Comment on: negative health implications of sickle cell trait in high income countries: from the football field to the laboratory.

Abstract

I read with interest the review by Key et al (2015) that addressed important aspects of individuals with sickle cell trait (SCT) and certain features of their red blood cells. I wish to add a few more aspects of SCT that may complement that review (Key et al, 2015). These are listed and discussed below. Although Key et al (2015) alluded to other genetic factors that influence skeletal muscle activity, they did not elaborate on the types and function of skeletal muscle fibres in African Americans versus Caucasians. Basically, skeletal muscle fibres fall into two major functional types: slow switch fibres (Type 1), characterized by aerobic metabolism for sustained function, and fast switch fibres (Types 2A, 2B, and 2D/X), characterized by anaerobic metabolism for intermittent activity (Schiaffino & Reggiani, 2011). Moreover, Type 1 fibres are predominant in heart and neck muscles whereas Type 2 fibres are abundant in trunk and limb muscles. Another study found that Type 2A fibres and the activities of the muscle enzymes of the anaerobic metabolic pathway were significantly higher in African American males than in Caucasian males (Ama et al, 1986). Together, these findings suggest that sustained activity in the African American athlete with SCT would be associated with enhanced anaerobic metabolism culminating in rhabdomyolysis in some individuals whereas intermittent activity would abort the potential side effects. As mentioned by Key et al (2015), haemolysis and oxidative stress are important factors in the generation of vasculopathy, both in acute vaso-occlusive events and in chronic organ damage. However, the relative contributions of polymerization versus oxidative damage that directly cause haemolysis are complicated by the fact that sickle cells drawn from a patient with sickle cell anaemia (SCA) have already been affected by multiple rounds of sickling/unsickling and oxidative damage in vivo before they are collected. Presley et al (2010) reasoned that determination of the mechanical fragility of SCT red blood cells (RBCs) that do not sickle in vivo but can be made to do so in vitro would explain the relative pathophysiological importance of haemolysis versus oxidative damage. They explored this by determining the effects of a single sickling event on the mechanical fragility of SCT RBCs that have never sickled before. They found that the mechanical fragility of SCT RBCs increased dramatically after a single sickling event, suggesting that a substantial amount of in vivo haemolysis occurs in polymer-containing cells and that it is likely that many cells that haemolyse in vivo do so on the first sickling event (Presley et al, 2010). People with SCT can donate blood, just like any other donor, provided they meet the blood bank criteria for donation. Nevertheless, there are certain precautions necessary for the processing and release of SCT blood in certain situations, as listed in Table 1. Noteworthy among these is that SCT blood blocks white blood cell filters; improving oxygen tension may improve filtration (Gorlin & Gudino, 2001; Byrne et al, 2003). Moreover, administration of granulocyte colony-stimulating factor to trait individuals to increase the number of peripheral stem cells is contraindicated because it could be fatal (Abboud et al, 1998). Primary prevention of SCA and related sickle cell syndromes is best achieved by prenatal diagnosis. Pregnant women whose fetuses are at risk for SCA or other sickle cell syndromes should be identified and counselled. A thorough personal history, family history and physical examination, with complete blood count and Hb electrophoresis should be performed. If the haemoglobin (Hb) electrophoresis is normal, no further work-up is needed, but if it shows that the woman is a carrier of the sickle gene or the gene of another abnormal Hb, a similar evaluation must be performed on the father of the fetus. If the father's Hb electrophoresis is normal, no further work-up is needed, but the couple should be informed that there is a 25% chance for the fetus of each pregnancy to be a carrier of the same abnormal Hb as the mother. If the father's Hb electrophoresis also shows the presence of sickle Hb or another abnormal Hb, the fetus is at risk for SCA or another sickle cell syndrome. At this point, thorough family and genetic counselling must be conducted in preparation for possible prenatal diagnosis. The couple must fully understand the prenatal diagnosis procedure including the methods used, possible outcomes and possible complications (Ballas, 2014). None declared.