Sickle Cell Trait - Essay Example

Sickle Cell Trait Sickle cell trait (SCT) is not a disease in itself. It refers to a condition in which a person inherits one normal gene for hemoglobin (A) from one parent and one abnormal gene for hemoglobin (S) from the other parent resulting in the genetic type (AS). One in 12 African – Americans and 1 in 100 Hispanic –Americans has sickle cell trait (CDC 2007). It also occurs in people who originate from the Middle East, India, and Eastern Mediterranean areas. The complications associated with this trait are mild and minimal and also people with this trait are as healthy as individuals who do not have this trait, but it assumes significance because children can inherit the sickle cell gene. Normal red blood cells are smooth and round and therefore can easily move through blood vessels. Sickle cell trait (AS) differs from sickle cell disease (SS) in which two abnormal hemoglobin genes is present, one from each parent. Sickle cell disease is a genetic disorder that affects red blood cells, making them rigid, sticky and sickle shaped. Sickling causes plugging of blood vessels to occur which essentially hinders the transport of oxygen from lungs to various organs in the body. The objective of this paper is to highlight the various aspects of the sickle cell trait namely the historical evidences, mode of inheritance and its various complications. Historical evidences: The first case of death due to sickle cell trait was documented between March 1968 and February 1969 at Fort Bliss where four army recruits collapsed and died during basic training. Since 2000, nine college football players have died from sickle cell trait complications, by far the biggest non-traumatic killer in the sport. In March 2008, a jury finds the UCF Athletics Association negligent in the death of 19-year old Erech Plancher, who collapsed and died after offseason conditioning drills. The jury awarded his parents $10 million in damages which is believed to be the largest payout in a wrongful-death case linked to sickle cell trait (Limon 2011). Mode of inheritance: Sickle cell disease is an autosomal recessive disease. When one parent has the sickle cell trait and the other has normal hemoglobin, their child has a 50% chance of having the trait (hemoglobin AS) and 50% chance of having normal (hemoglobin AA). When both parents have the trait, their child will have a 50% chance of having the trait (hemoglobin AS), as well as a 25% chance of being normal (hemoglobin AA) and a 25% chance of having sickle cell disease (hemoglobin SS). These risks are associated with each pregnancy. Linus Pauling asserts "I have suggested that the time might come in the future when information about heterozygosity in such serious genes as the sickle cell anemia gene would be tattooed on the forehead of the carriers, so that young men and women would at once be warned not to fall in love with each other." Complications: Sickle cell trait is normally considered a harmless condition, but extreme physical activity can lead to complications that can be fatal. Complications from sickle cell trait are important because about three million people in the United States have this genotype, about 40 to 50 times the number with sickle cell disease. (Kark 2000). When the individual is at rest, their red blood cells are normal but rigorous exercise regimes induce sickling to occur and cause several problems. Such problems include increased urinary tract infection in women, gross hematuria, splenic infarction with altitude hypoxia or exercise, and life-threatening complications of exercise, exertional heat illness (exertional rhabdomyolysis, heat stroke, or renal failure) or idiopathic sudden death (Sears 1978; Serjeant 1992; Kark and Ward 1994 and Sears 1994). We will consider each of these problems in more detail. The frequency of urinary tract infection is higher in women with SCT than in racially matched controls, especially during pregnancy, when the frequency is about double (Pastore, Savitz and Thorp 1990). The presence of SCT in men was not associated with increased frequency of urinary tract infection in a large study of patients in U.S. Department of Veterans Affairs’ hospitals (Heller, Best, Nelson and Becktel 1979). Hematuria has been fairly well studied in multiple studies of individuals with SCD. However, the difference in susceptibility and frequency of hematuria in sickle cell trait is not well understood. In a study done in Atlanta on 40 patients with sickle cell trait hospitalized during a 14 month period, 7 (18 %) were admitted because of hematuria (Chapman, Reader, Friedman 1955). A Jamaican study noted unexplained hematuria requiring hospitalization only once in 10 years in 119 patients with sickle cell trait (Ramirez, Hartley, Rhodes 1976). The reasons could be attributed to the relatively hypertonic, hypoxic and acidotic conditions in the renal medulla which clearly show intravascular sickling. Once identified, affected individuals tend to have repeated episodes with no proven association of progression to renal insuffiency or end stage renal disease (Mitchell 2000). The hematuria is typically painless with at least one report describing a 4:1 increased frequency among males with the trait (Ashcroft 1976). Blunt trauma to the eye can cause bleeding in the front (or anterior chamber) of the eye between the cornea and the iris. This bleeding into the anterior chamber of the eye is called a hyphema. Secondary hemorrhage, increased intraocular pressure, central retinal artery occlusion, and optic nerve atrophy tend to complicate traumatic hyphema in patients with sickle cell trait (Hooper, Bell, Farinelli and Grigg 2006). The complications are often out of proportion to the size of the hyphema. Conditions in the aqueous humor are conducive to erythrocyte sickling. The sickled red blood cells block the trabecular meshwork, leading to increased intraocular pressure. This leads to further stagnation of blood in the microvasculature, excessive deoxygenation, and more sickling (Tsaras, Owusu-Ansah, Boateng and Adjepong 2009). Splenic infarction in sickle cell trait are more common in the setting of exposure to low oxygen tension at high altitudes, including flight in unpressurized aircraft cabins or exercise in mountainous areas in those not acclimatized to such areas (Franlin and Compeggie 2009; Cooley, Peterson, Engel and Jernigan 1954; Sheikha 2005). In normal cases, splenic infarcts are mild but in certain extreme cases it becomes characterized by severe abdominal pain, splenomegaly, and left upper quadrant tenderness. Increase in the levels of bilirubin, serum lactate dehydrogenase, reticulocytosis, and anemia may be seen. There is the possibility of splenic rupture to happen, necessitating emergency splenectomy. The spleens become enlarged due to clogging with sickled cells. Adequate hydration, analgesia, rest and oxygen can manage most cases of splenic infarction. Exercise-related deaths occur at higher rates in individuals with sickle cell trait (Mitchell 2007; Kark, Posey, Schumacher, Ruehle 1987; Drehner, Neuhauser, Neuhauser, Blackwood 1999).These deaths result from exercise-related rhabdomyolysis (the breakdown of skeletal muscle), heat stroke, acute renal failure, disseminated intravascular coagulation, and cardiac arrhythmia. This risk was originally discovered by scientists studying the deaths of four U.S. Armed Forces recruits during basic training at Fort Bliss. All four were found to have sickle cell trait and the most common causes of death were "exertional skeletal muscle and cardiopulmonary arrest due to high potassium levels (Reynolds 2011). About 50% of cases resulted from exertional heat illness and the remaining cases were idiopathic (arising spontaneously) sudden deaths (ISD). Clinical features and distribution of cases between EHI and ISD did not differ by the presence or absence of hemoglobin S, except that rhabdomyolysis was the predominant form of EHI among cases with sickle cell trait. (Kark and Ward 1994) Works Cited Ashcroft MT. Mortality and morbidity in Jamaican adults with sickle cell trait and with normal hemoglobin followed for 12 years. Lancet. 1976; 2:784. Centre for Disease Control and Prevention (CDC). Sickle Cell Disease, Web. N.p., 14 December 2007. Chapman AZ, Reader PS, Friedman IA, et al: Gross hematuria in sickle cell trait and sickle cell hemoglobin-C disease. Am J Med. 1955; 19:773. Cooley JC, Peterson WL, Engel CE, Jernigan JP. Clinical triad of massive splenic infarction, sicklemia trait, and high altitude flying. JAMA. 1954;154:111-113. Drehner D, Neuhauser KM, Neuhauser TS, Blackwood GV. Death among US Airforce basic trainees, 1956 to 1996. Mil Med. 1999; 164:841-847. Franlin QJ, Compeggie M. Splenic syndrome in sickle cell trait: four case presentations and a review of the literature. Mil Med. 1999;164:230-233. Heller P, Best, WR, Nelson RB, Becktel J. Clinical implications of sickle cell trait and glucose-6-phosphate dehydrogenase deficiency in hospitalized black male patients. N Engl J Med 1979; 300: 1001-5. Hooper CY, Fraser-Bell S, Farinelli A, Grigg JR. Complicated hyphema: think sickle. Clin. Experiment. Opthalmol. 2006; 34: 377-378. Kark JA, Posey DM, Schumacher HR, Ruehle CJ. Sickle cell trait as a risk factor for sudden death in physical training. N Engl J Med.1987;317:781-787. Kark, JA, Ward, FT. Exercise and hemoglobin, S. Semin Hematol 1994; 31, pp.181-225. Kark, John. Sickle cell trait. Harward university school of medicine, Washington D.C. 20December 2000. Limon, lliana. Timeline of important sickle cell trait dates, Orlando Sentinel, EDT, July 26 2011. Mitchell BL. Sickle cell trait and sudden death-bringing it home. J NatlMed Assoc. 2007;99:300-305. Mitchell, Bruce L. Morbidity Associated With Sickle Cell Trait. June, 2000, Jacksonville Medicine Pastore LM, Savitz DA, Thorp JM Jr. Predictors of urinary tract infection at the first prenatal visit. Epidemiology. 1999; 10: PP. 282-7. Pauling, Linus. Letter to S. Leona rd Wadler. August 15, 1966. Ramirez A, Hartley LH, Rhodes D, et al. Morphological features of red blood cells in subjects with sickle cell trait: Changes during exercise. Arch Intern Med. 1976; 136:1064-1066. Reynolds, Denise. Exercise Therapy to Help Sickle Cell. Web, n.p. 14 June 2011 Sears, DA The morbidity of sickle cell trait: a review of the literature. Am J Med. 1978; 64: pp. 1021-36. Sears, DA. Sickle Cell trait. In: Embury SH, Hebbel RP, Mohandas N, Steinberg MH, eds. Sickle cell disease: basic principles and clinical practice. New York, Raven Press, 1994: pp.381-94. Serjeant, GR: The sickle cell trait. In: Serjeant GR, ed., Sickle cell disease. Second edition, New York City, Oxford University Press, 1992: pp. 415-25. Sheikha A. Splenic syndrome in patients at high altitude with unrecognized sickle cell trait: splenectomy is often unnecessary. Can J Surg.2005;48:377-381. Tsaras, Geoffrey, Owusu-Ansah Amma, Boateng Freda Owusua, Amoateng-Adjepong, Yaw. Complications Associated with Sickle Cell Trait: A Brief Narrative Review The American Journal of Medicine (2009) 122, 507-512 Summary Sickle cell trait (SCT) is not a disease and it occurs when a person inherits one normal gene for hemoglobin (A) from one parent and one abnormal gene for hemoglobin (S) from the other parent resulting in the genetic type (AS) and it differs from sickle cell disease (SS) in which two abnormal hemoglobin genes is present, one from each parent. The red blood cells become sickle shaped and obstruct oxygen flow through blood vessels to the various organs in the body. The earliest case of SCD occurred at Fort Bliss where four army recruits died during basic training. Ever since, death of several footballers has been reported and the latest evidence is that of Erech Plancher, who collapsed and died after offseason conditioning drills. SCD t assumes significance because children can inherit the sickle cell gene. When one parent has the sickle cell trait and the other has normal hemoglobin, their child has a 50% chance of having the trait (hemoglobin AS) and 50% chance of being normal (hemoglobin AA). When both parents have the trait, their child will have a 50% chance of having the trait (hemoglobin AS), as well as a 25% chance of being normal (hemoglobin AA) and a 25% chance of having sickle cell disease (hemoglobin SS). Basically it is a harmless condition but extreme stress can lead to complications some of which may be fatal. Some of the complications associated with SCD are urinary tract infection in women, gross hematuria, splenic infarction with altitude hypoxia or exercise, and life-threatening complications of exercise, exertional heat illness or idiopathic sudden death. Paraphrase Sickle cell trait (SCT) is not a disease in itself and is a genetic condition in which a person inherits one normal gene for hemoglobin (A) from one parent and one abnormal gene for hemoglobin (S) from the other parent resulting in the genetic type (AS). It is common amongst the African Americans, Hispanic Americans and people from the Mediterranean, India and the Middle East. Individuals with this trait are healthy and lead normal lives but there is the danger of children inheriting the trait from their parents. Persons having sickle cell disease have two abnormal hemoglobin genes (SS), one from each parent, instead of one. Here the red blood cells that are normally round and smooth assume a sickle shape, which obstructs their movement through blood vessels and therefore hinders their most important function namely the transport of oxygen to the various body organs from the lungs. The goal of this paper is to highlight some of the aspects of SCT namely, the historical evidences, mode of inheritance and some of the associated complications. The first evidence of death due to SCT was reported between 1968 and 1969 at Fort Bliss, where four army recruits died. The years that followed also saw many deaths especially amongst footballers and the last case that was reported was that of Erech Plancher, a 19-year old, who died after offseason conditioning drills. His parents were however awarded $10 million in damages by the jury, the highest so far in a wrongful- death case. While looking at the pattern of inheritance in SCT, it is seen that when one parent has the trait and the other has normal hemoglobin, their child has half the chance of having the trait and half the chance of having normal hemoglobin. But when both parents have the trait, the child has half the chance of having the trait as well as a 25% chance of being normal and a 25% chance of having sickle cell disease and the risks are associated with each pregnancy. Though considered a harmless condition, there is a possibility of severe complications arising during strenuous physical workouts and activities. About three million people in the United States have the genotype which is roughly about 40 to 50 times the number with the disease. Some of the major complications associated with this trait are increased urinary tract infection in women, gross hematuria, splenic infarction with altitude hypoxia or exercise, and life-threatening complications of exercise, exertional heat illness (exertional rhabdomyolysis, heat stroke, or renal failure) or idiopathic sudden death. In women, especially during pregnancy, the frequency of urinary tract infection is found to double. A study conducted on patients in U.S. Department of Veterans Affairs’ hospitals showed that, in men, unlike in women, the presence of SCT had no association with increased frequency of urinary tract infection. Hematuria (presence of blood in the urine) is a condition whose association with sickle cell trait is not well understood. Out of the 40 patients with sickle cell trait during a 14 month hospitalization period in a study in a hospital in Atlanta, 7 were admitted because of hematuria. In Jamaica, in a study conducted on 119 patients with SCT, the reasons for hospitalization only once in 10 years due to hematuria could not be understood. The conditions in the renal medulla in patients with SCT could be hypertonic, hypoxic and acidic and this could lead to hematuria. Hematuria though painless is a recurring condition that is more common in males with SCT. Bl;eeding in the anterior chamber of the eye is called hyphema. The conditions that can complicate hyphema in poatients with SCT are increased intraocular pressure, central retinal artery occlusion, and optic nerve atrophy. The intraocular pressure increases due to sickling of red blood cells in the aqueous humor leading to greater deoxygenation and sickling. Splenic infarction is a condition that becomes pronounced in people with SCT who are not acclimatized to conditions of low oxygen tension at high altitudes, including flight in unpressurized aircraft cabins or exercise in mountainous areas. In extreme cases it can cause severe abdominal pain, enlargement of the spleen, increase in levels of bilirubin, serum LDH, reticulocytosis (an increase in number of reticulocytes, the immature red blood cells) and anaemia. Splenecctomy becomes a necessity in cases where there is a splenic rupture. This condition can be managed by hydration, adequate rest and oxygen and analgesia. The reasons for exercise-related deaths in persons with SCT were due to the breakdown of the skeletal muscle (a condition called rhabdomyolysis), acute renal failure, intravascular coagulation and abnormal electrical activity in the heart (commonly known as cardiac arrhythmia). This was previously discovered by scientists studying the deaths of four U.S. Armed Forces recruits during basic training at Fort Bliss. The most common reasons for death seen in these recruits having SCT were exertional skeletal muscle and cardiopulmonary arrest due to high potassium levels. About half of the deaths seen normally are due to exertional heat illness (EHI) and the remaining cases were idiopathic (arising spontaneously) sudden deaths (ISD). Nevertheless, rhabdomyolysis was the predominant form of EHI in the cases with SCT. Quote Linus Pauling asserts "I have suggested that the time might come in the future when information about heterozygosity in such serious genes as the sickle cell anemia gene would be tattooed on the forehead of the carriers, so that young men and women would at once be warned not to fall in love with each other." Read More