Patient Presentation
A 15-year-old male came to clinic for his health supervision visit and sports physical examination. He had no concerns and he was doing well in school and with his friends. He had a sprained ankle the previous year that he says was well-healed. The past medical history was positive for sickle cell trait.

The pertinent physical exam showed a healthy male with growth parameters in the 50% and normal vital signs. His examination including his musculoskeletal examination was negative.

The diagnosis of a healthy male was made and during the anticipatory examination the physician counseled about the importance of warming up and down during training and the need to stay hydrated. “It’s some of the most important things you can do to be a good athlete. With your sickle cell trait you usually shouldn’t have any problems, but dehydration could cause problems for you. Actually dehydration can cause problems for everyone, so just take an extra ounce or two than everyone else to really stay hydrated,” he counseled.

Discussion
Sickle cell disease (SCD) is a group of inherited blood disorders where there are abnormal hemoglobin molecules and the red blood cells take on a characteristic sickled shape instead of a rounded shape. Sickled hemoglobin provides an evolutionary advantage of giving the individual increased protection against severe and cerebral malaria. The sickled shape doesn’t move through the vascular system as well and therefore is more likely to aggregate in small vessels causing an increased risk of vaso-occlusive disease, acute chest syndrome, splenic sequestration, and priapism. There is also an increased risk of bacteremia. SCD is most common in those individuals with ancestry from the malaria belt or those from Africa, India, Saudi Arabia or the Mediterranean area. It is one of the most common hemoglobin mutations worldwide. There are about 200,000 individuals born with SCD yearly. US prevalence is 70-140,000 patients.

The sickled shape is usually due to a homozygous inheritance, but a heterozygous inheritance causes sickle cell trait (SCT). SCT provides an evolutionary advantage of giving the individual increased protection against severe and cerebral malaria. SCT affects 300 million people globally. In the US 2.5-3 million have SCT and 7-9% of the African-American population has SCT. SCT is generally an asymptomatic carrier state and most people do not have complications. SCT status is important especially for genetic counseling and all US states and many other countries have universal newborn screening for SCD/SCT. Some countries require or offer pre-marital counseling for SCT, where data shows increased knowledge about SCT/SCD but does not change participant reproductive decision making. Potential options for pregnancy planning include preimplantation genetic diagnosis when used with in vitro fertilization, and post-conception includes amniocentesis and chorionic villus sampling.

Learning Point
As stated SCT generally is an asymptomatic carrier state, but people with SCT do have increased risks for various complications. SCT complications are speculated to affect similar organ systems like SCD does. The belief is that low-oxygenic environments in the smallest blood vessels are at risk for sickling and therefore damage and complications, and SCT usually does not sickle but could/can in these environments. Other states which could also affect sickling would be dehydration, acidosis, hypoxia and hyperthermia. High-quality studies in the SCT population are needed to clarify the health-outcomes as many studies are necessarily smaller or not able to be performed as rigorously.

A 2019 systematic review of SCT found that there is a risk for pulmonary embolism, proteinuria and chronic kidney disease (high-strength evidence). There is also a positive association with exertional rhabdomyolysis (moderate-strength evidence). There is no positive association for deep venous thrombosis, cardiomyopathy, heart failure, stroke and no abnormalities of growth parameters in the pediatric population.

Mandated SCT screening for certain individuals such as military recruits and US college athletes is controversial. Some groups and individuals support universal precautions “…(acclimatization, hydration, and optimization of activity duration and recovery)…” for all persons to mitigate exertional-related health problems, which data from US Army supports.

Questions for Further Discussion
1. What is in the differential diagnosis of respiratory distress in a patient with SCD? A review can be found here
2. What are the classifications of genetic disorders and give an example of each? A review can be found here
3. What causes splenomegaly? A review can be found here

Related Cases

Disease: Sickle Cell Trait | Sickle Cell Anemia

Symptom/Presentation: Health Maintenance and Disease Prevention

Specialty: Genetics | Hematology | Orthopaedic Surgery and Sports Medicine

Age: Teenager

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Sickle Cell Disease

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Subramaniam S, Chao JH. Managing Acute Complications Of Sickle Cell Disease In Pediatric Patients. Pediatr Emerg Med Pract. 2016;13(11):1-28.

Pecker LH, Naik RP. The current state of sickle cell trait: implications for reproductive and genetic counseling. Blood. 2018;132(22):2331-2338. doi:10.1182/blood-2018-06-848705

Naik RP, Smith-Whitley K, Hassell KL, et al. Clinical Outcomes Associated With Sickle Cell Trait. Ann Intern Med. 2018;169(9):619-627. doi:10.7326/M18-1161

Wilson S, Ellsworth P, Key NS. Pregnancy in Sickle Trait: What we Know and What we Don’t. Br J Haematol. 2020;190(3):328-335. doi:10.1111/bjh.16518