Sickle cell disease is characterized by unpredictable episodes of extreme pain, known as acute vaso-occlusive episodes (VOE) or pain episodes, caused when sickled red blood cells are unable to move freely through blood vessels. In addition to pain, these changes at the cellular level can also lead to organ damage, stroke and even death. Pain episodes are the most common reason for emergency department (ED) visits and hospitalizations for patients with sickle cell disease. Detailed guidelines and quality indicators for the management of pain episodes currently exist, but both pediatric and adult patients with the disease often experience prolonged periods of waiting for treatment in the emergency department and ineffective treatment of their pain. Delays in treatment are often due to systemic factors, such as the lack of a clear treatment protocol or limited provider experience in treating sickle cell diseaserelated pain. Prolonged waits for effective pain relief can lead to unnecessary suffering, hospitalizations, chronic pain syndromes, other complications and increased health care costs.1,8,10-12 Ensuring patients receive timely, effective pain relief is one of the most important elements of delivering high quality care to individuals with sickle cell disease in the emergency department.   Abstract source

Pulmonary hypertension affects ∼10% of adult patients with sickle cell disease (SCD), particularly those with the homozygous genotype. An increase in pulmonary artery systolic pressure, estimated noninvasively by echocardiography, helps identify SCD patients at risk for pulmonary hypertension, but definitive diagnosis requires right-heart catheterization. About half of SCD-related pulmonary hypertension patients have precapillary pulmonary hypertension with potential etiologies of (1) a nitric oxide deficiency state and vasculopathy consequent to intravascular hemolysis, (2) chronic pulmonary thromboembolism, or (3) upregulated hypoxic responses secondary to anemia, low O2 saturation, and microvascular obstruction. The remainder have postcapillary pulmonary hypertension secondary to left ventricular dysfunction. Although the pulmonary artery pressure in SCD patients with pulmonary hypertension is only moderately elevated, they have a markedly higher risk of death than patients without pulmonary hypertension. Guidelines for diagnosis and management of SCD-related pulmonary hypertension were published recently by the American Thoracic Society. Management of adults with sickle-related pulmonary hypertension is based on anticoagulation for those with thromboembolism; oxygen therapy for those with low oxygen saturation; treatment of left ventricular failure in those with postcapillary pulmonary hypertension; and hydroxyurea or transfusions to raise the hemoglobin concentration, reduce hemolysis, and prevent vaso-occlusive events that cause additional increases in pulmonary pressure. Randomized trials have not identified drugs to lower pulmonary pressure in SCD patients with precapillary pulmonary hypertension. Patients with hemodynamics of pulmonary arterial hypertension should be referred to specialized centers and considered for treatments known to be effective in other forms of pulmonary arterial hypertension. There have been reports that some of these treatments improve SCD-related pulmonary hypertension. Abstract source Full text

Despite a long history of knowing the genetic cause of sickle cell disease (SCD), progress in developing treatments to prevent painful vaso-occlusive crises and the other myriad of associated symptoms has, until recently, been disappointingly slow. As long ago as 1949, Pauling et al described sickle cell anemia as a molecular disease, with two other groups convincingly describing it as an inherited disorder. Details of the mutation (replacement of glutamic acid with valine in the 6th position of the hemoglobin [Hb] β-chain) were first described by Ingram in 1956. Despite these early discoveries, the life expectancy of sickle cell patients only began to improve significantly within the last 30 years, first with the introduction of prophylactic penicillin V in the 1980s, followed by more aggressive blood transfusions, and in 1998, with the introduction of hydroxyurea as a mainstay of treatment. Beyond the mutation of Hb as the cause of SCD, Hebbel et al initiated a new era of research in 1980 by introducing the concept that sickle red blood cells (RBCs) are abnormally adhesive. Many subsequent studies from Hebbel et al and others led to the realization that not only sickle RBCs but other blood cells, especially leukocytes and platelets, are activated and have the potential to contribute to vaso-occlusive crises. This is a backdrop for the current review series. Over the last few years, our understanding of the complexities of cellular, plasma, and genetic contributors to the various symptoms of SCD has accelerated. New drugs and genetic cures are on the horizon. In this review series, five leading groups provide updates on important aspects of SCD. Abstract source

Brenda Martin is a pediatric nurse practitioner at Children’s National Medical Center (CNMC). As a Research Coordinator, she contributes to the sickle cell community to promote quality care through research. She received her undergraduate degree (BSN) from Hunter College in 1977 and her Masters in Nursing (MSN) from Columbia State University in New York City in 1995. As a clinician, Brenda has provided comprehensive care to children with sickle cell disease and focuses on helping sickle cell children with chronic pain. She also advocates for research participation to promote state of the art care. As a research investigator, Brenda has participated in several NIH grants: TWICTH-Transfusions changing to Hydroxyurea, STOP - Stroke Prevention in Sickle Cell, Baby Hug- Hydroxyurea in very young children with sickle cell anemia and Neurodevelopmental Deficits among Infants with Sickle Cell Disease. Brenda is a part of Integrative Sickle Cell Pain Clinic, where sickle cell patients are treated with non-pharmacological interventions. She has co-authored several publications and presented at numerous conferences on sickle cell disease.   Representative Publications: Views of parents of children with sickle cell disease on pre-implantation genetic diagnosis Neurodevelopmental deficits among infants and toddlers with sickle cell disease Online profile

Dr. Ogu currently serves as an Assistant Professor (Medicine-Hematology) at The University of Tennessee Health Science Center. Prior to this, she was associated with the Albert Einstein College of Medicine as an Assistant Professor of Clinical Medicine and Pediatrics. She obtained her medical degree at Windsor University School of Medicine in the West Indies, completed residency in Pediatrics at the University of Iowa, and fellowship in Pediatric Hematology-Oncology at Memorial Sloan Kettering Cancer Center/New York Presbyterian Hospital-Weill Cornell Medicine. Her clinical interest focuses on sickle cell disease and transition of care from pediatrics to adult. Dr. Ogu was also associated with the Division of Hematology at Montefiore as the Assistant Director of the Sickle Cell Center for Adults.   Representative Publications: Comorbidities in sickle cell disease: Adult providers needed! Reduced blood pressure of CFTR-F508del carriers correlates with diminished arterial reactivity rather than circulating blood volume in mice Successful Management of Blue Rubber Bleb Nevus Syndrome (BRBNS) with Sirolimus Online profile

Daniel E. Bauer is currently engaged as principal faculty at Harvard Stem Cell Institute. His research interests primarily consist of blood diseases and cancer. Dr. Bauer graduated from Brown University with a BS in Biology. He received an MD and PhD from the University of Pennsylvania. His PhD in Cell and Molecular Biology was under the mentorship of Craig Thompson, investigating mechanisms of growth factor regulation of hematopoietic cell metabolism. Dr. Bauer trained in pediatrics and pediatric hematology/oncology at Boston Children’s Hospital and Dana-Farber Cancer Institute. His postdoctoral work was in the laboratory of Stuart Orkin, MD, where he studied the role of common genetic variation in the regulation of fetal hemoglobin. Dr. Bauer is also an Attending Physician at Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Assistant Professor in Pediatrics, Harvard Medical School. His laboratory studies the genetic determinants of blood cell ontogeny and disease. They use molecular genetic, biochemical, and genome editing methodologies to perturb and observe blood cells. His aim is to apply their discoveries to develop novel treatment strategies for blood disorders.   Representative Publications: Emerging Genetic Therapy for Sickle Cell Disease Curative approaches for sickle cell disease: A review of allogeneic and autologous strategies Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease Online profile

Allistair Abraham is currently affiliated with Children’s National Health System as blood and marrow transplantation specialist. He is engaged with various other departments of the main hospital such as center for cancer and blood disorders, oncology, comprehensive sickle cell disease program, blood and marrow transplant and blood disorders department. His clinical specialities include allogeneic blood and marrow transplantation, blood and marrow transplant for sickle cell disease, bone marrow transplant, infant sickle cell program, sickle cell disease and thalassemia. Dr. Abraham obtained his medical degree from Georgetown University School of Medicine. He completed his residency from Jackson Memorial Hospital followed by fellowship in pediatric hematology/oncology and pediatric bone marrow transplant from St. Jude Children's Research Hospital.   Representative Publications: Alternative Donor/Unrelated Donor Transplants for the β-Thalassemia and Sickle Cell Disease Relationship between Mixed Donor-Recipient Chimerism and Disease Recurrence after Hematopoietic Cell Transplantation for Sickle Cell Disease Clinical risks and healthcare utilization of hematopoietic cell transplantation for sickle cell disease in the USA using merged databases Unrelated Umbilical Cord Blood Transplantation for Sickle Cell Disease Following Reduced-Intensity Conditioning: Results of a Phase I Trial A trial of unrelated donor marrow transplantation for children with severe sickle cell disease Online profile