Sickle Cell Disease: New Insights into Pathophysiology and Treatment

Abstract

<P>Sickle cell disease, the most common monogenetic disorder worldwide affecting an estimated 30 million people, represents a major public health concern because of its associated significant morbidity and mortality. Modern advances in molecular and cellular biology have resulted in an accumulation of data on sickle cell pathophysiology related to erythrocyte and extra-erythrocyte events. These emerging data have broadened our understanding of the complexity of this molecular disease with heterogeneous manifestations and have paved the route to the development of novel and targeted therapeutic interventions. With the increasing scope of knowledge about this disease, it is imperative that pediatricians acquaint themselves with the many clinical presentations and the new insights into pathophysiology and treatment of this disorder.</P><H4>ABOUT THE AUTHORS</H4><P>Adlette Inati, MD, is with Rafik Hariri University Hospital, Division of Pediatric Hematology and Oncology, Beirut, Lebanon, the Chronic Care Center, Hazmieh, Lebanon, and the University of Balamand, Koura, Lebanon. Suzan Koussa, MD, is with the Chronic Care Center, Hazmieh. Ali Taher, MD, is with the American University of Beirut Medical Center, Department of Internal Medicine, and Chronic Care Center, Hazmieh. Susan Perrine, MD, is with the Boston University School of Medicine, Boston, Massachusetts.</P><P>Address correspondence to: Adlette Inati, MD, Division of Pediatric Hematology Oncology, Children’s Center for Cancer and Blood Diseases, Rafik Hariri University Hospital, Beirut, Lebanon; or e-mail <a href="mailto:khorina@dm.net.lb">khorina@dm.net.lb</a>.</P><P>Dr. Inati, Dr. Koussa, and Dr. Taher have disclosed no relevant financial relationships. Dr. Perrine has disclosed the following relevant financial relationships: HemaQuest Pharmaceuticals: Employee/stockholder. </P><H4>EDUCATIONAL OBJECTIVES</H4><OL><LI>Discuss the current pathophysiologic model of sickle cell disease and genotype-phenotype correlation.</LI><LI>Describe the predictors of disease severity and identify reasons for improved survival.</LI><LI>Review disease-modifying therapies and understand the mechanism of action of novel targeted treatments.</LI></OL>