Balancing exercise risk and benefits: lessons learned from sickle cell trait and sickle cell anemia

Abstract

Development of exercise guidelines for individuals with sickle cell trait (SCT) and sickle cell anemia (SCA) is hampered by the need to weigh the benefits against risks of exercise in these populations. In SCT, concern for exercise collapse associated with sickle cell trait has resulted in controversial screening of student athletes for SCT. In SCA, there exists unsubstantiated concerns that high-intensity exercise may result in pain and other complications. In both, finding the “right dose” of exercise remains a challenge for patients and their providers. Despite assumptions that factors predisposing to adverse events from high-intensity exercise overlap in SCT and SCA, the issues that frame our understanding of exercise-related harms in both are distinct. This review will compare issues that affect the risk-benefit balance of exercise in SCT and SCA through these key questions: (1) What is the evidence that high-intensity exercise is associated with harm? (2) What are the pathophysiologic mechanisms that could predispose to harm? (3) What are the preventive strategies that may reduce risk? and (4) Why do we need to consider the benefits of exercise in this debate? Addressing these knowledge gaps is essential for developing an evidence-based exercise prescription for these patient populations.

Chronic Disease Management in Sickle Cell Trait Patients in the Primary Care Setting: A Case Report

“…These recommendations were supported by a similar statement from the American Heart Association and American College of Cardiology in 2015 [ 3 , 17 ]. Multiple case reports have identified SCT crises during basic training and other military activities in military recruits and personnel [ 18 ]. However, it is important to still encourage moderate physical fitness in these patients, as blood viscosity and markers of oxidative stress have been found to be lower in trained vs. non-trained SCT patients [ 18 ].…”

High-intensity exercise is a risk factor for renal medullary carcinoma in individuals with sickle cell trait

“…1,2 Additionally, high-intensity exercise among individuals with SCT increases the risk of rhabdomyolysis and sudden cardiac death secondary to tissue hypoxia from RBC sickling. 4,5 To date, however, the renal sequela of exercise in the setting of SCT have not been investigated, and studies of RMC have not identified modifiable risk factors.…”

“…Complications related to hypoxia in the setting of high-intensity exercise have previously been reported among athletes and military recruits with SCT. 4,5 To test whether high-intensity exercise would worsen renal hypoxia among SCT mice, we generated a GEMM of SCT by crossing the hα/hα::β S /β S strain with the Gt(ROSA)26Sor tm2(HIF1A/luc)Kael strain, allowing non-invasive monitoring of HIF1α activity in response to hypoxia using the in vivo imaging system (IVIS) ( Supplementary Fig. 2b ).…”

“…Genotyping conditionsTownes model (hα/hα::β A /β S ): The common (mouse beta KI) forward primer is 5'-TTGAGCAATGTG GACAGAGAAGG; the Beta A reverse primer is 5'-GTTTAGCCAGGGACCGTTTCAG; the Beta S reverse primer is 5'-AATTCTGGCTTATCGGAGGCAAG; the reverse primer for mouse beta wild type is5'-ATGTCAGAAGCAAATGTGAGGAGCA. The separated PCR conditions are as follows: 94°C for 2 minutes, continue PCR for 10 cycles at 94°C for 20 seconds, 65°C with 0.5°C decrease per cycle for 15 seconds, 68°C for 10 seconds, continue PCR for 28 cycles at 94°C for 15 seconds, 60°C for 15 seconds, 72°C for 10 seconds.Cdh16-Cre: The forward primer for the transgene is 5'-GCAGATCTGGCTCTCCAAAG; the forward primer for the internal positive control is 5'-CAAATGTTGCTTGTCTGGTG; the reverse primer for the internal positive control is 5'-GTCAGTCGAGTGCACAGTTT; the reverse primer for the transgene is 5'-AGGCAAATTTTGGTGTACGG.…”

Management of chronic respiratory complications in children and adolescents with sickle cell disease

“…There have been concerns regarding possible adverse effects of high-intensity exercise in patients with SCD as it induces changes that could trigger red blood cell sickling, such as dehydration, moderate temperature changes, lactic acid production, acute inflammation and oxidative stress [83]. However, though evidence is still limited, a regular moderate exercise programme in SCD patients (excluding contact sports, especially in those with splenomegaly) might have several positive effects, including favouring social inclusion and improving overall inflammation and oxidative stress [84].…”