Red blood cells develop in the bone marrow, which is the sponge-like tissue inside your bones. Your body normally destroys old or faulty red blood cells in the spleen or other parts of your body through a process called hemolysis. Hemolytic anemia occurs when you have a low number of red blood cells due to too much hemolysis in the body. There are many types of hemolytic anemia, which doctors diagnose based on the underlying cause of your anemia. Certain conditions can cause hemolysis to happen too fast or too often. Conditions that may lead to hemolytic anemia include inherited blood disorders such as sickle cell disease or thalassemia, autoimmune disorders, bone marrow failure, or infections. Some medicines or side effects to blood transfusions may cause hemolytic anemia. Abstract source

Nearly 7 decades have passed since seminal studies of hemoglobin led to the characterization of sickle cell anemia as the first defined molecular disease. These foundational insights into sickle cell disease (SCD) initiated an exciting era of medicine that has substantially expanded the understanding of the molecular basis of thousands of disorders over the ensuing years. The field of molecular medicine is now at a pivotal moment in its history, a time when scientific capabilities to read, edit, and reprogram the human genetic code for therapeutic approaches are within reach. The rapid pace of innovation in emerging technologies of gene editing and translational research suggest that it is time to accelerate curative therapies for the first defined molecular disease. Abstract source

Sickle-cell anaemia (SCA) is a neglected chronic disorder of increasing global health importance, with India estimated to have the second highest burden of the disease. In the country, SCA is particularly prevalent in scheduled populations, which comprise the most socioeconomically disadvantaged communities. We compiled a geodatabase of a substantial number of SCA surveys carried out in India over the last decade. Using generalised additive models and bootstrapping methods, we generated the first India-specific model-based map of sickle-cell allele frequency which accounts for the district-level distribution of scheduled and non-scheduled populations. Where possible, we derived state- and district-level estimates of the number of SCA newborns in 2020 in the two groups. Through the inclusion of an additional 158 data points and 1.3 million individuals, we considerably increased the amount of data in our mapping evidence-base compared to previous studies. Highest predicted frequencies of up to 10% spanned central India, whilst a hotspot of ~12% was observed in Jammu and Kashmir. Evidence was heavily biased towards scheduled populations and remained limited for non-scheduled populations, which can lead to considerable uncertainties in newborn estimates at national and state level. This has important implications for health policy and planning. By taking population composition into account, we have generated maps and estimates that better reflect the complex epidemiology of SCA in India and in turn provide more reliable estimates of its burden in the vast country. Abstract source

Sickle cell disease (SCD) is a collective name for a series of serious inherited chronic conditions that can affect all systems of the body. It is one of the most common genetic conditions in the world, but is considered a rare disease in the US. Sickle cell disease is associated with episodes of severe pain called sickle cell painful crises. The School’s Role Sickle cell is not a benign illness and requires life long medical care. Students will have complications that will inevitably show up at school or affect their attendance. It is very important that all school staff that interact with the student not only understand the severity of the illness, but feel confident in how to handle possible complications. Although your student has a chronic illness, it is also your role to help them feel safe, normal, and loved. They are more than SCD and want to be treated just like everyone else whnever possible.   Abstract source

Define yourself, define your life. No matter how old you are or how severe your sickle cell disease is, you can start where you are and learn more about sickle cell disease. The more you know, the more options you have and more options exist now than ever before. Advances are being made, and there is hope. This booklet was inspired, designed and created by your brothers and sisters in the sickle cell community to encourage, uplift and inform you. We want you to know you are not alone. Sickle cell is part of our lives, but it does not define us and it cannot break us. Join us as we redefine what it means to live with sickle cell.   Abstract source

Background: Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with severe morbidity, impaired quality of life, and premature mortality. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for patients with SCD and has a >90% event-free survival when a matched related donor is used. However, availability of human leukocyte antigen (HLA)-identical sibling donors for the SCD population is limited. The use of HLA-matched unrelated donors or related haploidentical donors has the potential to expand the donor pool. Methods: We reviewed the current literature on the indications for SCD transplantation, donor options, and the emerging use of gene therapy as a treatment option. Google Scholar and PubMed were searched using the terms SCD, bone marrow transplantation, donor sources, gene therapy, HSCT, and HLA matching. Additional articles were identified from the bibliographies of retrieved articles. All articles were reviewed for pertinent information related to SCD and transplantation. Results: HSCT has the potential to establish donor-derived normal erythropoiesis with stable long-term engraftment, amelioration of symptoms, and stabilization of organ damage. The majority of HSCT has been performed in children from HLA-identical sibling donors and has resulted in excellent rates of survival. The use of alternate donors such as HLA-matched unrelated donors and haploidentical donors has the potential to expand the applicability of HSCT for SCD. Early results in gene therapy for SCD are encouraging. Conclusion: Evaluation of the long-term benefits of curative therapies for SCD requires comparative clinical trials and studies of late effects. Abstract source Full text

Dr. Ambrusko is a pediatric hematologist/oncologist with a clinical focus on sickle cell disease at Roswell Park Oishei Children’s Hospital. He is the Director of the Sickle Cell & Hemoglobinopathy Center of Western New York, caring for children and adolescents with sickle cell disease, thalassemias, porphyrias, and other hemoglobin disorders. In this role, his focus is on improving patient outcomes, decreasing sickle cell disease related complications, and program development, including community outreach. Dr. Ambrusko earned his medical degree from School of Medicine and Biomedical Sciences, State University of New York at Buffalo and completed his residency at the State University of New York and fellowship from Children’s Hospital Pittsburgh (Pediatric Hematology/Oncology) University Health Center of Pittsburgh. He is also available on an outpatient consultative basis for adults with sickle cell disease / hemoglobinopathies in the community.   Representative Publications: Elevation of Tricuspid Regurgitant Jet Velocity, a Marker for Pulmonary Hypertension in Children With Sickle Cell Disease Successful Management of Refractory Haematuria With Recombinant Porcine Factor VIII Replacement for Paediatric Congenital Haemophilia a With High-Titre Inhibitor Online profile

Sickle cell disease (SCD) is one of the most common severe genetic diseases around the world. A majority of SCD patients experience intense pain, leading to hospitalization, and poor quality of life. Opioids form the bedrock of pain management, but their long-term use is associated with severe side effects including hyperalgesia, tolerance and addiction. Recently, excellent research has shown some new potential mechanisms that underlie SCD-associated pain. This review focused on how transient receptor potential vanilloid 1, endothelin-1/endothelin type A receptor, and cannabinoid receptors contributed to the pathophysiology of SCD-associated pain. Understanding these mechanisms may open a new avenue in managing SCD-associated pain and improving quality of life for SCD patients. Abstract source

Background: High Immunoglobulin G (IgG) response to Plasmodium falciparum antigens is associated with partial malaria protection in sickle hemoglobin (HbS) children. However, this response has been more studied in children with heterozygous sickle cell trait (HbAS) but little explored in those with homozygous sickle cell trait (HbSS). The current study was conducted to determine the IgG responses against specific Plasmodium falciparum antigens in children with homozygous sickle cell trait (HbSS) by comparing to those with normal hemoglobin (HbAA). Methods: A cross sectional study was conducted between April and July 2018 in Dar es Salaam tertiary hospitals. Parents were consented for their child to give about 5 ml of venous blood. IgG concentration from the blood plasma of 220 children (110 HbAA vs. 110 HbSS) were determined using indirect Enzyme Linked Immunosorbent Assay (ELISA). Then IgG medians were compared between the groups with prism 5 software (GraphPad) using Mann Whitney U test. Where the differences in age, hemoglobin levels and body weight between the groups was analyzed using independent sample t test. Multiple linear regressions were used to control cofounding variables such as body weight, age and hemoglobin level using statistical package for social sciences software (SPSS version 23). P value <0.05 was considered statistically significant. Results: The median IgG concentration to PfEBA-175, Pfg27, yPfs28C antigens were HbSS; 20.7 ng/ml (IQR; 18.1-25.6) vs. HbAA; 2.3 ng/ml (IQR; 1.21-3.04), HbSS; 2.76 ng/ml (IQR: 2.08-5.69) vs. HbAA; 1.36 ng/ml (IQR: 1.28-1.76), and HbSS; 26,592 ng/ml (IQR: 10817-41,462) vs. HbAA; 14,164 ng/ml (IQR; 3069-24,302) respectively (p < 0.0001 for all IgG). In both groups; age, body weight and hemoglobin level had no impact on the levels of IgG responses to Plasmodium falciparum antigens except for HbAA group which showed a significant increase in IgG against Pfg27 by 0.004 ng/ml with 1 g/dl increase in Hb level (p = 0.028). Conclusions: This study found significant higher levels of specific Plasmodium falciparum IgG responses in children with homozygous sickle cell trait than those with normal hemoglobin. Abstract source Full text

Haploidentical hematopoietic stem cell transplantation (HSCT) from partially matched first-degree relatives (e.g., parent, sibling, child) is the newest therapy available to reverse symptoms of adults with sickle cell disease. Because of this innovation, little is known about the recipients' transplant experiences and how this type of transplant affects their quality of life. We describe the experiences and health-related quality of life (HRQOL) of five (3 female, 2 male) of nine eligible adults with sickle cell disease who received HSCT. Participants completed a brief demographics form, an HRQOL survey, and a 90-minute audio-recorded interview. We produced a series of matrices and summaries for our content analysis in addition to descriptive statistics. We report on recipients' perspectives about the process, outcomes, personal life goals, and how their experience relates to their HRQOL scores. Participants' impressions of their experience varied, but their HRQOL scores paralleled their complications. Those with successful transplants and minimal complications scored highest. Those with successful transplants but significant complications scored in the middle and the individual with an unsuccessful transplant scored the lowest. The four with successful transplants remarked that their health had improved and expressed optimism. We identified three themes: (a) the relief of being pain free, (b) new availability of opportunities, and (c) no regrets about undergoing the transplant. These results delve into the complex factors affecting health and the success of adults with SCD who have a haploidentical HSCT. Abstract source