Dr. Reeves’ research is focused on improving the delivery of preventive care to children with chronic conditions. This work includes identifying opportunities for improvement for recommended preventive care among children with sickle cell disease, such as receipt of transcranial Doppler screening, appropriate antibiotic prophylaxis, and use of hydroxyurea therapy. She also partnered with the Michigan Department of Health and Human Services to identify children with sickle cell trait in Michigan, as well as any negative health related consequences associated with this carrier status. In addition, Dr. Reeves is active in collaboration with the Quality Measurement, Evaluation, Testing, Review, and Implementation Consortium (Q-METRIC) to assess the quality of care provided to children with chronic condition such as sickle cell disease and asthma. Online profile

Blood transfusion in the management of sickle cell disease (SCD) can be lifesaving and reduces disability. However, it may cause morbidity, including alloimmunisation and iron overload (Ballas 2001, Darbari, et al 2006, Rosse, et al 1990, Vichinsky, et al 1990), and mortality (Royal and Seeler 1978, Serjeant 2003). A paucity of randomised controlled clinical trials has resulted in wide variations in clinical practice. However, recent randomised studies have addressed some of the outstanding issues around indications to prevent some chronic complications (DeBaun, et al 2014) and to prevent perioperative acute complications, such as acute chest syndrome (Howard, et al 2013). We have reviewed the evidence and developed two linked guidelines on transfusion in SCD; Part I relates to general principles and laboratory aspects, whereas Part II addresses indications for transfusion in sickle cell disease. Here the term sickle cell disease refers to all genotypes of the disease and sickle cell anaemia to the homozygous state (SS). Abstract source

Red cell transfusion has an important role in the management of sickle cell disease (SCD) in both emergency and elective settings. However, because of insufficient randomised data, it is not always clear when or how to use red cell transfusion. A companion guideline, Guidelines on red cell transfusion in sickle cell disease Part I: principles and laboratory aspects, addresses the general principles of transfusion practice in SCD (Davis et al, BJH in press). The present guideline examines current available evidence on indications for transfusion in SCD. This may not be appropriate for all clinical scenarios and clinical decisions must be based on individual patient considerations. In both guidelines, the term sickle cell disease refers to all genotypes of the disease, and sickle cell anaemia to the homozygous state (SS). Abstract source

Dr. Lakiea Bailey is a sickle cell disease advocate, educator, research scientist, and is the Executive Director of the Sickle Cell Community Consortium.  Diagnosed with sickle cell disease at age three, she has become a passionate advocate for those living with rare diseases and is committed to serving as a voice of encouragement and empowerment within the sickle cell community. Dr. Bailey earned a Bachelor degree in Biochemistry and Molecular Biology in 2001 and a Doctorate degree in Molecular Hematology and Regenerative Medicine in 2012.  During the course of her education, she was named a Doctoral Scholar with the Southern Regional Education Board (SREB), was the recipient of multiple honors and awards, including the Fisher Scientific Award for Overall Excellence in Biomedical Research, the Medical College of Georgia Alumni Association Award, the Georgia Reagents University Leadership Award and was inducted in the Alpha Upsilon Phi honor society.  Dr. Bailey believes that through hard work, diligence, patience and faith, even the seemingly most impossible obstacles can be overcome.  Her story has been featured by StoryCorps, NHLBI, Global Genes, Sickle Cell Warriors, Inc., Patient Worthy, LA Talk Live, and other media outlets.  Her research has been published in numerous peer-reviewed journals and she is honored to have been the recipient of multiple community advocacy awards and recognitions. In addition to serving as the Executive Director of the Sickle Cell Community Consortium, a coordinated network of sickle cell community-based organizations (CBOs), patient and caregiver advocates, community partners and healthcare/research advisors, Dr. Bailey is a contract consultant, sickle cell disease and patient engagement expert with many companies and organizations, sits on the Research Advisory Board for the Foundation for Sickle Cell Disease Research and serves as an editor for the Journal of Sickle Cell Disease and Hemoglobinopathies.  Dr. Bailey enjoys traveling across the nation promoting sickle cell awareness.  Her goal is to provide a platform to harness and amplify the power of the patient voice, ensuring that the sickle cell patient and caregiver takes a leadership role in research, policy, advocacy, legislation and education. Online profile

Existing evidence reviews on newborn blood spot screening (for example, health technology assessments, systematic reviews, literature synthesis) are outdated and/or have not assessed the long-term health consequences or health economic impact on the health system. Further, the transferability of the evidence base to the Alberta setting is uncertain, as the value in terms of both health outcomes and costs are ultimately dependent on local epidemiology, clinical practice, system capacity, and costs. Accordingly, there was a need to conduct an updated evidence assessment contextualized to the Alberta setting. There are seven conditions that are not currently primary targets for screening or secondary conditions identified via screening in Alberta that are widely represented in or being considered for screening programs in many jurisdictions across North America: galactosemia (GALT); tyrosinemia type I (TYRI); homocystinuria (HCY); sickle cell anemia (Hb SS), sickle cell/beta-thalassemia (Hb S/β-thal), and sickle cell/hemoglobin C disease (Hb SC) (hemoglobinopathies collectively referred to here as sickle cell disease [SCD]); and severe combined immunodeficiency (SCID). As such, this evidence assessment focuses on these seven conditions and the associated tests used to identify them, to assess the potential health economic impact of adding any or all of these conditions to the Alberta Newborn Metabolic Screening (NMS) Program. Abstract source

Sickle cell disease (SCD) is a multisystem disease, associated with episodes of acute illness and progressive organ damage. Despite its low prevalence in the United States, SCD is one of the most common severe monogenic disorders worldwide, with an estimated 230,000 affected children born every year in sub-Saharan Africa. As a result of its multiple complications, SCD is associated with an overall decreased life expectancy. In addition, the economic burden of SCD is enormous - a consequence of recurrent and chronic SCD-related complications, frequent absences from school and work, and physical impairment limiting the ability to contribute to society. Although there is an increased understanding of the pathophysiology of SCD, available pharmacologic treatments remain limited. The current approach to the management of SCD includes supportive treatments with folic acid; symptomatic treatment with analgesics, intravenous fluids, oxygen and red blood cell (RBC) transfusion; disease-modifying treatment with hydroxyurea and RBC transfusion; and curative therapy with bone marrow transplantation. Despite the success of bone marrow transplantation as a curative approach in SCD, this modality is limited by its high cost, decreased availability of suitable donors and toxicity. Abstract source

While an orphan disease in the USA, sickle cell disease (SCD), a group of genetic disorders of hemoglobin structure and function, is a major public health problem in much of the rest of the world, particularly sub-Saharan Africa. The pathophysiology of SCD stems from the formation of sickle hemoglobin polymers that deform the erythrocyte into a characteristic sickle shape, the rapidity of which is regulated by its intracellular hemoglobin concentration. Subsequent vaso-occlusion is dependent on adhesion of sickled erythrocytes, and perhaps other cellular elements, including leucocytes and platelets, to abnormal vascular endothelium using a number of receptor–ligand pairs. This propensity for vaso-occlusion may be enhanced by altered vascular tone from excessive amounts of vaso-constrictive factors or diminished amounts of vasodilatory factors. Acute pain is the hallmark symptom caused by sickle polymer formation and subsequent vaso-occlusion, and is represented in the endpoints of most previous and current clinical trial designs. Numerous failures of prior investigational agents have frustrated clinicians and patients alike. Hydroxyurea is currently the only US Food and Drug Administration-approved drug for SCD and reduces the frequency of vaso-occlusive complications in many individuals. A considerable therapeutic need remains as hydroxyurea usage is currently not approved for all types of SCD, is not always clinically effective, and requires frequent monitoring. Recent improvements in our understanding of SCD pathophysiology have generated many new therapeutic targets and associated investigational agents. For example, a number of more specific fetal hemoglobin inducers and several therapies to reduce sickle polymer formation are being tested in preclinical and early phase clinical trials. Several agents that target receptor–ligand interactions which mediate cellular adhesion to vascular endothelium have shown considerable promise and are entering Phase III trials, but present some continuing challenges in clinical trial design and conduct. Gene therapy trials are poised to start and offer the potential for curative therapy. Abstract source Full text

Despite Food and Drug Administration (FDA) approval of hydroxyurea to reduce the frequency of vaso-occlusive episodes, sickle cell disease (SCD) has continued to be treated primarily with analgesics for pain relief. However, elucidation of the multiple pathophysiologic mechanisms leading to vaso-occlusion and tissue injury in SCD has now resulted in a burgeoning effort to identify new treatment modalities to prevent or ameliorate the consequences of the disease. Development of new drugs as well as investigation of drugs previously used in other settings have targeted cell adhesion, inflammatory pathways, upregulation of hemoglobin F, hemoglobin polymerization and sickling, coagulation, and platelet activation. Although these efforts have not yet yielded drugs ready for FDA approval, several early studies have been extremely encouraging. Moreover, the marked increase in clinical pharmaceutical research addressing SCD and the new and old drugs in the pipeline make it reasonable to expect that we will soon have new treatments for SCD. Abstract source Full text Full text (PMC)

In sickle-cell disease, a point mutation in the β-globin chain causes haemoglobin to polymerise within erythrocytes during deoxygenation, altering red blood cell rheology and causing haemolysis. Improvements in health infrastructure, preventive care, and clinical treatments have reduced the morbidity and mortality of sickle-cell disease in developed countries. However, as these patients live longer, the chronic effects of sustained haemolytic anaemia and episodic vaso-occlusive events drive the development of end-organ complications. Cardiopulmonary organ dysfunction and chronic kidney injury have a large effect on morbidity and premature mortality, and typically accelerate in the second decade of life. These processes culminate in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, and sudden death. In this Series paper, we review the mechanisms, clinical features, and epidemiology of major cardiovascular complications in patients with sickle-cell disease and discuss how screening and intervention could reduce their incidence. Abstract source Full text

Sickle-cell disease affects millions of individuals worldwide, but the global incidence is concentrated in Africa. The burden of sickle-cell disease is expected to continue to rise over the coming decades, adding to stress on the health infrastructures of many countries. Although the molecular cause of sickle-cell disease has been known for more than half a century, treatment options remain greatly limited. Allogeneic haemopoietic stem-cell transplantation is the only existing cure but is limited to specialised clinical centres and remains inaccessible for most patients. Induction of fetal haemoglobin production is a promising strategy for the treatment of sickle-cell disease. In this Series paper, we review scientific breakthroughs in epidemiology, genetics, and molecular biology that have brought reactivation of fetal haemoglobin to the forefront of sickle-cell disease research. Improved knowledge of the regulation of fetal haemoglobin production in human beings and the development of genome editing technology now support the design of innovative therapies for sickle-cell disease that are based on fetal haemoglobin. Abstract source Full text