Sickle cell trait, exertional rhabdomyolysis, and compartment syndrome

Abstract

I read with interest the Case Report by Ali Ridha and colleagues1Ridha A Khan A Al-Abayechi S Puthenveetil V Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patient.Lancet. 2014; 384: 2172Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar about a US Navy recruit who developed exertional rhabdomyolysis. The authors proposed that the patient's sickle cell trait might have precipitated the occurrence and the worsening of this complication. Metabolic changes occurring during exercise were suggested to promote the polymerisation of haemoglobin S and red blood cell sickling.2O'Connor FG Bergeron MF Cantrell J et al.ACSM and CHAMP summit on sickle cell trait: mitigating risks for warfighters and athletes.Med Sci Sports Exerc. 2012; 44: 2045-2056Crossref PubMed Scopus (56) Google Scholar The resulting microvascular obstruction would cause muscle ischaemia, leading to rhabdomyolysis.3Tripette J Hardy-Dessources MD Romana M et al.Exercise-related complications in sickle cell trait.Clin Hemorheol Microcirc. 2013; 55: 29-37PubMed Google Scholar Unfortunately, oxygen therapy did not improve the condition of the patient, who developed compartment syndrome. However, whether red blood cell sickling is truly the cause of this complication is unknown. The presence of sickled red blood cells has rarely been observed in peripheral blood from exercising sickle cell trait carriers.3Tripette J Hardy-Dessources MD Romana M et al.Exercise-related complications in sickle cell trait.Clin Hemorheol Microcirc. 2013; 55: 29-37PubMed Google Scholar Moreover, muscle biopsies in this population show the presence of wider capillaries than in individuals without sickle cell trait, suggesting that a small loss of red blood cell deformability caused by the polymerisation of less than 40–45% of haemoglobin S could not be sufficient to occlude these large capillaries. Exertional rhabdomyolysis affects one in 10 000 people per year,4Sauret JM Marinides G Wang GK Rhabdomyolysis.Am Fam Physician. 2002; 65: 907-912PubMed Google Scholar and its incidence in the military population has more than tripled between 2006 and 2011.5Deuster PA Contreras-Sesvold CL O'Connor FG et al.Genetic polymorphisms associated with exertional rhabdomyolysis.Eur J Appl Physiol. 2013; 113: 1997-2004Crossref PubMed Scopus (39) Google Scholar Whereas sickle cell trait could increase the risks of exertional rhabdomyolysis in people of African descent, other inherited metabolic muscle disorders could be involved too. Patricia Deuster and colleagues5Deuster PA Contreras-Sesvold CL O'Connor FG et al.Genetic polymorphisms associated with exertional rhabdomyolysis.Eur J Appl Physiol. 2013; 113: 1997-2004Crossref PubMed Scopus (39) Google Scholar reported that the GG genotype of the muscle-specific creatine kinase isoform (CKMM) Nco1 polymorphism was associated with an increased risk for exertional rhabdomyolysis and was more frequently found in African Americans (28·1%) than in white people (14·2%). They also reported that individuals with the myosin light chain kinase 2 (MYLK2) A allele—an allele also more frequently encountered in African Americans than in white people—were more likely to have had a clinical episode of exertional rhabdomyolysis. Moreover, the presence of another genetic defect could also transform the silent sickle cell trait into a syndrome resembling sickle cell disease with vaso-occlusion. For instance, Gretchen Kimmick and John Owen6Kimmick G Owen J Rhabdomyolysis and hemolysis associated with sickle cell trait and glucose-6-phosphate dehydrogenase deficiency.South Med J. 1996; 89: 1097-1098Crossref PubMed Scopus (13) Google Scholar described the case of a black man with both sickle cell trait and glucose-6-phosphate dehydrogenase (G6PD) deficiency who developed exertional rhabdomyolysis at different occasions. Since G6PD deficiency and sickle cell trait can be expected to occur simultaneously in up to 1% of men of African descent, physicians should be encouraged to screen for the former defect too. Indeed, an alternative hypothesis to that proposed by Ridha and colleagues1Ridha A Khan A Al-Abayechi S Puthenveetil V Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patient.Lancet. 2014; 384: 2172Summary Full Text Full Text PDF PubMed Scopus (9) Google Scholar is that haemoglobin S could be a surrogate for or act in combination with other gene variants to precipitate severe exertional rhabdomyolysis. Screening for other genetic variants might help to clarify the pathophysiological mechanisms underlying exertional rhabdomyolysis in people of African ethnic origin. I declare no competing interests. Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patientA 30 year-old African American man presented to the emergency department in North Chicago, Illinois, in May, 2014, complaining of 1 day of severe left leg pain, exacerbated by moving the leg. He had a history of sickle cell trait which had been diagnosed when he joined the US Navy and was doing boot camp as part of his basic naval training. After 3 weeks at boot camp the patient complained of constant sharp pain in his left shin, 10/10 in severity, that started suddenly while he was running the first lap of his daily exercise, and became so severe that he was unable to weight bear. Full-Text PDF