Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD (∼100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype–phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed. Am. J. Hematol. 2010.

The acute sickle cell painful episode is the most common cause of hospitalization of patients with sickle cell anemia. Its detailed clinical features and peri-discharge features are not well known. In order to determine the actual pattern of hospital admissions of patients with SS and the causes of frequent hospital readmissions and their prognostic significance, we conducted a prospective longitudinal and observation cohort study of all adult patients with sickle cell anemia admitted to Thomas Jefferson University Hospital between January 1998 and December 2002. Major outcome measures included the frequency, etiology, and prognostic significance of readmissions to the hospital within 1 week and 1 month after discharge. Incidence of mortality among patients during the study period was also determined. Analysis of the data showed that about 50% of hospital admissions for acute painful episodes were readmitted within 1 month after discharge, and about 16% of all admissions were within 1 week after discharge. The intensity of pain score decreased significantly during the first 4 days of hospital admission (P < 0.001) and then reached a plateau until discharge. The mean score of pain intensity was >7 throughout the hospital stay. Causes of hospital readmission included premature discharge, withdrawal syndrome, and recurrence of new acute episodes. Readmission within 1 week after discharge was associated with higher mortality than otherwise. This study shows that hospital readmission of adult patients with sickle cell anemia is common. It suggests that improvement is needed in the management of pain during hospitalization and at home after discharge. Patients who are readmitted frequently within 1 week of discharge have poor prognosis and require careful monitoring. Am. J. Hematol. 79:17–25, 2005.

Early diagnosis, treatment, and prevention of a vaso‐occlusive crisis (VOC) are critical to the management of patients with sickle cell disease. It is essential to differentiate between VOC‐associated pain and chronic pain, hyperalgesia, neuropathy, and neuropathic pain. The pathophysiology of VOCs includes polymerization of abnormal sickle hemoglobin, inflammation, and adhesion. Hydroxyurea, L‐glutamine, crizanlizumab, and voxelotor have been approved by the US Food and Drug Administration for reducing the frequency of VOCs; the European Medicines Agency has approved only hydroxyurea. Other novel treatments are in late‐stage clinical development in both the United States and the European Union. The development of agents for prevention and treatment of VOCs should be driven by our understanding of its pathophysiology.

The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of theβglobin gene resulting in the substitution of glutamic acid by valine at position 6 of theβglobin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals.