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Sickle cell trait — Clinical Guidelines

Overview

Sickle cell trait (SCT) results from heterozygosity for the β-globin sickle cell mutation, typically benign but associated with increased risks under extreme conditions such as severe dehydration, intense physical activity, and certain medical procedures. 1

Diagnosis

Genetic Testing: Hemoglobin electrophoresis to identify the presence of hemoglobin S (HbS). 1 12 25

Blood Films: May show occasional sickled cells, though findings can be inconsistent. 25

Methylation Profiling: Emerging evidence suggests potential role in understanding SCT impacts through DNA methylation patterns. 1

Management

Hydration and Acclimatization: Essential for athletes and individuals undergoing high-risk procedures to prevent sickling crises. 20 3

Medical Counseling: Detailed pre-procedure and pre-exercise counseling focusing on risk mitigation strategies. 20

Avoid Hypoxic Conditions: Minimize exposure to low oxygen environments, particularly during surgeries or intense physical activities. 3 20

Special Populations

Pregnancy: Maternal SCT does not significantly impact neonatal birth weight or size in most studies, though some variability exists. 34 37

Athletes: Screening mandated by organizations like NCAA; careful monitoring and management strategies are crucial due to increased risk of exertional sickling. 4 10 14

Comorbidities: Rare cases report SCT association with thromboembolic events, gout, and unusual complications like splenic infarction without hypoxia. 29 7 50

Key Recommendations

Screen Athletes for SCT: Implement mandatory screening for SCT in collegiate and competitive athletes to identify and manage risks effectively. (Evidence: Moderate) 4 10 14

Counsel on Hydration and Acclimatization: Provide comprehensive counseling to individuals with SCT, especially athletes and those undergoing high-risk procedures, emphasizing hydration and acclimatization to prevent sickling crises. (Evidence: Moderate) 20 3

Monitor and Manage High-Risk Situations: Exercise caution and implement specific management protocols during surgeries and intense physical activities for individuals with SCT to mitigate risks. (Evidence: Moderate) 3 20

References

1 Vasconcelos AG, Johnson M, Cai Y, Hsu L, Franceschini N, Auer PL et al.. Methylation profile of individuals with sickle cell trait. Epigenetics 2025. link 2 Brechko A, Abdullahi SU, Gambo S, Murtala HA, Kabir H, Shamsu KA et al.. Adherence to ready-to-use therapeutic food in older children with sickle cell anaemia and severe acute malnutrition: a mixed-methods study in a low-income setting. BMJ global health 2025. link 3 Ali JM, Besser M, Goddard M, Abu-Omar Y, Catarino P, Bhagra S et al.. Catastrophic sickling crisis in patient undergoing cardiac transplantation with sickle cell trait. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 2019. link 4 McDonald MA, Creary MS, Powell J, Daley LA, Baker C, Royal CD. Perspectives and Practices of Athletic Trainers and Team Physicians Implementing the 2010 NCAA Sickle Cell Trait Screening Policy. Journal of genetic counseling 2017. link 5 Shephard RJ. Sickle cell trait: what are the costs and benefits of screening?. The Journal of sports medicine and physical fitness 2016. link 6 Ferrari R, Parker LS, Grubs RE, Krishnamurti L. Sickle Cell Trait Screening of Collegiate Athletes: Ethical Reasons for Program Reform. Journal of genetic counseling 2015. link 7 Umesh S, Ajit NE, Shobha V, Nazuralla S, Ross C, Choudhury R. Musculoskeletal disorders in sickle cell anaemia--unusual associations. The Journal of the Association of Physicians of India 2014. link 8 Khozaim K, Schellinger M, Cummings O, Robinson B. Peripartum acute liver failure from a vaso-occlusive crisis in a patient with sickle cell trait. Journal of perinatology : official journal of the California Perinatal Association 2013. link 9 Thompson AA. Sickle cell trait testing and athletic participation: a solution in search of a problem?. Hematology. American Society of Hematology. Education Program 2013. link 10 Harmon KG, Drezner JA, Klossner D, Asif IM. Sickle cell trait associated with a RR of death of 37 times in National Collegiate Athletic Association football athletes: a database with 2 million athlete-years as the denominator. British journal of sports medicine 2012. link 11 Shackelford SD, King DA, Wheeler TL. Chilling rate effects on pork loin tenderness in commercial processing plants. Journal of animal science 2012. link 12 Aloe A, Krishnamurti L, Kladny B. Testing of collegiate athletes for sickle cell trait: what we, as genetic counselors should know. Journal of genetic counseling 2011. link 13 Acharya K, Benjamin HJ, Clayton EW, Ross LF. Attitudes and beliefs of sports medicine providers to sickle cell trait screening of student athletes. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine 2011. link 14 Jung AP, Selmon PB, Lett JL, Petrella JK. Survey of sickle cell trait screening in NCAA and NAIA institutions. The Physician and sportsmedicine 2011. link 15 Connes P. Hemorheology and exercise: effects of warm environments and potential consequences for sickle cell trait carriers. Scandinavian journal of medicine & science in sports 2010. link 16 Anionwu EN. 'In those days it was rare for a nurse to be actively involved in a study of this kind'. Nurse researcher 2007. link 17 Eichner ER. Sickle cell trait. Journal of sport rehabilitation 2007. link 18 Hooper CY, Fraser-Bell S, Farinelli A, Grigg JR. Complicated hyphaema: think sickle. Clinical & experimental ophthalmology 2006. link 19 Mohapatra MK. Type 1 diabetes mellitus in homozygous sickle cell anaemia. The Journal of the Association of Physicians of India 2005. link 20 Small E. Sickle cell trait and sudden death. Pediatric annals 2003. link 21 Ballas SK. Sickle cell anaemia: progress in pathogenesis and treatment. Drugs 2002. link 22 Budhoo MR, Mitchell S, Eddlestone J, MacLennan I. Sickle cell trait and acute intermittent porphyria leading to small bowel infarction. Journal of the Royal College of Surgeons of Edinburgh 1999. link 23 Macdonald A. An unusual cause of haematuria. The New Zealand medical journal 1999. link 24 Coogan CL, McKiel CF, Flanagan MJ, Bormes TP, Matkov TG. Renal medullary carcinoma in patients with sickle cell trait. Urology 1998. link00104-6) 25 Pepple DJ. Sickle cell trait: dual picture of blood films. Medical hypotheses 1995. link90129-9) 26 Leavitt JA, Butrus SI. Internuclear ophthalmoplegia in sickle cell trait. Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society 1994. link 27 Multon O, Sibony O, Carbillon L, Guerin JM, Nessman C, Blot P. Sickle cell and thiamine deficiency: case report of a fetal death. Fetal diagnosis and therapy 1994. link 28 Lama M. Hepatic abscess in sickle cell anaemia: a rare manifestation. Archives of disease in childhood 1993. link 29 Humphries JE, Wheby MS. Case report: sickle cell trait and recurrent deep venous thrombosis. The American journal of the medical sciences 1992. link 30 Pepple DJ. On the protective mechanism of the sickle cell trait (HbAS). Medical hypotheses 1992. link90124-u) 31 Thiriet P, Lobe MM, Gweha I, Gozal D. Prevalence of the sickle cell trait in an athletic West African population. Medicine and science in sports and exercise 1991. link 32 Le Gallais D, Préfaut C, Dulat C, Macabies J, Lonsdorfer J. Sickle cell trait in Ivory Coast athletic champions, 1956-1989. International journal of sports medicine 1991. link 33 Saad ST, Arruda VR, Junqueira OO, Schelini FA, Coelho OB. Acute myocardial infarction in sickle cell anaemia associated with severe hypoxia. Postgraduate medical journal 1990. link 34 Okonofua FE, Odutayo R, Onwudiegwu U. Maternal sickle cell trait is not a cause of low birthweight in Nigerian neonates. International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics 1990. link90110-7) 35 Lee MG. Abdominal pain in sickle cell anaemia. Tropical doctor 1989. link 36 McGovern E, Otridge BW, Neligan MC. Mitral valve replacement in a patient with sickle cell anaemia. The Thoracic and cardiovascular surgeon 1987. link 37 Roopnarinesingh S, Ramsewak S. Decreased birth weight and femur length in fetuses of patients with the sickle-cell trait. Obstetrics and gynecology 1986. link 38 Willcox MC, Liljestrand J, Bergström S. Abnormal haemoglobins among pregnant women from Mozambique. Journal of medical genetics 1986. link 39 das Graças de Freitas Sousa M, Azevêdo ES. Multivariate study of birth weight and maternal heterozygosity for sickle cell anemia in Bahia, Brazil. Human heredity 1984. link 40 Nussbaum RL, Rice L. Morbidity of sickle cell trait at high altitude. Southern medical journal 1984. link 41 Adeyokunnu AA. Bilateral gangrene of the feet associated with Salmonella infection in children with sickle cell anaemia. Annals of tropical paediatrics 1982. link 42 Jeyakumar LH, French MR. Polymorphic acetylation of sulphamethazine in man: acetylator phenotype in sicklers and non-sicklers. Toxicology letters 1980. link90130-7) 43 Rayman RB. Sickle cell trait and the aviator. Aviation, space, and environmental medicine 1979. link 44 Facer CA, Brown J. Incidence of abnormal haemoglobin traits among Gambian children. Transactions of the Royal Society of Tropical Medicine and Hygiene 1979. link90090-7) 45 Richie JP, Kerr WS. Sickle cell trait: forgotten cause of hematuria in white patients. The Journal of urology 1979. link56287-4) 46 Ashcroft MT, Desai P, Grell GA, Serjeant BE, Serjeant GR. Heights and weights of West Indian children with the sickle cell trait. Archives of disease in childhood 1978. link 47 Nhonoli AM, Kujwalile JM, Kigoni EP, Masawe AE. Correlation of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency and sickle cell trait (Hb-AS). Tropical and geographical medicine 1978. link 48 Bloomfield RD, Suarez JR, Malangit AC. The placenta: a diagnostic tool in sickle cell disorders. Journal of the National Medical Association 1978. link 49 Crane DB, Hackler RH, Fischer LM. Significant hematuria secondary to sickle cell trait in a white family. Southern medical journal 1977. link 50 King DT, Lindstrom RR, State D, Hirose FM, Schwartz A. Unusual cause of acute abdomen. Sickle cell trait and nonhypoxic splenic infarction. JAMA 1977. link 51 Finelli PF. Sickle cell trait and transient monocular blindness. American journal of ophthalmology 1976. link90370-6) 52 Nance WE, Grove J. Genetic determination of phenotypic variation in sickle cell trait. Science (New York, N.Y.) 1972. link

Sickle cell trait