This chapter addresses clinical presentations of sickle cell disease that are uncommon or newly emerging or that pose special diagnostic and therapeutic challenges. Many of them are life threatening or can result in severe loss of organ function. Some clinical presentations also illustrate features of sickle cell disease pathophysiology that are not always recognized in the more common complications such as pain crisis and chest syndrome. There are no clinical trials and few published reviews dealing with these issues, their pathogenetic mechanisms, or their treatment. Hence, the diagnostic and management measures suggested here necessarily are based on published single reports and small case series and on clinical experience. Acute multiorgan failure syndrome is summarized first because of its life-threatening potential and also because its clinical features and treatment are similar to some of the other, less common conditions discussed. Information on drug-induced pain episodes (crises) is included primarily to promote awareness of these newly emerging and unexpected complications. The chapter ends with descriptions of how other, nonsickling, red cell disorders affect patients with sickle cell disease, with a special emphasis on the immune hemolysis that characterizes sickle-related hyperhemolysis syndrome.
Acute Multiorgan Failure Syndrome
Definition, Epidemiology, and Putative Pathophysiology
Acute multiorgan failure (MOF) syndrome refers to the acute onset of the failure of at least 2 of 3 vital organ systems in the setting of an acute sickle cell vaso-occlusive episode (VOE). As defined by the initial case series,1 the syndrome occurs in the absence of sepsis or other comorbidities that might lead to MOF in a patient without sickle cell disease. Furthermore, the syndrome may account for up to 10% of deaths in sickle cell patients.2 The specific mechanisms whereby acute simultaneous severe injury occurs in the lungs, liver, and/or kidneys have not been defined but may reflect an acute cytokine-mediated systemic inflammatory response that is associated with several subsequent processes including activation of endothelium with diffuse worsening vaso-occlusion and hemolysis. Case reports also document evidence of fat emboli, thought to arise from severe bone marrow necrosis (see later discussion), and the occurrence of MOF in patients with relatively high baseline hemoglobin values and in patients with all types of sickle cell disease including HbSC disease and HbS-β+ thalassemia.3
Clinical Presentation and Diagnosis
MOF most often arises in hospitalized patients 2 to 3 days after presentation for a VOE that is described as more severe or diffuse than is typical for an individual.1 This complication arises in up to 90% of adults with rapidly progressive acute chest syndrome as manifested by the development of acute severe respiratory failure in <24 hours.4 Fever and tachycardia are common early signs. The development of somnolence and mental status changes may reflect hypoxia and the effects of acute hepatic and renal failure. Clinical manifestations include acute worsening of ...