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While generally considered benign, sickle cell trait (SCT) is both common and associated with a risk of sudden exertional death. Indeed, all high-level US intercollegiate athletes now face mandatory screening, raising legal and ethical concerns that resonate given the 2012 London Olympics' role in driving universal sports' participation, and increasing public health messaging promoting physical activity. This issue is also of substantial clinical and scientific interest: the pathogenesis of such deaths is unknown and successful management thus impeded.
This article discusses both clinical presentation and relevant (patho)physiology. It also proposes that a vicious cycle of skeletal muscle microvascular occlusion and ‘metabolic failure’ drives potassium efflux from erythrocytes and myocytes and therefore, hyperkalaemic death. Such discussion may be of value to all dealing with subjects with SCT in the community, to emergency/intensive care physicians who treat such cases and to researchers seeking new methods of screening and modes of treatment.
The pathogenesis of exercise-related death among those with SCT is not understood. We hypothesise that potassium efflux from red cells and skeletal muscle causes hyperkalaemic death.
Sickle cell haemoglobin
Each of the haemoglobin (Hb) molecule's four subunits contains an oxygen-carrying haem group and a globin molecule. Two α-subunits are bound to two γ-subunits in fetal haemoglobin (HbF, α2γ2) or two β-subunits in adult haemoglobin (HbA, α2β2). The haemoglobin in which two α-subunits are associated with two mutant β-subunits (in which a hydrophobic valine replaces a hydrophilic glutamic acid) is referred to as sickle cell haemoglobin (HbS).
Hypoxia and falling pH cause HbS to polymerise, distorting red blood cell (RBC) shape (‘sickling’), whose extent depends upon the RBC concentration of HbS relative to HbA/HbF. This is lower in heterozygotes (HbAS with SCT) than homozygotes (HbSS with sickle cell disease (SCD)). Sickling-induced vaso-occlusion can lead to so-called ‘sequestration crises’, but …