View source for Sickle cell trait

{{About|the genetic transmission of sickle-cell diseases|the disease itself|sickle-cell disease}}
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'''Sickle cell trait''' describes a condition in which a person has one abnormal [[allele]] of the [[hemoglobin beta]] [[gene]] (is [[heterozygous]]), but does not display the severe symptoms of [[sickle-cell disease|sickle cell disease]] that occur in a person who has two copies of that allele (is [[homozygous]]). Those who are heterozygous for the sickle cell allele produce both normal and abnormal hemoglobin (the two alleles are [[Dominance (genetics)#Co-dominance|codominant]] with respect to the actual concentration of hemoglobin in the circulating cells).

Sickle cell disease is a blood disorder wherein there is a single [[amino acid]] substitution in the hemoglobin protein of the [[red blood cells]], which causes these cells to assume a sickle shape, especially when under low [[oxygen tension]]. Sickling and sickle cell disease also confer some resistance to [[malaria]] parasitization of red blood cells, so that individuals with sickle-cell trait (heterozygotes) have a selective advantage in environments where malaria is present.

== Symptoms and signs ==
Sickle cell trait is a hemoglobin genotype AS and is generally regarded as a benign condition.<ref name="pmid16286558">{{Cite journal |last=Roach |first=E. S. |year=2005 |title=Sickle Cell Trait |journal=Archives of Neurology |volume=62 |issue=11 |pages=1781–2 |doi=10.1001/archneur.62.11.1781 |pmid=16286558}}</ref> However, individuals with sickle cell trait may have rare complications. For example, in November 2010, Dr. Jeffery K. Taubenberger of the [[National Institutes of Health]] discovered the earliest proof of sickle-cell disease while looking for the virus of the 1918 flu during the autopsy of an [[African-American]] soldier.  Taubenberger's autopsy results showed that the soldier had had a sickle-cell crisis that contributed to his death even though he had only one copy of the gene.<ref>{{Cite web |title=From 1918 Autopsy, A First Glimpse of Sickle Cell — and a Warning |url=https://www.wired.com/wiredscience/2010/11/from-a-1918-autopsy-a-first-glimpse-of-sickle-cell-%E2%80%94%C2%A0and-a-warning/ |website=www.wired.com}}</ref> There have been calls to reclassify sickle cell trait as a disease state, based on its malignant clinical presentations.<ref name="pmid16198915">{{Cite journal |last=Ajayi |first=A.A. Leslie |year=2005 |title=Should the sickle cell trait be reclassified as a disease state? |journal=European Journal of Internal Medicine |volume=16 |issue=6 |page=463 |doi=10.1016/j.ejim.2005.02.010 |pmid=16198915}}</ref> Significance may be greater during exercise.<ref name="pmid18937523">{{Cite journal |last=Connes |first=Philippe |last2=Reid |first2=Harvey |last3=Hardy-Dessources |first3=Marie-Dominique |last4=Morrison |first4=Errol |last5=Hue |first5=Olivier |year=2008 |title=Physiological Responses of Sickle Cell Trait Carriers during Exercise |journal=Sports Medicine |volume=38 |issue=11 |pages=931–46 |doi=10.2165/00007256-200838110-00004 |pmid=18937523 |s2cid=29469035}}</ref>

=== Association with other medical conditions ===

==== Malaria ====
The sickle cell trait provides a survival advantage against [[malaria]] fatality over people with normal hemoglobin in regions where malaria is endemic. The trait is known to cause significantly fewer deaths due to malaria, especially when ''[[Plasmodium falciparum]]'' is the causative organism. This is a prime example of [[natural selection]], evidenced by the fact that the geographical distribution of the gene for hemoglobin S and the distribution of malaria in Africa virtually overlap. Because of the unique survival advantage, people with the trait become increasingly numerous as the number of malaria-infected people increases. Conversely, people who have normal hemoglobin are more likely to succumb to the complications of malaria.{{citation needed|date=August 2015}}

The way in which sickle cell protects against malaria is attributed to several different things. One of the more common explanations is that the sickle hemoglobin inhibits the plasmodium parasite from infecting the red blood cells which reduces the number of malaria parasites to infect the host. Another factor is the production of [[HMOX1|heme oxygenase-1]] (HO-1) enzyme, which is highly present in the sickle hemoglobin. This enzyme produces carbon monoxide which has been proven to protect against cerebral malaria.<ref name="Ana Ferreira 2011">{{Cite journal |last=Ferreira |first=Ana |last2=Marguti |first2=Ivo |last3=Bechmann |first3=Ingo |last4=Jeney |first4=Viktória |last5=Chora |first5=Ângelo |last6=Palha |first6=Nuno R. |last7=Rebelo |first7=Sofia |last8=Henri |first8=Annie |last9=Beuzard |first9=Yves |last10=Soares |first10=Miguel P. |date=2011 |title=Sickle Hemoglobin Confers Tolerance to Plasmodium Infection |journal=Cell |language=en |volume=145 |issue=3 |pages=398–409 |doi=10.1016/j.cell.2011.03.049 |pmid=21529713 |s2cid=8567718 |doi-access=free}}</ref>

==== Established associations ====
* [[Hematuria]]<ref name="pmid9189873">{{Cite journal |last=Zadeii |first=Gino |last2=Lohr James W. |year=1997 |title=Renal Papillary Necrosis in a Patient with Sickle Cell Trait |url=http://jasn.asnjournals.org/cgi/pmidlookup?view=long&pmid=9189873 |journal=Journal of the American Society of Nephrology |volume=8 |issue=6 |pages=1034–9 |doi=10.1681/ASN.V861034 |pmid=9189873 |doi-access=free|url-access=subscription }}</ref>
* [[Hyposthenuria]]<ref name="pmid1752955">{{Cite journal |vauthors=Gupta AK, Kirchner KA, Nicholson R, etal |date=December 1991 |title=Effects of alpha-thalassemia and sickle polymerization tendency on the urine-concentrating defect of individuals with sickle cell trait |journal=J. Clin. Invest. |volume=88 |issue=6 |pages=1963–8 |doi=10.1172/JCI115521 |pmc=295777 |pmid=1752955}}</ref>
* [[Renal medullary carcinoma]], a cancer affecting the [[kidney]], is a very rare complication seen in patients with sickle cell trait.<ref>{{Cite journal |last=Davis |first=Charles J. |last2=Mostofi |first2=F. K. |last3=Sesterhenn |first3=Isabell A. |year=1995 |title=Renal Medullary Carcinoma The Seventh Sickle Cell Nephropathy |url=https://zenodo.org/record/1234748 |journal=The American Journal of Surgical Pathology |volume=19 |issue=1 |pages=1–11 |doi=10.1097/00000478-199501000-00001 |pmid=7528470 |s2cid=23101326}}</ref>
* [[Renal papillary necrosis]]<ref name="pmid9189873" /> (only considered "possible" by some sources)<ref name="Turgeon2005">{{Cite book |last=Mary Louise Turgeon |url=https://books.google.com/books?id=v2iyQBKx00kC&pg=PA179 |title=Clinical Hematology: Theory and Procedures |publisher=Lippincott Williams & Wilkins |year=2005 |isbn=978-0-7817-5007-3 |pages=179– |access-date=6 May 2010}}</ref>
* [[Splenic infarction|Splenic infarcts]] at high altitude.<ref name="Ghosh2008">{{Cite book |last=Amit K. Ghosh |url=https://books.google.com/books?id=B7xUKYrnUtMC&pg=PA425 |title=Mayo Clinic Internal Medicine Review: Eighth Edition |date=13 June 2008 |publisher=Informa Health Care |isbn=978-1-4200-8478-8 |pages=425– |access-date=6 May 2010}}</ref> Surgery may not always be necessary.<ref name="pmid16248136">{{Cite journal |last=Sheikha Anwar |year=2005 |title=Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary |journal=Canadian Journal of Surgery |volume=48 |issue=5 |pages=377–81 |pmc=3211898 |pmid=16248136}}</ref>
* Sudden deaths during physical exertion in African-American US army recruits, and athletes<ref name="pmid3627196">{{Cite journal |last=Kark |first=John A. |last2=Posey |first2=David M. |last3=Schumacher |first3=Harold R. |last4=Ruehle |first4=Charles J. |year=1987 |title=Sickle-Cell Trait as a Risk Factor for Sudden Death in Physical Training |journal=New England Journal of Medicine |volume=317 |issue=13 |pages=781–7 |doi=10.1056/NEJM198709243171301 |pmid=3627196}}</ref><ref name="pmid17393956">{{Cite journal |last=Mitchell |first=Bruce L. |year=2007 |title=Sickle Cell Trait and Sudden Death—Bringing it Home |journal=Journal of the National Medical Association |volume=99 |issue=3 |pages=300–5 |pmc=2569637 |pmid=17393956}}</ref>
* [[Urinary tract infection]]<ref name="Pace2007">{{Cite book |last=Betty Pace |url=https://books.google.com/books?id=mhqswaCtcLQC&pg=PA62 |title=Renaissance of Sickle Cell Disease Research in the Genome Era |publisher=Imperial College Press |year=2007 |isbn=978-1-86094-645-5 |pages=62– |access-date=6 May 2010}}</ref>

==== Suggested ====
* Probable:<ref name="pmid19393983">{{Cite journal |vauthors=Tsaras G, Owusu-Ansah A, Boateng FO, Amoateng-Adjepong Y |date=June 2009 |title=Complications associated with sickle cell trait: a brief narrative review |journal=Am. J. Med. |volume=122 |issue=6 |pages=507–12 |doi=10.1016/j.amjmed.2008.12.020 |pmid=19393983}}</ref> complicated [[hyphema]], [[venous thromboembolic events]], [[Miscarriage|fetal loss]], [[neonatal deaths]], and [[preeclampsia]]
* Possible:<ref name="pmid19393983" /> [[acute chest syndrome]], asymptomatic [[bacteriuria]], and [[anemia in pregnancy]]
* Insufficient evidence:<ref name="pmid19393983" /> [[retinopathy]], [[cholelithiasis]], [[priapism]],<ref name="pmid19116025">{{Cite journal |vauthors=Birnbaum BF, Pinzone JJ |year=2008 |title=Sickle cell trait and priapism: a case report and review of the literature |journal=Cases J |volume=1 |page=429 |doi=10.1186/1757-1626-1-429 |pmc=2628646 |pmid=19116025 |doi-access=free}}</ref> [[leg ulcers]], [[liver necrosis]], [[avascular necrosis of the femoral head]], and [[stroke]]. An association with complicated [[migraine]]s has been suggested.<ref name="pmid5031686">{{Cite journal |last=Osuntokun |first=B. O. |last2=Osuntokun |first2=O. |year=1972 |title=Complicated Migraine and Haemoglobin AS in Nigerians |journal=BMJ |volume=2 |issue=5814 |pages=621–2 |doi=10.1136/bmj.2.5814.621 |pmc=1788370 |pmid=5031686}}</ref>

There have been reports of [[pulmonary venous thromboembolism]] in pregnant women with sickle cell trait,<ref name="pmid17409269">{{Cite journal |vauthors=Austin H, Key NS, Benson JM, etal |date=August 2007 |title=Sickle cell trait and the risk of venous thromboembolism among blacks |journal=Blood |volume=110 |issue=3 |pages=908–12 |doi=10.1182/blood-2006-11-057604 |issn=0006-4971 |pmid=17409269 |s2cid=6604541 |doi-access=free}}</ref> or men during prolonged airflight, and mild strokes and abnormalities on PET scans in children with the trait.{{citation needed|date=December 2021}}

Sickle cell trait appears to worsen the complications seen in [[diabetes mellitus type 2]] ([[retinopathy]], [[nephropathy]] and [[proteinuria]])<ref name="pmid15450989">{{Cite journal |vauthors=Ajayi AA, Kolawole BA |date=August 2004 |title=Sickle cell trait and gender influence type 2 diabetic complications in African patients |journal=Eur. J. Intern. Med. |volume=15 |issue=5 |pages=312–315 |doi=10.1016/j.ejim.2004.06.003 |issn=0953-6205 |pmid=15450989}}</ref> and provoke [[hyperosmolar diabetic coma]] nephropathy, especially in male patients.

== Genetics ==
Normally, a person inherits two copies of the [[gene]] that produces [[beta-globin]], a [[protein]] needed to produce normal hemoglobin ([[hemoglobin A]], genotype AA). A person with sickle cell trait inherits one normal [[allele]] and one abnormal allele encoding hemoglobin S (hemoglobin genotype AS).{{citation needed|date=September 2021}}

The sickle cell trait can be used to demonstrate the concepts of co-dominance and incomplete dominance. An individual with the sickle cell trait shows incomplete dominance when the shape of the red blood cell is considered. This is because the sickling happens only at low oxygen concentrations. With regards to the actual concentration of hemoglobin in the circulating cells, the alleles demonstrate co-dominance as both 'normal' and mutant forms co-exist in the bloodstream. Thus it is an ambiguous condition showing both incomplete dominance and co-dominance.{{citation needed|date=September 2021}}

Unlike the sickle-cell trait, [[sickle-cell disease]] is passed on in a recessive manner. Sickle cell anemia affects about 72,000 people in the United States. Most Americans who have sickle cell anemia are of African descent. The disease also affects Americans from the [[Caribbean]], [[Central America]], and parts of [[South America]], [[Turkey]], [[Greece]], [[Italy]], the [[Middle East]] and East India.

Sickle-cell disease and the associated trait are most prevalent in Africa and Central America, which is attributed to natural selection:  the sickle-cell trait confers a survival advantage in areas with a high occurrence of malaria, which has a high death rate among individuals without the trait.{{citation needed|date=May 2022}}

There also have been studies that show changes in the globin genes. There have been noted changes in the beta-globin sequence, to what is known as the sickle hemoglobin.{{cn|date=October 2024}}

The significance of the sickle-cell trait is that it does not show any symptoms, nor does it cause any major difference in blood cell count. The trait confers about 30% protection against malaria {{clarify|date=November 2021}} and its occurrence appears to have risen tremendously in [[Africa]], [[India]] and the Middle East. Some findings also show the reduction of the sickle-cell trait in those who retain much more fetal hemoglobin than usual in adulthood. Fetal hemoglobin likely plays a role in the prevention of sickling. Elevated fetal hemoglobin levels have been observed in populations where sickle-cell disease is prevalent.
<ref>Pasricha,S.,Hall, W., Hall, E. (2018).How our red blood cells keep evolving to fight malaria. Quartzafrica, Retrieved from https://qz.com/africa/1450731/to-beat-malaria-red-blood-cells-keep-evolving-like-sickle-cell/</ref>
<ref name="Ana Ferreira 2011" />
<ref>{{Cite journal |last=Griffiths |first=Anthony JF |last2=Gelbart |first2=William M. |last3=Miller |first3=Jeffrey H. |last4=Lewontin |first4=Richard C. |year=1999 |title=Interactions Between the Alleles of One Gene |url=https://www.ncbi.nlm.nih.gov/books/NBK21226 |journal=Modern Genetic Analysis}}</ref>

Whole genome sequence analysis has identified a single origin of the sickle trait, with one haplotype ancestral to all sickle-cell variants. This haplotype is thought to have originated in the Sahara during the [[Holocene Wet Phase]] around 7,300 years ago. Sickle cell variants descended from this ancestral haplotype comprise five haplotypes named after toponyms or ethnolinguistic groups (the Arabian/Indian, [[Benin]], [[Cameroon]], [[Central African Republic]]/[[Bantu languages|Bantu]], and [[Senegal]] variants), and another designation earmarked for atypical sickle-cell haplotypes.<ref>{{Cite bioRxiv |biorxiv=10.1101/187419 |author=Daniel Shriner |author2=Charles N. Rotimi |title=Whole genome sequence-based haplotypes reveal single origin of the sickle allele during the 2 Holocene Wet Phase}}</ref><ref>{{Cite book |last=Okpala |first=Iheanyi |url=https://books.google.com/books?id=EKrzg_DoSFcC |title=Practical Management of Haemoglobinopathies |date=2008 |publisher=John Wiley & Sons |isbn=978-1-4051-4020-1 |page=21 |access-date=2 June 2016}}</ref> Their clinical importance is because some are associated with higher HbF levels (e.g., Senegal and Saudi-Asian variants tend to have milder disease).<ref name="pmid7505527">{{Cite journal |vauthors=Green NS, Fabry ME, Kaptue-Noche L, Nagel RL |date=Oct 1993 |title=Senegal haplotype is associated with higher HbF than Benin and Cameroon haplotypes in African children with sickle cell anemia |journal=Am. J. Hematol. |volume=44 |issue=2 |pages=145–6 |doi=10.1002/ajh.2830440214 |issn=0361-8609 |pmid=7505527 |s2cid=27341091}}</ref>

== In athletes ==

In some cases, athletes with sickle cell trait do not achieve the same level of performance as elite athletes with normal hemoglobin (AA). Athletes with sickle cell trait and their instructors must be aware of the dangers of the condition during anaerobic exertion especially in hot and dehydrated conditions.<ref name="pmid20581085" /> In rare cases, exercise-induced dehydration or exhaustion may cause healthy red blood cells to turn sickle-shaped, which can cause death during sporting activities.<ref name="pmid17923725">{{Cite journal |last=Eichner |first=ER |year=2007 |title=Sickle cell trait |journal=Journal of Sport Rehabilitation |volume=16 |issue=3 |pages=197–203 |doi=10.1123/jsr.16.3.197 |pmid=17923725}}</ref>

While more research is necessary on the topic, the correlation found between individuals with sickle cell trait and an increased risk of sudden death appears to be related to microcirculatory disorders, during exercise.<ref name="pmid16015123">{{Cite journal |last=Monchanin |first=Geraldine |last2=Connes |first2=Philippe |last3=Wouassi |first3=Dieudonne |last4=Francina |first4=Alain |last5=Djoda |first5=Bernard |last6=Banga |first6=Pierre Edmond |last7=Owona |first7=Francois Xavier |last8=Thiriet |first8=Patrice |last9=Massarelli |first9=Raphael |last10=Martin |first10=Cyril |year=2005 |title=Hemorheology, Sickle Cell Trait, and α-Thalassemia in Athletes: Effects of Exercise |journal=Medicine and Science in Sports and Exercise |volume=37 |issue=7 |pages=1086–92 |doi=10.1249/01.mss.0000170128.78432.96 |pmid=16015123 |doi-access=free}}</ref> In recent years the [[NCAA]] has partnered with the [[American College of Sports Medicine|ACSM]] and issued a joint statement, warning athletes about both the prevalence and the potential risk factors of sickle cell trait.<ref name="ncaa.org acsm-and-ncaa-joint-statement-sickle-cell-trait-and-exercise">[https://www.ncaa.org/health-and-safety/medical-conditions/acsm-and-ncaa-joint-statement-sickle-cell-trait-and-exercise "ACSM and NCAA Joint Statement on Sickle Cell Trait and Exercise"], NCAA.</ref>  The NCAA has also recently encouraged athletes to become aware of their sickle cell trait status, as the trait itself does not typically result in symptoms under normal conditions but can become dangerous during extreme physical activity similar to the daily training that athletes undergo.{{citation needed|date=September 2021}}

Normal [[hemoglobin]] (and hemoglobin S in the presence of oxygen) contains a [[Erythrocyte deformability|deformability]] characteristic that allows [[erythrocytes]] to essentially squeeze their way into smaller vessels, including those involved in [[microcirculation]] to the [[capillaries]] within muscle tissue as well as blood supply embedded within organ tissues.  When hemoglobin S is deprived of oxygen, it can polymerize, which is what is proposed to cause the "sickled" cells.<ref name="pmid16015123" /> The sickled erythrocytes present a decreased deformability when compared to normal erythrocytes, leading to distress in circulation into the smaller vessels involved in microcirculation, particularly, in this case, the capillaries embedded in muscle tissue.{{citation needed|date=September 2021}}

The resulting microvasculatory distress in capillaries specific to muscle tissue can cause acute [[rhabdomyolysis]] and [[necrosis]] within the muscle cells.<ref name="ncaa.org acsm-and-ncaa-joint-statement-sickle-cell-trait-and-exercise" /><ref name="nata.org SickleCellTraitAndTheAthlete">[http://www.nata.org/sites/default/files/SickleCellTraitAndTheAthlete.pdf "Consensus Statement: Sickle Cell Trait and the Athlete"], National Athletic Trainers' Association.</ref> The inflammation and leakage of intracellular material resulting from muscle cell necrosis releases a particular protein, [[myoglobin]], into the blood stream.  While necessary in muscle tissue to bind iron and oxygen, myoglobin circulating through the bloodstream can break down into smaller compounds that damage kidney cells, leading to various complications, such as those seen in sickle cell trait athletes during high levels of physical exertion.<ref name="MedlinePlusEncyclopedia000473">{{MedlinePlusEncyclopedia|000473|Rhabdomyolysis}}</ref>

Because of the link between deformability and sickled cells, deformability can be used to evaluate the amount of sickled cells in the blood.  Deformability of the erythrocytes that cause the microcirculatory distress can be demonstrated through various other hemorheological characteristics.<ref name="pmid16015123" /> In order to determine the deformability of erythrocytes multiple factors including blood and plasma viscosity and hematocrit (a calculation of the percent of red blood cells present in the blood) are measured.<ref name="pmid20581085" /><ref name="pmid16015123" />

=== Alpha-thalassemia ===
[[Alpha-thalassemia]], like sickle cell trait, is typically inherited in areas with increased exposure to malaria. It manifests itself as a decreased expression of alpha-globin chains, causing an imbalance and excess of beta-globin chains, and can occasionally result in anemic symptoms.  The abnormal hemoglobin can cause the body to destroy red blood cells, essentially causing anemia.<ref>[http://www.hematology.org/About/History/50-Years/1534.aspx ""Sickle Cell Disease and Thalassemia"],  American Society of Hematology.</ref>

In endurance-trained individuals with sickle cell trait the presence of alpha-thalassemia has been shown to act protectively against microvasculatory distress before, during, and after exercise.<ref name="pmid16015123" />

=== Signs, symptoms, and prevention ===
Because of the microcirculatory distress, a telltale sign or symptom of a potential sickling collapse is cramping.  Specifically to sickle cell trait, cramping occurs in the lower extremities and back in athletes undergoing intense physical activity or exertion.<ref name="nata.org SickleCellTraitAndTheAthlete" /> In comparison to heat cramps, sickling cramps are less intense in terms of pain and have a weakness and fatigue associated with them, as opposed to tightly contracted muscles that lock up during heat cramps.{{citation needed|date=September 2021}}

A sickling collapse comes on slowly, following cramps, weakness, general body aches and fatigue.<ref name="nata.org SickleCellTraitAndTheAthlete" /><ref name="MedlinePlusEncyclopedia000473" /> Individuals with known positive sickle cell trait status experiencing significant muscle weakness or fatigue during exercise should take extra time to recover and hydrate before returning to activity in order to prevent further symptoms.<ref name="sicklecelldisease.org sickle-cell-trait-athletics">{{Cite web |title=Sickle Cell Disease Association of America, Inc |url=http://www.sicklecelldisease.org/index.cfm?page=sickle-cell-trait-athletics |archive-url=https://web.archive.org/web/20160729221708/http://www.sicklecelldisease.org/index.cfm?page=sickle-cell-trait-athletics |archive-date=2016-07-29 |access-date=2015-05-26}}{{full citation needed|date=August 2015}}</ref> Another common side effect or symptom is depression especially if the disease is left untreated.<ref>{{Cite journal |last=Jenerette |first=Coretta |last2=Funk |first2=Marjorie |last3=Murdaugh |first3=Carolyn |date=January 2005 |title=Sickle Cell Disease: A Stigmatizing Condition That May Lead to Depression |url=http://www.tandfonline.com/doi/full/10.1080/01612840500280745 |journal=Issues in Mental Health Nursing |language=en |volume=26 |issue=10 |pages=1081–1101 |doi=10.1080/01612840500280745 |issn=0161-2840 |pmid=16284000|url-access=subscription }}</ref>{{Failed verification|date=March 2024|reason=Source appears to be about sickle cell disease, not sickle cell trait}}

A collapse can be prevented by taking steps to ensure sufficient oxygen levels in the blood.  Among these preventative measures are proper hydration<ref name="pmid20581085">{{Cite journal |last=Tripette |first=J. |last2=Loko |first2=G. |last3=Samb |first3=A. |last4=Gogh |first4=B. D. |last5=Sewade |first5=E. |last6=Seck |first6=D. |last7=Hue |first7=O. |last8=Romana |first8=M. |last9=Diop |first9=S. |last10=Diaw |first10=M. |last11=Brudey |first11=K. |last12=Bogui |first12=P. |last13=Cisse |first13=F. |last14=Hardy-Dessources |first14=M.-D. |last15=Connes |first15=P. |year=2010 |title=Effects of hydration and dehydration on blood rheology in sickle cell trait carriers during exercise |journal=AJP: Heart and Circulatory Physiology |volume=299 |issue=3 |pages=H908–14 |doi=10.1152/ajpheart.00298.2010 |pmid=20581085 |s2cid=20311789}}</ref> and gradual acclimation to conditions such as heat, humidity, and decreased air pressure due to higher altitude.<ref name="ncaa.org acsm-and-ncaa-joint-statement-sickle-cell-trait-and-exercise" /><ref name="nata.org SickleCellTraitAndTheAthlete" /><ref name="sicklecelldisease.org sickle-cell-trait-athletics" /> Gradual progression of exertion levels also helps athletes' bodies adjust and compensate, gaining fitness slowly over the course of several weeks.<ref name="ncaa.org acsm-and-ncaa-joint-statement-sickle-cell-trait-and-exercise" /><ref name="nata.org SickleCellTraitAndTheAthlete" /><ref>{{Cite web |title=Sickle Cell Trait |url=https://metrohealth.net/healthwise/sickle-cell-trait/ |url-status=dead |archive-url=https://web.archive.org/web/20171023230421/https://metrohealth.net/healthwise/sickle-cell-trait/ |archive-date=October 23, 2017 |access-date=January 31, 2016 |website=MetroHealth}}</ref>

== See also ==
* [[Ryan Clark (American football)]]

== References ==
{{Reflist}}

== External links ==
{{Medical resources
|  DiseasesDB     =
|  ICD10          = {{ICD10|D|57|3|d|55}}
|  ICD9           = {{ICD9|282.5}}
|  ICDO           =
|  OMIM           = 603903
|  MedlinePlus    = 000527
|  eMedicineSubj  = search
|  eMedicineTopic = Sickle%20cell
|  MeshID         = D012805
}}
{{Diseases of RBCs}}

[[Category:Hereditary hemolytic anemias]]
[[Category:Autosomal recessive disorders]]
[[Category:Health in Africa]]
[[Category:Disorders of globin and globulin proteins]]