The present study compared the changes in blood viscosity, hydration status, body temperature and heart rate between a group of sickle cell trait (SCT) carriers and a control (Cont) group before and after a soccer game performed in two conditions: one with water offered ad libitum (hydration condition; Hyd) and the other one without water (dehydration condition; Dehyd). Blood viscosity and haematocrit per blood viscosity ratio (HVR; an index of red blood cell oxygen transport effectiveness) were measured before and at the end of each game. Resting blood viscosity was greater in the SCT carriers than in the Cont group. The increase of blood viscosity over baseline at the end of the game in the Cont group was similar in the two conditions. In contrast, the change in blood viscosity occurring in SCT carriers during soccer games was dependant on the experimental condition: (1) in Dehyd condition, blood viscosity rose over baseline; (2) in Hyd condition, blood viscosity decreased below resting level reaching Cont values. The Cont group had higher HVR than SCT carriers at rest. HVR remained unchanged in the Cont group at the end of the games, whatever the experimental condition. Although HVR of SCT carriers decreased below baseline at the end of the game performed in Dehyd condition, it increased over resting level in Hyd condition reaching the values of the Cont group. Our study demonstrated that ad libitum hydration in exercising SCT carriers normalises the blood hyperviscosity.
Statistics from Altmetric.com
Sickle cell trait (SCT) is the heterozygous form of sickle cell anaemia and is common in Afro–Americans, inhabitants of the Caribbean Islands and African countries. Although SCT is considered a benign condition, this notion is somewhat challenged by the literature as there have been multiple articles that raise an association with sudden death and long-term disease risk.1,–,3 SCT carriers are typically asymptomatic in comparison with people with sickle cell anaemia or sickle cell haemoglobin C disease. Nevertheless, several authors have questioned the benign character of SCT carriers, notably in certain scenarios of physical effort.3,–,5 Epidemiological data from the US Army demonstrated that the risk for exercise-related sudden death unexplained by pre-existing disease was 30 times greater in black recruits with SCT than in black recruits without SCT.3 This association between SCT and increased risk of exertional death has been recently re-confirmed by Harmon et al2 in National Collegiate Athletic Association (NCAA) Division I football players with SCT athletes having a 37 times greater risk than non-SCT athletes. It has been recently proposed that the haemorheological abnormalities described in SCT carriers, both at rest and in response to exercise,6,–,11 could increase the risks for microcirculatory alterations that could ultimately cause impaired tissue perfusion at the level of several organs and notably exercising muscles.12 Indeed, several cases of fulminant rhabdomyolysis have been reported in exercising SCT carriers.13 ,14
Exposure to a warm-to-hot environment and dehydration could play an important role in the occurrence of adverse events in exercising SCT carriers.5 ,15 It has been hypothesised that adequate hydration and simple precautions, such as wearing light clothing or starting exercise and progressing gradually could reduce the risks for adverse events during exercise.16 Two studies only, conducted in laboratory conditions, have tested and demonstrated the efficiency of hydration during exercise on some biological abnormalities of SCT carriers.11 ,17 Bergeron et al17 demonstrated in SCT carriers (N=2) that a brisk walking exercise of 45 min duration in hot environment and without drinking any fluid during or for 3 h prior to exercise increased the percentage of sickle red blood cells (RBC); but, this increase was offset when subjects drank water before and during the effort. More recently, Tripette et al11 reported that the marked resting hyperviscosity of SCT carriers was completely normalised after a moderate cycling exercise of 40 min duration when ad libitum hydration was made possible; which was not the case in the situation where no water intake was made available.
However, the exercise protocols proposed in these two studies11 ,17 as well as in the other studies which looked at the changes in biological parameters,6 ,18 do not reflect a practical exercise condition where adverse events could occur in SCT carriers. Indeed, to better reflect the exercise and environmental conditions where SCT carriers could be susceptible to make complications, we investigated the effects of hydration and dehydration on the blood rheological profile of SCT carriers and control subjects before and after a soccer game. Since the important rise of blood viscosity previously reported in exercising SCT carriers could increase the risks for vascular complications, we hypothesised that hydration could limit this risk by normalising the blood hyper viscosity.
Materials and methods
Subjects and protocol
The study took place at Iba Mar Diop stadium in Dakar, in February. Twenty-two black male students (25.0±2.2 years, 65.0±5.5 kg, 175±8 cm) from the Higher National Institute of Popular Education and Sport in Dakar participated in this study: 11 SCT carriers and 11 subjects without haemoglobinopathy (control group; Cont). All subjects were sportsmen (>10 h of team sports/week) and practiced both football and basketball for the same duration per week.
The presence and the absence of abnormal haemoglobin (HbS) in SCT carriers and Cont group, respectively, were confirmed by HbS electrophoresis (mean value in SCT group: 36.9±3.5%). The subjects were informed of the procedures and purposes of the study, which was approved by the National Ethics Committee of Senegal, and gave written informed consent to participate. The protocol was in accordance with the guidelines set by the Declaration of Helsinki.
Subjects were then distributed randomly into two teams: (1) team A: six controls (with goalkeeper) and five SCT carriers; (2) team B: six SCT carriers (with goalkeeper) and five controls.
Both teams competed during two soccer games of 90 min duration and separated by 2 weeks. The environmental conditions were identical for both games (temperature: 76.1°F–77°F and humidity: 65%–68%) and were not warm. The players did not make any strenuous physical activity within the three preceding days of the soccer games, that is, no physical training and no sport competition. For each game, one of the two teams was allowed to drink water ad libitum (hydration condition; Hyd) whereas the other one was deprived of water (dehydration condition; Dehyd). Each player performed a soccer game in the two conditions: Hyd and Dehyd.
The volume of water ingested during the Hyd condition was evaluated after the game for each subject by measuring the remaining volume of water in precalibrated plastic bottles. The rectal temperature (RT) was measured (YSI thermistor thermometer, Yellow Springs Instrument, Yellow Springs, Ohio, USA) at rest and immediately after the games. Heart rate (HR) was measured continuously (SD 200, Polar Electo, Kempele, Finland) in six SCT carriers and six Cont subjects during the games performed in Hyd and Dehyd conditions. Urine specific gravity was investigated at rest and at the end of the games in the two groups (Roche Urisys 1100 urine Analyzer). The subjects were dehydratedand weighed naked and dry before and at the end of the games.
Haematocrit and blood viscosity measurements
Blood was sampled before and immediately at the end of the soccer games in one EDTA tube (4.5 ml). Blood viscosity (ηb) was measured with a cone-plate viscometer (Brookfield Pro DV II+, with CPE40 spindle) at high shear rate (225/s), at 37°C and in accordance with the recent international guidelines for the standardisation of haemorheological techniques.19 Haematocrit (Hct) was measured by micromethod after blood microcentrifugation (Jouan-Hema-C, Saint Herblain, France) at 1500 g for 5 min at room temperature (25°C). The ratio Hct/ηb (haematocrit per blood viscosity ratio – HVR) was calculated. The blood oxygen content increases linearly with Hct. However, the same increase of Hct causes an exponential rise of blood viscosity that, in turn, may decrease blood flow and tissue oxygenation. Indeed, the HVR index represents a balanced view of these two opposite effects of increased Hct and may be defined as an index of red blood cell oxygen transport effectiveness.20
All results are expressed as means±SD. Subject characteristics and the volume of water ingested during the Hyd condition were compared between the two groups using an unpaired Student's t test. Haemorheological parameters, RT, urine specific gravity, HR and weight were compared at rest and at the end of the game between the two groups in the two experimental conditions using a two-way analysis of variance with repeated measures. The significance level was defined as p<0.05. Analyses were conducted using Statistica (v. 5.5, Statsoft, Tulsa, Oklahoma, USA).
Subject characteristics and HR
As shown in the table 1, although SCT carriers tended to be slightly lighter than Cont subjects, no significant difference between Cont and SCT subjects was observed for anthropometric parameters.
The figure 1 shows the HR at rest and during the games performed in Hyd and Dehyd conditions for six SCT carriers and six controls. At rest, no significant difference was observed between the groups and conditions (figure 1). HR increased significantly above baseline with exercise in the two groups and in the two conditions, without any difference between the groups and conditions.
The weight of subjects decreased with exercise in the two groups and in the two conditions (table 2). The percentage of weight loss in the Cont group was −0.5±0.4% and −2.6±0.9% in Hyd and Dehyd conditions, respectively. The percentage of weight loss in SCT carriers was −0.6±0.5% and −3.3±0.6% in Hyd and Dehyd conditions, respectively.
The volume of water ingested in the Hyd condition did not differ between the two groups and was 1050±369 ml and 1150±340 ml in the Cont and SCT group, respectively. RT increased significantly over baseline at the end of the game performed in Dehyd condition in the two groups but remained statistically unchanged in Hyd condition. At the end of the soccer games, RT in Dehyd condition was greater than in Hyd condition in the two groups (table 2). At rest, urine specific gravity was not significantly different between the two groups (table 2). Urine specific gravity remained unchanged at the end of the game in Hyd condition. In Dehyd condition, the urine specific gravity of the SCT group at the end of the game was greater than resting level. The increase of urine specific gravity in the Cont group during the soccer game performed in Dehyd condition did not reach statistical significance (p=0.06). At the end of the games, urine specific gravity was greater in SCT Dehyd compared with SCT Hyd and Cont Hyd.
Haematocrit (Hct) is presented in table 2 and did not differ between the groups at rest. Hct increased significantly with exercise in the two groups in Dehyd Condition and remained statistically unchanged in Hyd condition. No significant difference between the two groups and the two conditions was observed at the end of the game.
The resting ηb of the SCT group was higher than ηb of the Cont group (figure 2). The ηb increased with exercise in the Cont group in the two conditions and in the SCT group in Dehyd condition only (figure 2 and figures 3A–C). In contrast, ηb decreased significantly below baseline in SCT carriers during the Hyd condition and reached the values of the Cont group in the two conditions (figures 2 and 3D). At the end of the soccer games, SCT group in Dehyd condition had higher ηb than other groups.
HVR was lower in the SCT group than in the Cont group at rest. HVR remained unchanged by exercise in the Cont group irrespective of the experimental condition (figure 4). In contrast, HVR decreased significantly with exercise in SCT carriers during the Dehyd condition. However, when hydrated, HRV of SCT carriers increased above baseline reaching the same values than Cont group in the two conditions. At the end of the game, HRV of the SCT group in Dehyd condition was below the values of the three other groups.
The main finding of the present study was the marked effect of ad libitum hydration on ηb and HVR in exercising SCT carriers: the high-resting ηb and low-resting HVR of SCT carriers were normalised at the end of the soccer game performed with hydration.
Exercise responses and hydration status
The body weight loss in SCT and Cont groups during the Dehyd condition was greater than 2% indicating marked dehydration.21 Nevertheless, because central volume is usually well maintained with such a small level of hydration, the cardiac responses did not differ between Hyd and Dehyd conditions in the two groups. As recommended, the hydration level of the subjects was also evaluated by using urine specific gravity measurements.22 At rest, the mean urine specific gravity of the groups was close to 1.020 g/ml which is considered as a sign of euhydration.21 Nevertheless, pregames urine specific gravity values were higher than 1.020 g/ml in 55% (6/11 players) and 45% (5/11 players) of the Cont group during the Dehyd and Hyd conditions, respectively, and in 30% (3/11 players) and 36% (4/11 players) of the SCT group during the Dehyd and Hyd conditions, respectively, indicating an important proportion of dehydrated subjects. These findings are in agreement with the study of Stover et al23 and Osterberg et al24 who reported that 46% of recreational athletes and 52% of the National Basketball Association players, respectively, were dehydrated. Though urine specific gravity remained unchanged in the two groups at the end of the soccer game performed in Hyd condition, the urine specific gravity exceeds the normal limit for defining dehydration21 in the two groups at the end of the soccer game performed in Dehyd condition. Although no significant difference in urine specific gravity was observed between SCT Dehyd and Cont Dehyd at the end of the game, the increase of urine specific gravity between rest and the end of game was statistically significant in the SCT carriers only, suggesting a slightly greater impact of water deprivation on the hydration status of SCT carriers. Nevertheless, the RT in the Dehyd condition was moderately elevated at the end of the game in SCT carriers with values comparable to those found in the Cont group. Indeed, it appears that the physiological stress of dehydration did not differ between the SCT and Cont groups.
Haemorheology at rest
Blood viscosity was higher at rest in SCT carriers than in the Cont group. Since plasma viscosity (data not shown) and Hct were not different between the two groups whatever the condition, the difference in ηb would have been related to the slightly reduced resting red blood cell deformability, as previously demonstrated.7 ,9 Although most of the haemorheological alterations usually found in SCT carriers may be considered as subclinical,20 ηb values can be as high as in patients with sickle cell HbSC disease who are known to develop frequent thromboembolic complications. In support of this, the results from Austin et al1 suggest that SCT is a risk factor for venous thromboembolism. Population with elevated baseline ηb values and low HVR at rest have been proposed as potentially at risk for microcirculatory disorders.7 ,25 ,26 We suggest that the hydration levels should be carefully controlled in SCT carriers and strategies to normalise their ηb could be beneficial for their health.
Effect of soccer games and hydration/dehydration on haemorheology
The increase of ηb in the Cont group after the soccer game performed in the two experimental conditions is in agreement with previous studies reporting an increase of ηb with exercise.27 ,28 Nevertheless, the lack of significant difference between Hyd and Dehyd conditions in the Cont group is surprising. It indicates that moderate dehydration does not exert any adverse effects on the blood viscosity of exercising athletes with normal Hb which confirms previous finding from Tripette et al.11
In contrast, it appears that water hydration played a very important role on the viscosity properties of blood in the exercising SCT carriers: ηb was normalised in the SCT group at the end of the soccer game when hydration was provided. However, when SCT carriers performed the soccer game in Dehyd condition, their ηb increased and their HVR decreased above/below baseline (+16.3±1.3% and −8.3±1.9%, respectively) at the end of the soccer game. The haemorheological benefits of hydration in exercising SCT carriers found in the present study strengthen the previous findings of Tripette et al11 who also demonstrated that ad libitum hydration was able to correct the haemorheological abnormalities of SCT carriers during a submaximal cycling exercise of 40 min duration. Nevertheless, the present results also demonstrated that when SCT carriers are deprived of water, their ηb/HVR may further rise/decrease above/below the values found in non-SCT subjects. In this situation, blood flow microcirculatory strain could be majored in SCT carriers.6 The underlying mechanisms of this wide blood viscosity increase in dehydrated SCT carriers have not been addressed specifically in this study. The same Hct and plasma viscosity (data not shown) responses in Cont and SCT groups under dehydration support that other factors than these could be involved. Sickling RBCs have been visualised on blood smears (data not shown) and it appears that less than 1/1000 sickle RBCs was found at rest or after the soccer games in SCT carriers both in Hyd and Dehyd conditions. Indeed, sickling process was probably not involved in the wide increase of blood viscosity in SCT carriers at the end of the game performed in Dehyd condition. Changes in RBC deformability may occur in SCT carriers without any sickling process.11 Indeed, we suspect that hydration had normalised the slightly reduced RBC deformability of SCT carriers (not assessed in this study)11 causing a normalisation of blood viscosity at the end of the game, despite the physiological stress of exercise. In contrast, RBC deformability of SCT carriers could have been slightly altered at the end of the game performed in Dehyd condition causing a further increase in blood viscosity. For technical reasons, the present study did not screen for the presence of α-gene deletions in SCT carriers. Since the association of α-thalassemia may modulate the biophysical properties of RBC from SCT carriers,29 further studies are needed to test the effects of α-thalassemia on the exercise haemorheological responses of hydrated/dehydrated SCT carriers.
SCT carriers should be encouraged to hydrate adequately during physical efforts. This statement is in agreement with the positions of the American Society of Hematology (ASH) and of the Sickle Cell Disease Association of America (SCDAA) which both support the implementation of universal guidelines to reduce dehydration and heat- or exercise-related illness in SCT carriers, as well as in non-SCT carriers.30 In contrast, both the ASH and SCDAA do not support the NCAA position which required all Division I schools to screen athletes or have them to sign a waiver declining the screen, if the athletes' SCT status was not already known from neonatal birth screening. The SCDAA recommends SCT testing should be done on a voluntary basis to avoid stigmatisation and genetic discrimination. Until now, it is unknown whether more aggressive implementation of universal guidelines and/or SCT screening could be efficient strategies to limit exercise-related sudden death in SCT carriers.
Although haemorheological abnormalities (ie, blood hyperviscosity and low HVR) were observed in SCT carriers after the game performed in Dehyd condition, their isolated interpretation is difficult. Recent findings support the viewpoint that having elevated blood viscosity might not always be detrimental for the cardiovascular system and health if the vascular system is able to adapt.28 ,31 Recently, in healthy subjects, it was demonstrated that the increase in ηb induced by exercise could be a way to increase shear stress and stimulate vasodilation through a nitric oxide–dependent mechanism, thereby promoting adequate oxygen delivery to tissues.32 Unfortunately, endothelial function or flow-mediated dilation were not evaluated in the present study. Indeed, although the blood rheological profile of SCT carriers is very different from the one of controls, particularly when dehydrated, the confirmation that blood viscosity could be involved in the increased risks of exercising sudden death in this population requires further studies.
What this study adds
Ad libitum hydration in exercising sickle cell trait carriers is able to fully normalise the haemorheological alterations of this population and may play a role in reduced clinical risk; however, further study specifically addressing this is warranted.
Recently, two studies demonstrated that physical fitness/regular training is able to positively modulate the inflammatory and oxidative stress responses of exercising SCT carriers.33 ,34 It is unknown whether regular training may influence the blood rheology of SCT carriers as it is the case for non-SCT carriers,27 ,28 but Aufradet et al33 and Chirico et al34 concluded that regular training could limit the risks for microcirculatory and vascular alterations in exercising SCT carriers and, as a consequence, limit the risks for exercise-related complications.33 ,34 Although physical fitness has been suggested to play a role in the exercise-related sudden death reported in the US army,15 it seems to be less the case in civilians.2 The assessment of the impact of physical fitness on the haemorheological responses in exercising SCT carriers needs further studies.
In summary, this study demonstrated that ad libitum hydration in exercising SCT carriers is able to normalise the haemorheological abnormalities of this population. Although the exact role of the blood rheological changes induced by exercise on the vascular function of SCT carriers is unknown, we suggest that SCT carriers should be encouraged to adequately drink during physical efforts.
Competing interests None.
Ethics approval The National Ethics Committee of Senegal.
Provenance and peer review Not commissioned; externally peer reviewed.
▸ References to this paper are available online at http://bjsm.bmj.com
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.