Beyond the Definitions of the Phenotypic Complications of Sickle Cell Disease: An Update on Management

1. Introduction

Sickle cell disease (SCD) is an inherited chronic hematological disorder that has no established cure to date except in a few patients who had successful bone marrow or stem cell transplantation. Although gene therapy for sickle cell anemia, the ultimate goal of cure, is not feasible at the present, significant strides have been made at the basic level to achieve the genetic correction of hemoglobinopathies [1]. The molecular lesion of the sickle hemoglobin is a point mutation ( $\text{GAG}\to \text{GTG}$ ) in exon 1 of the $\beta$ globin gene resulting in the substitution of glutamic acid by valine at position 6 of the $\beta$ globin polypeptide chain [2, 3]. This single-point mutation renders the sickle gene pleiotropic in nature with multiple phenotypic expressions associated with complex genetic interactions and modifiers that are not well understood [2, 3]. The complications of this disease are numerous and affect every organ and/or tissue in the body. Recently concise definitions of these complications have been published [4] thus creating a uniform understanding of the nature of these complications among providers, researchers, patients and their families, and the community at large. The definition of each complication was based on published evidence if available and/or on the experience of experts in the field. The definitions also included the diagnostic criteria, severity index, and classification of each complication whenever available. Specific management and treatment of these complications, however, were not described.

The purpose of this paper is to briefly update the definitions by including newly described complications and review the accepted approaches for the management and treatment of the major complications of sickle cell disease. These will be based on published evidence if available and on the experience of experts in the field. To that end management of pain syndromes, hematological, neurological, ophthalmological, pulmonary, hepatobiliary, splenic, renal, genitourinary, musculoskeletal, and dermatological complications will be addressed. Recently, there has been increasing evidence that asthma predisposes to certain complications of sickle cell disease including acute painful crises, acute chest syndrome, pulmonary hypertension and stroke [5]. Management of comorbid conditions, however, will not be addressed except in certain situations where the comorbid condition has a direct effect on the manifestation and management of the sickle cell complication in question. It is hoped...

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