Crises in Sickle Cell Disease

Abstract

In spite of significant strides in the treatment of sickle cell disease (SCD), SCD crises are still responsible for high morbidity and early mortality. While most patients initially seek care in the acute setting for a seemingly uncomplicated pain episode (pain crisis or vaso-occlusive crisis), this initial event is the primary risk factor for potentially life-threatening complications. The pathophysiological basis of these illnesses is end-organ ischemia and infarction combined with the downstream effects of hemolysis that results from red blood cell sickling. These pathological changes can occur acutely and lead to a dramatic clinical presentation, but are frequently superimposed over a milieu of chronic vasculopathy, immune dysregulation, and decreased functional reserve. In the lungs, acute chest syndrome is a particularly ominous lung injury syndrome with a complex pathogenesis and potentially devastating sequelae, but all organ systems can be affected. It is, therefore, critical to understand the SCD patients' susceptibility to acute complications and their risk factors so that they can be recognized promptly and managed effectively. Blood transfusions remain the mainstay of therapy for all severe acute crises. Recommendations and indications for the safest and most efficient implementation of transfusion strategies in the critical care setting are therefore presented and discussed, together with their pitfalls and potential future therapeutic alternatives. In particular, the importance of extended phenotypic red blood cell matching cannot be overemphasized, due to the high prevalence of severe complications from red cell alloimmunization in SCD.

Keywords: acute chest syndrome; red blood cells; sickle cell disease; transfusion.

Figure 1

Causes and mechanisms of acute chest syndrome (ACS). Vaso-occlusive crises precede ACS in 80% of cases and are characterized by red blood cell sickling, cellular hyperadhesion, hemolysis, and vaso-occlusion. These processes are responsible for acute pain and bone marrow necrosis. ACS typically occurs 2.5 days after hospitalization for a vaso-occlusive episode, and radiographically presents as new infiltrates on a chest radiograph. Common causes include fat embolization from necrotic marrow (9% of cases), pulmonary infection (30% of cases), pulmonary infarction (16%), and hypoventilation. In situ pulmonary thrombosis has been identified in 17% of patients with ACS and may also be responsible for infarction. Animal models have shown that by-products of hemolysis, such as heme, cause experimental ACS. As a result of lung injury, ventilation-perfusion mismatches and shunting ensue, with subsequent hemoglobin desaturation and hypoxemia. Tissue hypoxia in turn triggers further sickling in a vicious cycle. The chest radiographs are those of a patient with SCD who received chronic exchange transfusions (note the presence of a double-lumen “port”) on hospital day 1 (top) and day 3 (bottom). By day 3 extensive infiltrates had developed in the patient, who required endotracheal intubation for respiratory failure. PLT = platelet.

Figure 2

CT scan of a patient with acute chest syndrome. A 53-year-old woman with sickle cell disease presented to the emergency department, complaining of pain typical of prior vaso-occlusive pain crises. A CT angiogram obtained on presentation to the emergency department revealed no infiltrate (left); however, extensive bilateral basilar airspace consolidations with small bilateral pleural effusions had developed on a repeat CT angiogram on day 3 (right).