abstract The coronavirus disease 2019 (COVID-19) is an emerging infectious disease that has become a global public health concern after being first reported in China and has subsequently spread worldwide. It causes mild to severe respiratory illness with some flu-like symptoms. The causal virus behind this disease, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), conceivably attacks the receptors of the respiratory system of the human body but has no strict evidence of attacking the blood cells yet. However, patients with hemoglobin disorders (e.g., sickle cell anemia, thalassemia) are vulnerable to this global health situation due to their clinical complications. Such patients are generally more prone to viral and bacterial infections, which can worsen their physical condition. Some of these patients present immunocompromised conditions, e.g., splenectomized or post-transplant patients. Therefore, they should follow some preventive steps such as shielding as well as the general guidelines for the COVID-19 pandemic. Transfusion dependent patients require regular monitoring for iron overload, and iron chelation therapy may be stopped by the physician depending on the situation. This article reviews the management strategies and provides some crucial recommendations for people in the corner with hemoglobin disorders. Keywords: COVID-19; SARS-CoV-2; clinical management; hemoglobin; hemoglobinopathies; iron chelation therapy; sickle cell diseases; thalassemia. Copyright © 2020 Chowdhury and Anwar. 40 references Publication types Review Full-text links Frontiers Media SA Free PMC article  
  Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa N Engl J Med. 2020 Jun 25;382(26):2524-2533. doi: 10.1056/NEJMoa2000146. Authors Chandy C John  1 Robert O Opoka  1 Teresa S Latham  1 Heather A Hume  1 Catherine Nabaggala  1 Phillip Kasirye  1 Christopher M Ndugwa  1 Adam Lane  1 Russell E Ware  1 Affiliation Abstract Background: Hydroxyurea has proven safety, feasibility, and efficacy in children with sickle cell anemia in sub-Saharan Africa, with studies showing a reduced incidence of vaso-occlusive events and reduced mortality. Dosing standards remain undetermined, however, and whether escalation to the maximum tolerated dose confers clinical benefits that outweigh treatment-related toxic effects is unknown. Methods: In a randomized, double-blind trial, we compared hydroxyurea at a fixed dose (approximately 20 mg per kilogram of body weight per day) with dose escalation (approximately 30 mg per kilogram per day). The primary outcome was a hemoglobin level of 9.0 g or more per deciliter or a fetal hemoglobin level of 20% or more after 24 months. Secondary outcomes included the incidences of malaria, vaso-occlusive crises, and serious adverse events. Results: Children received hydroxyurea at a fixed dose (94 children; mean [±SD] age, 4.6±1.0 years) or with dose escalation (93 children; mean age, 4.8±0.9 years); the mean doses were 19.2±1.8 mg per kilogram per day and 29.5±3.6 mg per kilogram per day, respectively. The data and safety monitoring board halted the trial when the numbers of clinical events were significantly lower among children receiving escalated dosing than among those receiving a fixed dose. At trial closure, 86% of the children in the dose-escalation group had reached the primary-outcome thresholds, as compared with 37% of the children in the fixed-dose group (P<0.001). Children in the dose-escalation group had fewer sickle cell-related adverse events (incidence rate ratio, 0.43; 95% confidence interval [CI], 0.34 to 0.54), vaso-occlusive pain crises (incidence rate ratio, 0.43; 95% CI, 0.34 to 0.56), cases of acute chest syndrome or pneumonia (incidence rate ratio, 0.27; 95% CI, 0.11 to 0.56), transfusions (incidence rate ratio, 0.30; 95% CI, 0.20 to 0.43), and hospitalizations (incidence rate ratio, 0.21; 95% CI, 0.13 to 0.34). Laboratory-confirmed dose-limiting toxic effects were similar in the two groups, and there were no cases of severe neutropenia or thrombocytopenia. Conclusions: Among children with sickle cell anemia in sub-Saharan Africa, hydroxyurea with dose escalation had superior clinical efficacy to that of fixed-dose hydroxyurea, with equivalent safety. (Funded by the Doris Duke Charitable Foundation and the Cincinnati Children’s Research Foundation; NOHARM MTD ClinicalTrials.gov number, NCT03128515.). Full-text links Atypon  

Meetings for the Sickle Cell Community

2020 Indiana Sickle Cell Conference “Sickle Cell Trait: Taking a Closer Look” The new date September 25th. This one-day Sickle Cell Disease conference will feature educational sessions for healthcare providers, patients/families, and social services providers. The morning sessions will be devoted to healthcare providers and the afternoon sessions will be tailored for patients, family members and social workers.  Medically oriented topics will include improving awareness about Sickle Cell Trait and some of the health complications that research indicates can be associated with it.  Health care providers and others will be presented with information that will broaden current thinking about the prevalence of trait and its impacts on the human body.  Patient oriented topics will include sessions on trait education, including the variant Sickle Cell genotypes and inheritance patterns.  Both sessions are open to the public. All attendees will be provided with information about available resources and current trends in the field.

registration link… https://www.eventbrite.com/e/2020-indiana-sickle-cell-conference-tickets-95286583737

First IASCNAPA Conference 
The International Association of Sickle Cell Nurses and Professional Associates (IASCNAPA) Sickle Cell Conference: Treating the Whole Person scheduled for 4/17/2020 in Memphis is cancelled due to COVID-19 concerns.  The decision to cancel the conference took into account many important factors, including the risk of unnecessary exposure to our patient population. 

The event is rescheduled for April 9, 2021 at the Memphis Hilton. 

Your understanding and support are greatly appreciated! For information go to www.iascnapa.org


Foundation for Sickle Cell Disease Research Symposium 

Due to the unprecedented Novel Coronavirus COVID-19, our annual in-person Symposium is rescheduled to September 23 – 25, 2020.

The Foundation for Sickle Cell Disease Research (FSCDR) is committed to supporting innovative research in sickle cell disease (SCD) to help maximize quality of life and improve survival for the generations of people affected by SCD. The Symposium focuses on interactive education, sharing of best practices, and exploring novel Learn more and register todayhttps://fscdr.org/the-symposium/

NHLBI Annual Sickle Cell Disease Meeting    The National Heart, Lung, and Blood Institute’s (NHLBI) Division of Blood Diseases & Resources’ Annual Sickle Cell Disease (SCD) Meeting will be held virtually beginning on August 10, 2020 and ending on August 12, 2020.  The three-day meeting provides a yearly forum for investigators, practitioners, and interested health care providers to discuss the progress of ongoing clinical trials, hear presentations about new developments in scientific and clinical aspects of SCD, and interact with other investigators and NHLBI Program Staff in an informal setting. To learn more about the meeting and register, please click here.     Virtual Sickle Cell Disease Therapeutics Conference on September 15, 2020    Global Blood Therapeutics (GBT) and the Sickle Cell Disease Association of America (SCDAA) are excited to announce that the 9th Annual Sickle Cell Disease (SCD) Therapeutics Conference (SCDTC) has been scheduled for Tuesday, September 15 starting at 9:00 AM ET.  SCDAA’s President and CEO Beverley Francis-Gibson will host this event virtually.  This annual event convenes key SCD stakeholders focused on discussing issues impacting the community, including the latest advancements and trends in treating sickle cell.  Conference attendees will hear from innovative industry leaders, patients, physicians, community-based organizations and biotech companies.  This year’s moderators include: Dr. Biree Andemariam and Mary Bentley LaMar to name a few. 

This event is open to anyone with an interest in sickle cell and there will be multiple ways to attend!  Sickle Cell Warriors has again exclusively partnered with GBT to livestream the conference via Facebook Live, YouTube, and Sickle Cell Warrior’s website.  To learn more about the SCDTC or to register (U.S. only) visit scdconference.com. #SCDTC.
Save the Date – SCDAA’s 48th Annual National Convention 2020 Is Going Virtual   Given the current uncertainty regarding COVID-19 and its implications for attendee safety and travel, as well as for public health concerns, the Sickle Cell Disease Association of America’s (SCDAA) 48th Annual National Convention is moving to a virtual gathering on October 14-17, 2020.  Clear here for more information.