Sudden exertional death in sickle cell trait

In summary, SCT is associated with exertional sudden death. We propose a fundamental role for hyperkalaemia in mediating such deaths. We suggest that local hypoxia and acidosis worsen HbS polymerisation in a vicious (and viscous) circle. Resultant rheological impairment (possibly augmented by local sickling) leads to a sudden decline in skeletal muscle oxygen availability causing metabolic failure. Resultant potassium extrusion is augmented by that resulting directly from RBC deformation. Variation in genes influencing microvascular flow and potassium efflux may modulate the risk of exertional death across a seemingly homogeneous population. We would advocate research in this area. Once initiated, catastrophic decline may prove hard to arrest, meaning that a preventive strategy might best be deployed. While this should certainly include modification of training patterns, it might also be that individuals at risk could be identified through the use of genetic markers in the future. Competing interest None. Provenance and peer review Not commissioned; externally peer reviewed.