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Sickle Cell Trait

Hemoglobinopathy

Sickle cell trait is a heterozygous condition of the hemoglobin S (HbS) gene, making the person HbAS. It is a benign carrier condition, usually with none of the symptoms of sickle cell anemia. The erythrocytes of such individuals contain both normal adult hemoglobin (HbA) and HbS, but there is always more HbA than HbS.


Presentation

Sickle cell trait is usually asymptomatic. Anemia and painful crises are exceedingly rare. Papillary necrosis may cause painless hematuria in young males, though not a common presentation. Isosthenuria is a more common manifestation of the same process. High altitude exposure and extreme dehydration or exercise can rarely lead to sudden death. Urethral obstruction due to papillary sloughing is noted in few cases. Sickle cell trait is occasionally associated with exertional rhabdomyolysis and rarely with renal medullary cancer [6] [7].

Chest Discomfort
  • Patient made regular progress through CR, although continued to experience paroxysmal chest discomfort away from CR, which he denied having during exercise.[ncbi.nlm.nih.gov]
Gingival Recession
  • The clinical parameters evaluated were plaque index, gingival index, calculus index, clinical probing depth, clinical attachment level, gingival recession, tooth mobility and furcation involvement.[ncbi.nlm.nih.gov]
Protein S Deficiency
  • Association of mild protein S deficiency with erythrocytosis could have precipitated the onset of priapism.[ncbi.nlm.nih.gov]
Neglect
  • Our study highlights the need for further investigation of thalassemia, haemoglobinopathies that are neglected in sub-Saharan Africa.[ncbi.nlm.nih.gov]
  • Sickle cell trait—neglected opportunities in the era of genomic medicine. JAMA. 2014;311(15):1495–6. doi: 10.1001/jama.2014.2157 . CrossRef PubMed Google Scholar 63. Kengne AP, Echouffo-Tcheugui JB, Sobngwi E, Mbanya JC.[link.springer.com]
  • Although HbSC disease is one of the commonest significant genetic diseases worldwide, it is comparatively neglected with very few laboratory or clinical studies addressing the condition directly.[hindawi.com]
Sensory Deficit of the Lower Extremity
  • A few hours after surgery, the patient developed an acute paraplegia of the lower extremities, which accentuated on the left side combined with urinary incontinence and anal sphincter dysfunction but without sensory deficits of the lower extremities.[ncbi.nlm.nih.gov]
Hematuria
  • However, it has been associated with uncommon comorbidities such as painless gross hematuria secondary to renal papillary necrosis and renal medullary carcinoma.[ncbi.nlm.nih.gov]
  • We describe the case of a 27-year-old woman with a history of sickle cell trait (SCT) who presented with several months of hematuria and was found to have nutcracker syndrome (NCS).[ncbi.nlm.nih.gov]
  • Hematuria should prompt immediate investigation.[ncbi.nlm.nih.gov]
  • Two main causes of hematuria are papillary necrosis and renal RMC. 9 Vascular abnormalities that cause hematuria also lead to the impairment of urinary concentration and even isosthenuria.[touchoncology.com]
  • Tags: Anemia hematuria Hyposthenuria myth Neoplasm Renal Cancer Renal Papillary Necrosis Sickle Cell Sickle Cell Disease Sickle Cell Trait Splenic Infarct Sean M.[pedemmorsels.com]
Incontinence
  • A few hours after surgery, the patient developed an acute paraplegia of the lower extremities, which accentuated on the left side combined with urinary incontinence and anal sphincter dysfunction but without sensory deficits of the lower extremities.[ncbi.nlm.nih.gov]

Workup

  • Blood peripheral smear: Positive sickle cell test
  • Hemoglobin analysis: Sickle cell trait is characterized by the presence of both normal adult hemoglobin A (HbA) and hemoglobin S (HbS) on electrophoresis, in the ratio Hb S/A:40/60. Agar gel electrophoresis and electrophoresis are the electrophoretic techniques used. A wide range of mutant hemoglobins can usually be characterized by more specialized techniques such as isoelectric focusing and/or high-pressure liquid chromatography (HPLC) [8].
  • Genetic tests: Complete characterization, including amino acid sequencing or gene cloning and sequencing may be done. Polymerase chain reaction (PCR), automated DNA sequencing and allele-specific oligonucleotide hybridization allow identification of globin gene mutations in a few days. Genetic counselling after a genotyping is necessary.
ST Elevation
  • Electrocardiogram and cardiac enzymes confirmed acute ST elevation MI. Laboratory tests indicated hyperlipidemia and elevated liver enzyme levels 4 times the upper normal limit (UNL).[ncbi.nlm.nih.gov]

Treatment

Patients with sickle cell trait are symptomless and require no treatment. They are recommended to maintain oral hydration during or in anticipation of periods of extreme physical exertion, exposure to heat or cold, emotional stress, or infection. Travel in an unpressurized cabin and high altitudes may cause sickle cell crisis.

Prognosis

Individuals with sickle cell trait have normal life expectancy and no anemia. They are not at excessive risk for infection and not prone to develop painful crisis under normal circumstances. If factors predisposing to sudden death or sickle cell crisis are avoided, the person has a normal life like the general population [5].

Etiology

Sickle cell trait is an inherited condition. It is one of the sickle cell disorders, in which the homozygous (SS) sickle cell disease and many other forms of hemoglobinopathies are included. Sickle cell trait is an heterozygous carrier state which is inherited in autosomal recessive form, resulting in the occurence of a HbS gene [2].

Epidemiology

In the United States, the prevalence of sickle cell trait is approximately 8 to 10% in African Americans. The group of sickle cell diseases constitutes the most common severe genetic disease in the UK and France. HbS gene is widespread throughout the world, with significant presence in Africa, Mediterranean countries, the Middle East, and parts of India. The prevalence of sickle cell trait is the highest at 25 to 30% in certain areas of western Africa. The Hispanic population in the Unites States has sickle cell trait in 1 in 180 live births. There are approximately 2.5 million people in the United States and 300 million in the world who have sickle cell trait. The presence of sickle cell trait confers some protection against severe falciparum malaria, leading to the prevalence of this gene in malaria prone areas [3].

Sex distribution
Age distribution

Pathophysiology

Sickle cell hemoglobin results from a mutation in which the 17th nucleotide of the beta globin gene is changed from thymine to adenine and as a result the amino acid glutamic acid is replaced by valine at position 6 in the beta globin chain. Sickle cells have a reduced deformability and an increased fragility, causing respectively, occlusion of the microcirculation and anemia. HbS forms polymers under deoxy conditions and exhibits changes in solubility (gel formation) and molecular stability. The presence of normal adult hemoglobin has an inhibitory effect on gelation. Therefore, the presence of one normal and one sickle allele (HbAS) in sickle cell trait leads to absence of symptoms [4].

Prevention

Sickle cell trait cannot be prevented because it is an inherited disease. However, passing on the gene to children can be prevented if an individual knows his hemoglobin profile. Health complications can be avoided by taking proper steps. Severe hypoxia, severe dehydration and severe physical exertion can induce sudden death. Therefore caution is advised for flying in unpressurised aircraft and visiting very high altitudes. Care must be exercised if the person undergoes general anesthesia. Exertional heat injury, painful sickling crisis, splenic infarction, and sudden death can be avoided by adequate hydration and avoidance of severe heat [9].

Summary

Sickle cell trait is achieved through heterozygous inheritance of hemoglobin S, in which an individual possesses hemoglobin A at approximately 60% and hemoglobin S at approximately 40%. These individuals are hematologically normal. Excessive exertion or severe hypoxia may precipitate sickle cell crisis or sudden death. Avoidance of risk factors like exposure to heat and avoidance of severe exertion are usually enough to prevent morbidity. Screening for sickle cell trait is useful to inform affected persons of health risks and to provide information that might affect an individual's reproductive decisions [1].

Patient Information

  • Definition: Sickle cell trait is a condition when a person has one gene for an abnormal hemoglobin called HbS. 
  • Cause: Sickle cell trait is caused by a mutation in the gene that codes for the protein of the hemoglobin, an important component of the red blood cells that are responsible for carrying oxygen. 
  • Symptoms: Usually the person with sickle cell trait leads a normal life. Rarely, there may be blood in urine, kidney dysfunction, infarction of the spleen, severe muscle damage and pain after exertion and exercise-related sudden death. Some conditions may put a sickle cell trait individual in jeopardy of having a sickle cell crisis episode, such as air travel in an unpressurized cabin and high altitudes. Sickle cell crisis will cause symptoms of sudden moderate to severe pain in your back, knees, legs, arms, chest or stomach. 
  • Diagnosis: Blood test can diagnose sickle cell trait by detecting the presence of abnormal hemoglobin. Sometimes genetic testing may be required. 
  • Treatment and follow-up : Sickle cell trait does not require any treatment as such, but genetic counseling may be required if you are pregnant or want to start a family, as the sickle cell gene can be inherited by a child, and in case of the partner having sickle cell trait as well, can lead to sickle cell disease in the child. Adequate hydration must be maintained during exercise or sports. Exposure to excessive heat must be avoided, and resting intermittently during sporting activities is important [10]. 

References

Article

  1. Sears DA. The morbidity of sickle cell trait: a review of the literature. Am J Med 1978; 64:1021.
  2. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med 1997; 337:762.
  3. Ojodu J, Hulihan MM, Pope SN, Grant AM. Incidence of sickle cell trait--United States, 2010. MMWR Morb Mortal Wkly Rep. 2014; 63(49):1155-8.
  4. Steinberg MH, Forget BG, Higgs DR, et al. Disorders of hemoglobin: genetics, pathophysiology and clinical management. Cambridge University Press; Cambridge, UK: 2001.
  5. Tsaras G, Owusu-ansah A, Boateng FO, Amoateng-adjepong Y. Complications associated with sickle cell trait: a brief narrative review. Am J Med. 2009;122(6):507-12.
  6. Bucknor MD, Goo JS, Coppolino ML. The risk of potential thromboembolic, renal and cardiac complications of sickle cell trait. Hemoglobin 2014; 38:28.
  7. Kerle KK, Nishimura KD. Exertional collapse and sudden death associated with sickle cell trait. Am Fam Physician. 1996;54(1):237-40.
  8. Mousa SA, Qari MH. Diagnosis and management of sickle cell disorders. Methods Mol Biol. 2010;663:291-307.
  9. De montalembert M. Management of sickle cell disease. BMJ. 2008; 337:a1397.
  10. Scheinin L, Wetli CV. Sudden death and sickle cell trait: medicolegal considerations and implications. Am J Forensic Med Pathol. 2009;30(2):204-8.

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Last updated: 2018-06-22 07:22