Introduction

Hematologic disorders are not often considered in the differential diagnosis of unexpected death in the young, although most physicians would be aware of sudden death as a potential complication of sickle cell anemia. While the mechanism of sudden death in sickle cell disease relates most often to splenic sequestration crisis, other complications may also cause rapid demise. Similarly, the range of lethal mechanisms in other forms of hematologic disorders may be more diverse than initial observations would suggest and includes massive hemorrhage, thromboses, stroke, overwhelming infection, airway obstruction, and cardiac arrhythmia. A list of hematological conditions that may result in sudden death in the young is provided in Table 9.1.

Hemoglobinopathies

Sickle cell anemia

Of all of the disorders caused by structural defects in the hemoglobin molecule, sickle cell disease is the most significant in terms of sudden death. Sickle cell anemia, which results from the replacement of glutamic acid by valine in the sixth position on the β-chain of the hemoglobin molecule, is characterized by decreased plasticity of red blood cells, resulting in elongation and “sickling” (Figure 9.1). The sickled cells are no longer able to traverse normal vascular channels due to their altered configuration, and as such they are more susceptible to damage and more likely to obstruct blood vessels. Sudden death most often results from infection, stroke, splenic sequestration, and pulmonary thromboembolism.