Sickle cell trait
Sickle cell trait | |
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Sickle cells in human blood: both normal red blood cells and sickle-shaped cells are present | |
Specialty | Hematology |
Sickle cell trait describes a condition in which a person has one abnormal
Sickle cell disease is a blood disorder wherein there is a single
Symptoms and signs
Sickle cell trait is a hemoglobin genotype AS and is generally regarded as a benign condition.
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]
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 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.[5]
Established associations
- Hematuria[6]
- Hyposthenuria[7]
- Renal medullary carcinoma, a cancer affecting the kidney, is a very rare complication seen in patients with sickle cell trait.[8]
- Renal papillary necrosis[6] (only considered "possible" by some sources)[9]
- Splenic infarcts at high altitude.[10] Surgery may not always be necessary.[11]
- Sudden deaths during physical exertion in African-American US army recruits, and athletes[12][13]
- Urinary tract infection[14]
Suggested
- Probable:preeclampsia
- Possible:[15] acute chest syndrome, asymptomatic bacteriuria, and anemia in pregnancy
- Insufficient evidence:
There have been reports of
Sickle cell trait appears to worsen the complications seen in
Genetics
Normally, a person inherits two copies of the
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]
Unlike the sickle-cell trait,
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]
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.
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 [clarification needed] 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. [20] [5] [21]
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
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.[25] 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.[26]
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.
Normal
The resulting microvasculatory distress in capillaries specific to muscle tissue can cause acute rhabdomyolysis and necrosis within the muscle cells.[28][29] 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.[30]
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.[27] 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.[25][27]
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.[31]
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.[27]
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.[29] 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]
A sickling collapse comes on slowly, following cramps, weakness, general body aches and fatigue.[29][30] 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.[32] Another common side effect or symptom is depression especially if the disease is left untreated.[33][failed verification]
A collapse can be prevented by taking steps to ensure sufficient oxygen levels in the blood. Among these preventative measures are proper hydration[25] and gradual acclimation to conditions such as heat, humidity, and decreased air pressure due to higher altitude.[28][29][32] Gradual progression of exertion levels also helps athletes' bodies adjust and compensate, gaining fitness slowly over the course of several weeks.[28][29][34]
See also
References
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- ^ 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/
- ^ Griffiths, Anthony JF; Gelbart, William M.; Miller, Jeffrey H.; Lewontin, Richard C. (1999). "Interactions Between the Alleles of One Gene". Modern Genetic Analysis.
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- ^ a b c d "ACSM and NCAA Joint Statement on Sickle Cell Trait and Exercise", NCAA.
- ^ a b c d e "Consensus Statement: Sickle Cell Trait and the Athlete", National Athletic Trainers' Association.
- ^ a b MedlinePlus Encyclopedia: Rhabdomyolysis
- ^ ""Sickle Cell Disease and Thalassemia", American Society of Hematology.
- ^ a b "Sickle Cell Disease Association of America, Inc". Archived from the original on 2016-07-29. Retrieved 2015-05-26.[full citation needed]
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- ^ "Sickle Cell Trait". MetroHealth. Archived from the original on October 23, 2017. Retrieved January 31, 2016.