Sporting Activities Management of the Sickle Cell Trait: History
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Subjects: Health Care Sciences & Services
Contributor:
Valeria Maria Pinto
,
Lucia De Franceschi
,
Barbara Gianesin
,
Antonia Gigante
,
Giovanna Graziadei
,
Letizia Lombardini
,
Giovanni Palazzi
,
Alessandra Quota
,
Rodolfo Russo
,
Laura Sainati
,
Donatella Venturelli
,
Gian Luca Forni
,
Raffaella Origa

The number of individuals with the sickle cell trait exceeds 300 million worldwide, making sickle cell disease one of the most common monogenetic diseases globally. Because of the high frequency of sickle cell disease, reproductive counseling is of crucial importance. In addition, unlike other carrier states, Sickle Cell Trait (SCT) seems to be a risk factor for several clinical complications, such as extreme exertional injury, chronic kidney disease, and complications during pregnancy and surgery.

  • sickle cell trait
  • hemoglobinopathies
  • sporting activities

1. Introduction

The sickle cell trait is the carrier state for the sickle hemoglobin (HbS) mutation. HbS is the result of a point mutation on a single nucleotide base of the gene encoding the beta (β) subunit of hemoglobin chains. As a result of this mutation, an adenine replaces a thymine, causing the replacement of one amino acid (glutamic acid) with another (valine) [1]. In conditions of low oxygen tension, abnormal HbS polymerizes and erythrocytes stretch and bend, assuming the characteristic sickle shape; they can build up, producing obstructions to circulation that, especially in its homozygous form (drepanocytosis, sickle cell anemia or sickle cell disease (SCD)), can cause painful health emergencies, such as vaso-occlusive crises and other possibly serious consequences. It affects both quality of life and life expectancy [2][3][4][5][6].
The sickle cell trait (SCT) condition is frequently found in patients of African origin or in those who come from regions where malaria is endemic (such as tropical and subtropical regions). Approximately 300 million people are thought to be affected by SCT worldwide, approximately one-third of whom live in subSaharan Africa [7][8][9][10]. The prevalence of SCT in some of these areas is over 25% and can even reach 45% (Nigeria [11]). As a result of the slave trade and, more recently, of migration flows, the HbS gene has spread in America, Europe, and Australia. The prevalence of SCT in the United States of America affects 7–9% of the African American population (equal to approximately 3 million people) and 0.2% of the Caucasian population. In Italy, HbS was, historically, almost exclusively present in southern regions, especially in Sicily, where SCT prevalence reaches peaks of 13% in some areas. However, as a result of the south–north migration flows and of more recent international migration flows (from, for example, Africa and Albania), SCT is now present throughout the Italian national territory [12][13].
The association between malaria and SCT was reported for the first time by Allison in 1954 [14]. Although patients affected by SCT are not protected from parasitemia when exposed to Plasmodium falciparum, they are nevertheless unlikely to develop severe consequences from malarial infection, with a reduction of approximately 90% in the infection’s clinical impact [15].
HbS concentration can vary considerably from 25 to 45%; it generally stands at approximately 40%. In the African American population, the co-presence of a deletion of the alpha-globin gene (−α/αα, present in 30% of the population) or of two alpha-globin genes (−α/−α, present in 2% of the population) can cause a variation in HbS equal to approx. 37% and 29%, respectively [16].
A person with SCT status usually has a normal life expectancy and quality of life [8]. However, very rarely and under certain metabolic or environmental conditions, such as hypoxia, acidosis, dehydration, hyperosmolarity, and hyperthermia, some complications of the sickle cell disease can occur. Therefore, specific precautions must be taken to avoid possible dehydration conditions in the event of prolonged exposure to heat, heatstroke, or low oxygen tension, as could occur in high mountains or severe physical stresses, such as those experienced in certain types of sports activities and during major surgeries.
Moreover, the association between SCT and red blood cell disease due to the presence of membrane or enzymatic defects (spherocytosis and stomatocytosis) could exacerbate the phenotypic expression of SCT. Therefore, especially in “symptomatic” cases of SCT, the coexistence of possible red blood cell membrane or enzymatic defects should be investigated.
Hence, although SCT is largely considered to be a benign condition, it may in fact be a risk factor for some clinical symptoms.
The major clinical complications of SCT and proposed counseling recommendations are summarized in Table 1.
Table 1. Major clinical complications of sickle cell trait and proposed counseling recommendations.
Complication Counseling Recommendations
Renal medullary carcinoma In the event of micro- or macroscopic hematuria,
prompt referral to renal imaging (echo or abdominal contrast CT scan)
Chronic kidney disease Early identification of kidney damage through an annual check of serum creatinine levels, chemical urinalysis, and periodic blood pressure measurement
Stroke No evidence of increased risk of early-onset stroke with SCT; additional work-up to identify causes; 30-day mortality worse than without SCT
Venous thromboembolism SCT is a weak risk factor; decisions regarding choice and duration of anticoagulation should not be influenced by the presence of SCT
Venous thromboembolism during pregnancy Collecting history regarding prior thromboembolic events and/or miscarriages; close monitoring for thromboembolic events
Hypertension during pregnancy Close monitoring for blood pressure and proteinuria
Urinary infection during pregnancy Serial testing for chemical urinalysis and urine culture, early antibiotic treatment in case of infection or suspected pyelonephritis
Hyphema, eye trauma, and eye surgery Monitoring for increased risk of ischemic complications; consider prophylactic transfusional therapy before surgery (simple transfusion or erythrocytapheresis)
High-risk surgery (cardiac surgery, intrathoracic surgery, brain surgery, transplant surgery, major vascular surgery, major spine surgery, surgeries requiring prolonged general anesthesia for >4 h) Consider prophylactic transfusional therapy within a week of the scheduled surgery: erythrocytapheresis (automated red cell exchange or manual exchange) to bring HbS values to percentages of <30%, or simple transfusion in the case of anemia
CT: computed tomography; SCT: sickle cell trait.

2. SCT and Sporting Activities

All preventive measures described here in relation to the possible effects of intense physical exertion should be taken by all athletes in order to safeguard their health.

2.1. Is There an Increased Risk of Exercise-Related Morbidity and/or Mortality in the SCT Population?

Exercise-related morbidity and mortality in individuals affected by SCT are mainly linked to a very rare clinical issue referred to as exertional rhabdomyolysis and to exercise-related sudden death, which can occur under extreme conditions, such as severe dehydration and high-intensity physical activity.
Studies report that severe or fatal exertional rhabdomyolysis is attributable to a wide range of activities (football, training, cross-country racing, swimming, spinning, hockey, exercises in the army, etc.) in which the effort undergone by the individual can be classified as intense. The same studies also describe compartment syndromes, hematuria and isosthenuria [17][18].
During intense physical exertion, exertional rhabdomyolysis manifests as extreme muscle weakness and pain, even mild pain, which arises rapidly without prodromes. Rhabdomyolysis can be fulminant with muscle cell death, potassium release, hypercalcemia, and the death of the subject due to the fact of arrythmia [19][20].
Documented sports activities, the clinical picture and evolution, the causes of exertional sickling, and inducing and protective factors are summarized in Table 2.
Table 2. Exertional collapse associated with sickle cell trait.
Documented Sports Activities Clinical Picture Evolution
Football, training, cross-country racing, swimming, spinning, hockey, military exercises Extreme muscle weakness, pain, even mild, with rapid onset without prodromes Initially conscious subject,
Loss of consciousness, Mental confusion, Tachycardia, arrhythmia, Death
Causes of Exertional Sickling Inducing Factors Genetic Factors
Extreme physical effort for as little as a few minutes (2–5), even in trained subjects/professional athletes Prolonged intense exercise, dehydration, high temperatures, altitude, suboptimal physical conditions, fever; intake of the following drugs: antipsychotics, antihistamines, decongestants, statins; intake of caffeine-stimulant drinks Protective: high levels of fetal Hb (HbF); coexistence of alpha-thalassemia
Aggravating; high amount (%) of HbS; coexistence of red blood cell membrane or enzymatic defect
Several studies conducted in a military environment and, above all in, football [21] report that sudden death is the most dangerous complication in individuals, athletes, and soldiers with SCT [22][23]. The risk of sudden death in recruits with SCT during intense exertion (assessed in 2 million military recruits in the USA) is estimated to be 30 times higher among African American individuals and 40 times higher than that in recruits in general [24]. Death is mainly attributed to exertional rhabdomyolysis during the first month of training and during activities requiring high-intensity exercises [25]. The increase in deaths correlates with age (higher at 28–29 years than at 17–18 years), probably due to the cumulative effect of renal papillary necrosis and the resulting isosthenuria, which is common in SCT (it is observed in 85% of individuals of the age of male recruits [24]). In more recent studies, HbAS was associated with a higher adjusted risk of exertional rhabdomyolysis for military men (hazard ratio: 1.54; 95% CI 1.12 to 2.12; p = 0.008). The risk was 57% higher in men >36 years old [26].

2.2. What Precautions Should Be Taken?

If preventive measures are taken, the risk of sudden death attributed to SCT seems to be zeroed [26].
Hydration and training with progressive exercises can “revert”/normalize some hematological abnormalities (increased plasma viscosity, oxidative stress, endothelial activation, and sickling) observed during exertion [21].
Coaches, athletic trainers, and medical staff should follow universal training precautions [27]. Coaches must be aware of the potential dangers during training; therefore, they should avoid repetitive and intense activities without breaks and stop the exercises immediately and alert the doctor if an athlete shows signs of exertional rhabdomyolysis.
It is essential to prepare an emergency management plan in advance, as well as ensuring that the necessary equipment is available during all training sessions and competitions.

2.3. Can Individuals with SCT Practice Sports Activities and Undertake Them at a Competitive Level?

The benefits of (aerobic and anaerobic) physical activity in SCT carriers are similar to those experienced by individuals without SCT; therefore, SCT carriers should be encouraged to practice sports.
However, sports clubs and coaches must implement strategies to reduce any risks associated with the player’s SCT status; these include appropriate training and monitoring during training.
If the athlete is aware of his/her SCT status, appropriate precautions should be taken regarding individualized training methods and resting periods.
If the SCT status is not known, preventive measures should be adopted anyway to safeguard all athletes.
It is important that coaches and physical trainers are aware of the possible presence of SCT carriers among their athletes and that training sessions in general include appropriate rest intervals and hydration. In addition to this, coaches and trainers should be able to recognize the early signs of specific symptoms that may arise during physical exertion in athletes with SCT and to initiate early treatment.
No contraindications to sports activities are reported for athletes with SCT.

2.4. Can Individuals with SCT Practice High-Altitude (e.g., Mountain Climbing) or High-Pressure (e.g., Scuba Diving) Activities?

(A)
 High-altitude activities
Only individual cases are reported in the literature; there are no studies with large numbers of splenic infarctions secondary to high-altitude flights in unpressurized aircraft or during mountaineering excursions. Usually, the altitude at which athletes can train or compete is between 2000 and 2500 m, and this is defined as a moderate altitude.
Intense physical activity at low altitudes is certainly a risk factor for rare complications, such as splenic infarction, sudden death, or rhabdomyolysis; rapid exposure to high altitudes and related hypoxia increase the frequency of splenic infarction episodes. In retrospective studies, over 90% of the cases of patients with splenic infarctions at high altitude were SCT and males.
In this context, hypoxia and physical stress are responsible for vaso-occlusion from sickling in the spleen red pulp. The splenic infarction of individuals affected by SCT is a benign condition that very rarely requires splenectomy and usually results in complete recovery with conservative therapies (rest, hydration, oxygen support, analgesics, and rapid patient transport to low altitudes).
Importantly, splenic infarction is not observed in SCT individuals who are native to or have been resident for many years in high-altitude locations; therefore, acclimation has a protective effect on sickling and its complications [28][29][30].
When individuals with SCT undertake sports activities of any kind at moderate altitudes or mountaineering at high altitudes, a specific acclimation program is recommended.
(B)
 High-pressure activities
There are no reports of complications following scuba diving. Regarding the physiology of diving (increased oxygen concentrations and possible toxicity), a minimum increase in risk can be supposed during nonprofessional practice. However, in relation to the complexity of the exercises undertaken in the navy, diving is not recommended for individuals with SCT [31].

This entry is adapted from the peer-reviewed paper 10.3390/jcm12103441

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