Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Abstract

POINT-COUNTERPOINTCounterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activityPhilippe Connes, Marie-Dominique Hardy-Dessources, and Olivier HuePhilippe Connes, Marie-Dominique Hardy-Dessources, and Olivier HuePublished Online:01 Dec 2007https://doi.org/10.1152/japplphysiol.00338.2007aMoreSectionsPDF (52 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Sickle cell trait (SCT; or AS hemoglobinopathy) is the heterozygous form of sickle cell anemia and is present in over 2.5 million African Americans. Its prevalence can reach 20–40% in some areas of sub-Saharan Africa and 10% in the French West Indies (12). SCT is usually considered a benign disorder compared with sickle cell anemia (SS hemoglobinopathy; Ref. 27) and the longevity of SCT carriers seems to be unaffected (2).However, Kark and Ward (16) underlined that serious morbidity or mortality can result from complications related to polymerization of deoxy-HbS in SCT. Bergeron et al. (4) demonstrated that only 45 min of brisk walking at 33°C significantly increased erythrocyte sickling in SCT carriers when hydration was not sufficient to offset a body weight deficit that may contribute to the exertional heat illness sometimes reported in SCT (15, 16). Several cases of splenic infarction with altitude hypoxia or exercise, exertional heat illness (exertional rhabdomyolysis, heat stroke, or renal failure), or idiopathic sudden death have been described in SCT carriers (10, 14, 16, 17, 25). Wirthwein et al. (30) recently described three cases of young black individuals with no significant medical history who died following physical exertion. In all three cases, postmortem hemoglobin (Hb) electrophoresis demonstrated the presence of HbS. Kark et al. (15) demonstrated a substantially higher risk of exercise-related death unexplained by prior disease in Army, Air Force, Navy, and Marine Corps recruits with SCT from 1977 through 1981. Metabolic or environmental changes such as hypoxia, acidosis, dehydration, hyperosmolality, or hyperthermia may transform silent SCT into a syndrome resembling sickle cell disease with vaso-occlusive crisis due to an accumulation of low deformable red blood cells (RBCs) in the microcirculation (16). Although the causal relationship between SCT and these medical complications have not been directly demonstrated, these reports have introduced doubts about the medical status of SCT carriers and led Ajayi (1) to recently propose that SCT has been misclassified as benign and asymptomatic and should be reclassified as a disease state.Several studies have reported biological and clinical differences between SCT carriers and subjects with normal Hb that suggest that SCT carriers should be considered as symptomatic. Westerman et al. (29) demonstrated elevated d-dimers, thrombin-antithrombin complexes, and prothrombin fragments 1 and 2 in SCT carriers at rest, indicating that they may be prone to a hypercoagulable state in resting conditions. In addition, several reports have observed impaired RBC deformability at rest in this population using either a filtration method, optical tweezers, or a viscometer (5, 6, 23). The low RBC deformability observed in SCT carriers could be due to membrane disorganization related to abnormal interaction of HbS with the cell membrane and to dehydration promoted by higher activity of the RBC K+-Cl− cotransporter and monocarboxylate transporter (MCT-1; Refs. 6, 19, 24). Impaired RBC deformability may adversely affect capillary recruitment and the physiological mechanisms that ensure adequate delivery of oxygen to tissue (22). Low deformable RBCs cannot pass through the narrowest capillaries leading to plasma skimming (plasma flow without RBCs) and tissue ischemia (18). Therefore, SCT carriers are often marked by high blood viscosity in comparison with subjects with normal Hb (6, 7) that can cause blood flow structuring disorders in both the micro- and macrocirculation (3) and promote tissue hypoxia (9). These hemorheological alterations are also thought to explain why SCT carriers may be prone to asthma (21) and cardiac events (8, 20).Connes et al. (8) recently demonstrated that SCT carriers with high blood viscosity presented impaired nocturnal autonomic nervous system activity compared with subjects with normal Hb. A loss or imbalance of autonomic nervous system activity is a powerful and independent predictor of adverse prognosis in patients with heart disease, as well as in the general population (28). Therefore, SCT carriers might be more predisposed to cardiovascular complications than subjects with normal Hb (8), although older studies using more classical methods suggested normal cardiac function in this population at rest and during exercise (11, 13).The fatal events observed in SCT carriers often occur in response to exercise (10, 14–16). Senturk et al. (26) recently suggested that the often observed hemorheological alterations induced by exercise in healthy subjects could have deleterious effects on tissue perfusion, especially during the immediate recovery, because the hemodynamic enhancements of shear rates are rapidly reversed after the cessation of exercise. Thus the prolonged hemorheological changes that persist during recovery increase the risk of exercise-related morbidity and mortality (26). The picture of blood rheological changes induced by exercise was recently investigated in SCT carriers in air-conditioned conditions and showed higher blood viscosity and lower RBC deformability in this population compared with subjects with normal Hb, both at rest and during a short supramaximal exercise and the subsequent recovery (7). This may constitute a risk factor for microcirculatory disorders and cardiovascular complications in this group, especially during the recovery when blood flow returns to baseline value. Although the SCT carriers were marked by hemorheological alterations, exercise did not magnify the difference with the control group that already existed at rest because the pattern of hemorheological changes induced by exercise was exactly the same in the SCT carriers and control subjects. Therefore, the risk for health complications in SCT carriers in response to exercise is not really due to the hemorheological changes induced by exercise but rather to the pre-exercise hemorheological alterations that are amplified during exercise and the immediate recovery.These experimental data demonstrate that SCT carriers are marked by biological and clinical differences in comparison with subjects with normal Hb. Therefore, we do not agree with the assumption that SCT is asymptomatic. 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J Forensic Sci 46: 399–401, 2001.Crossref | ISI | Google Scholar Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Cited ByMicrofluidic concurrent assessment of red blood cell adhesion and microcapillary occlusion: potential hemorheological biomarkers in sickle cell disease1 January 2023 | Sensors & Diagnostics, Vol. 2, No. 2Lower Muscle and Blood Lactate Accumulation in Sickle Cell Trait Carriers in Response to Short High-Intensity Exercise24 January 2022 | Nutrients, Vol. 14, No. 3Does physical activity increase or decrease the risk of sickle cell disease complications?23 December 2015 | British Journal of Sports Medicine, Vol. 52, No. 4Impact du trait drépanocytaire sur la rigidité artérielle des sujets africainsJMV-Journal de Médecine Vasculaire, Vol. 42, No. 1Transgenic sickle cell trait mice do not exhibit abnormal thermoregulatory and stress responses to heat shock exposureBlood Cells, Molecules, and Diseases, Vol. 59Role of Exercise-Induced Oxidative Stress in Sickle Cell Trait and Disease14 December 2015 | Sports Medicine, Vol. 46, No. 5Athletes with Chronic Conditions: Sickle Cell Trait7 January 2016Blood viscosity is lower in trained than in sedentary sickle cell trait carriersClinical Hemorheology and Microcirculation, Vol. 61, No. 1Mechanical differences of sickle cell trait (SCT) and normal red blood cells1 January 2015 | Lab on a Chip, Vol. 15, No. 15Intraday Blood Rheological Changes Induced by Ramadan Fasting in Sickle Cell Trait Carriers5 August 2013 | Chronobiology International, Vol. 30, No. 9Évaluation de la déformabilité érythrocytaire des sujets porteurs de trait drépanocytaire au cours d’un match de football : effet de l’hydratation ad libitum20 March 2013 | Bulletin de la Société de pathologie exotique, Vol. 106, No. 2Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell traitLucile Vincent, Samuel Oyono-Enguéllé, Léonard Féasson, Viviane Banimbek, Macias Dohbobga, Cyril Martin, Patrice Thiriet, Alain Francina, Hervé Dubouchaud, Hervé Sanchez, Rachel Chapot, Christian Denis, André Geyssant, and Laurent Messonnier15 August 2012 | Journal of Applied Physiology, Vol. 113, No. 4Exercise training blunts oxidative stress in sickle cell trait carriersErica N. 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Boucher1 April 2008 | Journal of Applied Physiology, Vol. 104, No. 4Physiological Responses of Sickle Cell Trait Carriers during ExerciseSports Medicine, Vol. 38, No. 11Sickle cell trait should be considered asymptomatic and as a benign condition during physical activityOguz K. Baskurt, and Herbert J. Meiselman1 December 2007 | Journal of Applied Physiology, Vol. 103, No. 6 More from this issue > Volume 103Issue 6December 2007Pages 2138-2140 Copyright & PermissionsCopyright © 2007 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00338.2007aPubMed18056520History Published online 1 December 2007 Published in print 1 December 2007 Metrics