Acute Chest Syndrome in Sickle Cell

Acute chest syndrome (ACS) is the leading cause of death and the second most common reason for hospitalization in patients with sickle cell disease (SCD). It is defined as a new pulmonary infiltrate on chest radiograph involving at least one complete lung segment, accompanied by one or more of the following: fever (temperature above 38.5 degrees Celsius), respiratory symptoms (cough, dyspnea, tachypnea, chest pain), or hypoxemia. Understanding the complex pathophysiology of ACS requires a thorough knowledge of sickle cell hemoglobin polymerization, vaso-occlusion, and the interplay between infection, fat embolism, and pulmonary vascular dysfunction. Sickle cell disease results from a point mutation in the beta-globin gene on chromosome 11, where valine replaces glutamic acid at position 6, producing hemoglobin S (HbS). Under conditions of deoxygenation, acidosis, dehydration, hypothermia, or infection, HbS molecules polymerize into rigid rod-like fibers that distort the normally flexible biconcave erythrocyte into a rigid sickle (crescent) shape. These sickled erythrocytes have several pathological properties: they are rigid and unable to deform through narrow capillaries, they are sticky and adhere to the vascular endothelium via adhesion molecules (VCAM-1, P-selectin,...