- Email: [email protected]
Sickle cell trait, exertional rhabdomyolysis, and compartment syndrome
Correspondence
Many of these women conceive naturally and pregnancy can occur any month the tissue is active, which is why gathering robust data requires long-term follow-up for as long as this activity persists. In other words, clinicians and patients should be aware of the complexity of calculating a true pregnancy rate for this procedure, not only in our centre, but also in all programmes worldwide. I declare no competing interests.
Claus Yding Andersen [email protected] Laboratory of Reproductive Biology, University Hospital of Copenhagen, University of Copenhagen, Copenhagen, Denmark 1
2
3
4
5
6
7
Stoop D, Cobo A, Silber S. Fertility preservation for age-related fertility decline. Lancet 2014; 384: 1311–19. Macklon KT, Jensen AK, Loft A, Ernst E, Andersen CY. Treatment history and outcome of 24 deliveries worldwide after autotransplantation of cryopreserved ovarian tissue, including two new Danish deliveries years after autotransplantation. J Assist Reprod Genet 2014; 31: 1557–64. Donnez J, Dolmans M-M, Pellicier A, et al. Fertility preservation for age-related fertility decline. Lancet 2015; 385: 506–07. Greve T, Ernst E, Markholt S, Schmidt KT, Yding Andersen C. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue. Acta Obstet Gynecol Scand 2010; 89: 1589–91. Ernst EH, Offersen BV, Andersen CY, Ernst E. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence. J Assist Reprod Genet 2013; 30: 975–78. Strauss S, Greve T, Ernst E, Fraidakis M, Grudzinskas JG, Andersen CY. Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue. J Assist Reprod Genet 2014; 31: 645–49. Ernst E, Kjærsgaard M, Birkebæk NH, Clausen N, Yding Andersen C. Stimulation of puberty in a girl with chemo—and radiation therapy induced ovarian failure by transplantation of a small part of her frozen/thawed ovarian tissue. Eur J Cancer 2013; 49: 911–14.
Sickle cell trait, exertional rhabdomyolysis, and compartment syndrome I read with interest the Case Report by Ali Ridha and colleagues1 about a US Navy recruit who developed 1948
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.2 The resulting microvascular obstruction would cause muscle ischaemia, leading to rhabdomyolysis.3 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. 3 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,4 and its incidence in the military population has more than tripled between 2006 and 2011.5 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 colleagues5 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 Owen6 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 colleagues1 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.
Philippe Connes [email protected] Laboratory CRIS EA647, Team “Vascular Biology and Red Blood Cell”, University of Lyon, Lyon, France; Institut Universitaire de France, Paris, France 1
2
3
4
5
6
Ridha A, Khan A, Al-Abayechi S, Puthenveetil V. Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patient. Lancet 2014; 384: 2172. O’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: 2045–56. Tripette J, Hardy-Dessources MD, Romana M, et al. Exercise-related complications in sickle cell trait. Clin Hemorheol Microcirc 2013; 55: 29–37. Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician 2002; 65: 907–12. Deuster PA, Contreras-Sesvold CL, O’Connor FG, et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol 2013; 113: 1997–2004. Kimmick G, Owen J. Rhabdomyolysis and hemolysis associated with sickle cell trait and glucose-6-phosphate dehydrogenase deficiency. South Med J 1996; 89: 1097–98.
www.thelancet.com Vol 385 May 16, 2015
Many of these women conceive naturally and pregnancy can occur any month the tissue is active, which is why gathering robust data requires long-term follow-up for as long as this activity persists. In other words, clinicians and patients should be aware of the complexity of calculating a true pregnancy rate for this procedure, not only in our centre, but also in all programmes worldwide. I declare no competing interests.
Claus Yding Andersen [email protected] Laboratory of Reproductive Biology, University Hospital of Copenhagen, University of Copenhagen, Copenhagen, Denmark 1
2
3
4
5
6
7
Stoop D, Cobo A, Silber S. Fertility preservation for age-related fertility decline. Lancet 2014; 384: 1311–19. Macklon KT, Jensen AK, Loft A, Ernst E, Andersen CY. Treatment history and outcome of 24 deliveries worldwide after autotransplantation of cryopreserved ovarian tissue, including two new Danish deliveries years after autotransplantation. J Assist Reprod Genet 2014; 31: 1557–64. Donnez J, Dolmans M-M, Pellicier A, et al. Fertility preservation for age-related fertility decline. Lancet 2015; 385: 506–07. Greve T, Ernst E, Markholt S, Schmidt KT, Yding Andersen C. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue. Acta Obstet Gynecol Scand 2010; 89: 1589–91. Ernst EH, Offersen BV, Andersen CY, Ernst E. Legal termination of a pregnancy resulting from transplanted cryopreserved ovarian tissue due to cancer recurrence. J Assist Reprod Genet 2013; 30: 975–78. Strauss S, Greve T, Ernst E, Fraidakis M, Grudzinskas JG, Andersen CY. Administration of DHEA augments progesterone production in a woman with low ovarian reserve being transplanted with cryopreserved ovarian tissue. J Assist Reprod Genet 2014; 31: 645–49. Ernst E, Kjærsgaard M, Birkebæk NH, Clausen N, Yding Andersen C. Stimulation of puberty in a girl with chemo—and radiation therapy induced ovarian failure by transplantation of a small part of her frozen/thawed ovarian tissue. Eur J Cancer 2013; 49: 911–14.
Sickle cell trait, exertional rhabdomyolysis, and compartment syndrome I read with interest the Case Report by Ali Ridha and colleagues1 about a US Navy recruit who developed 1948
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.2 The resulting microvascular obstruction would cause muscle ischaemia, leading to rhabdomyolysis.3 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. 3 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,4 and its incidence in the military population has more than tripled between 2006 and 2011.5 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 colleagues5 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 Owen6 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 colleagues1 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.
Philippe Connes [email protected] Laboratory CRIS EA647, Team “Vascular Biology and Red Blood Cell”, University of Lyon, Lyon, France; Institut Universitaire de France, Paris, France 1
2
3
4
5
6
Ridha A, Khan A, Al-Abayechi S, Puthenveetil V. Acute compartment syndrome secondary to rhabdomyolysis in a sickle cell trait patient. Lancet 2014; 384: 2172. O’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: 2045–56. Tripette J, Hardy-Dessources MD, Romana M, et al. Exercise-related complications in sickle cell trait. Clin Hemorheol Microcirc 2013; 55: 29–37. Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician 2002; 65: 907–12. Deuster PA, Contreras-Sesvold CL, O’Connor FG, et al. Genetic polymorphisms associated with exertional rhabdomyolysis. Eur J Appl Physiol 2013; 113: 1997–2004. Kimmick G, Owen J. Rhabdomyolysis and hemolysis associated with sickle cell trait and glucose-6-phosphate dehydrogenase deficiency. South Med J 1996; 89: 1097–98.
www.thelancet.com Vol 385 May 16, 2015