Haema 2013; 4(1):78-89
by Ekaterini Megalakaki1, Maria Stamouli2
1Department of Hematology, Metaxa Hospital, Piraeus, Greece,
22nd Department of Internal Medicine Propaedeutic, Attikon University Hospital, Haidari, Greece
Abstract
Sickle cell disease (SCD) is one of the most frequent hemoglobinopathies worldwide and the first inherited disorder to be studied at the molecular level. SCD is characterized by the presence of hemoglobin S (HbS). HbS tends to polymerize and deform red blood cells into an irreversible sickle shape. SCD affects multiple organs. Its primary manifestations are hemolysis, vasoocclusion and sus- ceptibility to infection. As has been demonstrated in recent years, pathophysiology of the disease, in addition to sickling of red blood cells and vascular occlusion, also includes red cell dehydration, chronic nitric oxide depletion, inflammation and endothelial dysfunction. Diagnosis is established by hemoglobin electrophoresis. Prenatal diagnosis is available through direct detection of the mutation responsible for SCD. SCD has long been known to have a remarkably variable clinical course. Its heterogeneity could be attributed to genetic polymorphisms, a hypothesis that is currently under investigation. The complications of SCD involve many organs and appear very early in life. Hemolytic anemia, aplastic episodes, painful crises and vasoocclusive phenomena gradually lead to organ dysfunction which is often severe. Hydroxycarbamide is known to increase ηbF percentage and protects red blood cells from ηbS polymerization. It has been demonstrated in many studies that hydroxycarbamide improves the clinical course of the disease. At the same time, new knowledge concerning the pathophysiology of SCD has given way to many new agents that are currently under investigation for therapeutic use. For the moment allogeneic hemopoietic stem cell transplantation (though not available or appropriate for all patients) is the only curative approach while gene therapy is still the object of intensive research. Early diagnosis and counseling of both the patient and its family, including immunizations and prophylaxis with penicillin, have significantly improved life expectancy as well as quality of life.