Hemoglobinopathies in Sport: Thalassemia, Sickle Cell Trait
Bernadette Pendergraph
Evan Bass
BasicsDescription
Thalassemia and sickle cell trait are genetic disorders of hemoglobin production. Thalassemias are a mixed collection of quantitative abnormal production, leading to either absent or decreased production of normal alpha or beta subunits. Sickle cell trait produces an abnormal beta subunit in normal amounts.
Epidemiology
Incidence
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Thalassemia: 1 in 1,000 people has thalassemia in the U.S.
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Sickle cell trait: 8–10% of American blacks and 0.05% of American whites; 1 in 3 persons in West Africa and 1 in 5 persons in the eastern province of Saudi Arabia have sickle cell trait (1).
Prevalence
Thalassemia is the most common single genetic disorder known. In the thalassemia belt (Mediterranean, Turkey, Iran, India, Thailand, Cambodia, and southern China), the prevalence is 2.5–15% (2); 2.5 million people in the U.S., and 300 million people worldwide have sickle cell trait (1).
Risk Factors
Genetics
The condition is caused by the inheritance of an autosomal-recessive gene.
General Prevention
Genetic screening and preconception counseling
Etiology
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Thalassemia occurs when there is an abnormal gene on chromosome 11 or 16 that impairs the production of alpha or beta subunits of hemoglobin. Abnormalities include point mutations, total deletions, or the rearrangement of gene loci. Thalassemia minor occurs when a single abnormal gene is inherited, resulting in normal or low-normal hemoglobin measurement with significant microcytosis. More severe forms of beta thalassemia impair erythropoietin production, cause hemolytic anemia, and reduce oxygen capacity (2).
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Sickle cell trait occurs from the inheritance of 1 normal hemoglobin gene (HbA) and 1 abnormal B1 globin gene (HbS). In this carrier state, hemoglobin A1 and hemoglobin S is produced in a 60:40 ratio. The B1 gene is found on the short arm of chromosome 11. RBCs will sickle and polymerize under certain conditions, such as severe tissue hypoxia, acidosis, dehydration, increased viscosity, and hypothermia (3).
Commonly Associated Conditions
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Sickle cell trait: Increased incidence of hyposthenuria, microhematuria, renal papillary necrosis, exertional rhabdomyolysis, exercise-related sudden death, and renal medullary carcinoma; 2-fold increase in venous thrombosis; splenic infarcts reported at high altitude (>7,000 feet) (1)
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Thalassemia minor is usually asymptomatic. Other forms of thalassemia are associated with erythroid hyperplasia (extramedullary erythropoietic tissue development in face, chest, abdomen, and pelvis), resulting in frontal bossing, coarse facies, and splenomegaly. Heart failure occurs secondary to hemolytic anemia. Other bone abnormalities include shortened upper extremities, pathological fractures of long bones and vertebral bodies, notching, and osteolytic lesions of the ribs because of marrow masses. Growth retardation, delayed pubertal development, insulin resistance, hypothyroidism, and hypoparathyroidism are also possible complications.
DiagnosisPre Hospital
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Sickle cell trait: Usually asymptomatic; may present with cramping or sudden collapse, usually within the 1st 30 min of intense practice and initial conditioning with normal core temperature.
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Thalassemia minor: Usually asymptomatic.
History
Sickle cell trait: Muscle cramps with exertion
Physical Exam
Sickle cell trait: Muscles are soft and nontender to palpation; no visible contractions.
Diagnostic Tests & Interpretation
Lab
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Hemoglobin electrophoresis: Sickle cell trait shows hemoglobin AS (hemoglobin A1, 55–60%, and hemoglobin S, 40–45%) (3,4).
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CBC: Sickle cell trait leads to microcytosis and hypochromia.
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Reticulocyte count: Normal in sickle cell trait but increased when combined with alpha or beta thalassemia.
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Indirect bilirubin: Normal in sickle cell trait but increased when combined with alpha or beta thalassemia.
Differential Diagnosis
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Alpha thalassemia:
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1 gene deletion
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Asymptomatic; normal hematologically
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Alpha thalassemia:
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2 gene deletion
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Microcytosis and mild anemia, not reversed with iron
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Beta minor thalassemia:
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1 normal gene and 1 abnormal
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Microcytosis and mild anemia not reversed with iron
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Sickle cell trait combined with beta minor thalassemia or alpha thalassemia:
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Usually symptomatic
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Sickle cell trait combined with hemoglobin C
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Iron deficiency anemia:
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Microcytosis, decreased iron stores; improves with iron repletion
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Dilutional pseudoanemia:
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Increased volume expansion related to exercise; normal RBC indices and iron stores
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P.303
Treatment-
No treatment for asymptomatic sickle cell trait; focus is on prevention of exertional rhabdomyolysis and exertional collapse
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Collapse in sickle cell athlete:
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Occurs from sickling of RBCs in exerting limbs, with resultant rhabdomyolysis from continued exertion in the face of ischemia.
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Severe lactic acidosis from anaerobic metabolism of ischemic muscles can develop, leading to eventual shock.
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Rapid diagnosis and treatment are necessary to prevent acute renal failure from the rhabdomyolysis, subsequent hyperkalemia, eventual ventricular fibrillation, and death.
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Pre-Hospital
Sickle cell trait: If cramping or collapse, check vital signs, administer high-flow oxygen, cool athlete if necessary, and activate emergency medical services if patient is obtunded or vital signs are unstable.
ED Treatment
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Continued support: Oxygen, IV fluids
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Evaluation for rhabdomyolysis: CBC, electrolytes, BUN, creatinine, liver function tests, coagulation panel
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Correction of hyperkalemia
Additional Treatment
General Measures
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Sickle cell trait:
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Education of the athlete on importance of conditioning and identification of cramping as a sign of sickling.
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All athletes with the sickle cell trait should be counseled on preseason strength and conditioning programs, gradual progression during session training, and stopping activity if cramping, difficulty catching breath, weakness, or pain.
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When performing repetitive sprints/interval training, longer periods should be allowed for athlete to recover in between exertional activities.
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Exertion should be limited when conditions exist that may precipitate sickling: Illness, high ambient temperature, dehydration, asthma, altitude (5)
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Thalassemia: In severe cases, transfusions to keep the hemoglobin 9–10.5 g/L; chelation therapy in those receiving transfusions with deferoxamine, deferasirox, or deferiprone
Referral
Hematology referral: Patients with symptomatic sickle cell trait; concern for misdiagnosis and need for more advanced testing
Ongoing CarePatient Education
Sickle Cell Disease Association of America: http://www.sicklecelldisease.org/about/scd/index.phtml
Information Center for Sickle Cell and Thalassemia Disorders: http://sickle.bwh.harvard.edu/
Prognosis
Excellent, if prevention measures are instituted.
References
1. Tsaras G, Owusu-Ansah A, Boateng FO, et al. Complications associated with sickle cell trait: a brief narrative review. Am J Med. 2009.
2. Giardina PJ, Forget BJ. Thalassemia syndromes. In Hoffman: Hematology: basic principles and practice, 5th ed. Churchill Livingstone, 2008:
3. Hebbel RP. Variant sickle cell syndromes. In Hoffman: Hematology: basic principles and practice, 5th ed. Churchill Livingstone, 2008.
4. www.scinfo.org/sicklecelltrait.htm accessed October 12, 2009
5. NATA Consensus statement: sickle cell trait and the athlete. Accessed on 8/7/09 at http:/www.nata.org/statements/consensus/sicklecell.pdf
Additional Reading
Mercer KW, Densmore JJ. Hematologic disorders in the athlete. Clin Sports Med. 2005;24:599–621.
CodesICD9
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282.41 Sickle-cell thalassemia without crisis
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282.42 Sickle-cell thalassemia with crisis
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282.49 Other thalassemia