MANAGEMENT OF SICKLE CELL DISEASE

NIH Publication No. 02-2117. 188 pages. Revised May28, 2002 (Forth Edition) National Institutes of Health, National Heart, Lung, and Blood Institute. Download the entire PDF  file for Adobe  Return  to table of contents

Chapter 3. Sickle Cell Trait

Individuals who have sickle cell trait (SCT) do not have vaso-occlusive symptoms under physiologic conditions and have a normal life expectancy. The inheritance of SCT should have no impact on career choices or lifestyle. SCT is found in 8 percent of African Americans and is also prevalent in persons of Mediterranean, Middle Eastern, Indian, Caribbean, and Central and South American descent. Neonatal screening (chapter 2) will provide early detection of SCT. This chapter will discuss clinical syndromes associated with SCT, some of which occur only under conditions of extreme physiologic stress.

The presence of SCT significantly alters the management of traumatic hyphema, which is discussed more fully in chapter 14, Sickle Cell Eye Disease.

RENAL AND GENITOURINARY TRACT

Individuals with SCT can develop microscopic infarction of the renal medulla, resulting in loss  of maximal urine concentrating ability; this condition is present in most adults with SCT (1). Maximum urine osmolality following fluid  deprivation or intranasal DDAVP may be as low as 400 to 500 mOsm/kg. Coexistent a-thalassemia provides partial protectionagainst this urine-concentrating defect (2).

(ALSO SEE CHAPTER 19, RENAL ABNORMALITIES IN SICKLE CELL DISEASE)

Necrosis of the renal papillae can result in hematuria, which is usually microscopic. Gross hematuria is occasionally provoked by heavy exercise or occurs spontaneously. Individuals with hematuria should be evaluated by a urologist, who will perform imaging studies as needed to exclude neoplasms (3-5) or renal stones or any related problems with flow of urine from the calyces to the urethra.

Individuals with acute episodes of gross hematuria are cautioned to avoid exercise but are encouraged to continue to perform sedentary work. They are encouraged to take fluids (equivalent to half-normal saline) and may also receive sodium bicarbonate 650 to 1,200 mg per day. If bleeding persists, an antifibrinolytic agent such as epsilon aminocaproic acid (EACA) can be prescribed (6). In a controlled trial of individuals with SCT who had hematuria, administration of EACA at an oraldose of 6 to 8 grams daily in four to six divided doses caused resolution of hematuria at a mean of 2.2±0.3 days, compared with 4.5±1.9 days for those individuals not receiving the  drug (6). The authors reported a high incidence of ureteral obstruction by clots accompanied by flank pain (in 15 of 38 episodes with an intravenous pyelogram [IVP]), which resolved without specific therapy over 2 to 37 days. However, ureteral obstruction by clot also occurred at the same frequency in the absence of EACA. Although the best dose and duration for use of EACA in treatment of hematuria related to SCT has not been adequatelyinvestigated, one effective regimen is administration of 3 grams 3 or 4 times per day for1 week; in most patients, hematuria will resolve after 2 to 3 days (7). In some individuals, iron replacement and even transfusions may be required.

Occasionally, bleeding is so brisk or persistent that it is necessary to perform invasive surgery to visualize bleeding sites, identify the pathology at those sites, and stop the bleeding by local measures in order to save the kidney.

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 (8). The presence of SCT in men was not associatedwith increased frequency of urinary tract infection in a large study of patients in U.S. Department of Veterans Affairs’ hospitals (9).

AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

The incidence of end-stage renal failure from this disorder is identical for Caucasians and African Americans; however, the onset of end-stage renal failure occurs at an earlier age for individuals with SCT than for African Americans without SCT (38 years versus 48 years [p<0.003]) (10).

COMPLICATIONS OF STRENUOUS EXERCISE

Risk factors for exercise-related death of young adults with SCT include environmental heatstress during the preceding 24 hours (11), incomplete heat acclimation, wearing heat retaining clothing, dehydration, delay in recognition or treatment of exertional heat illness, obesity with poor exercise fitness (12), sustained heroic effort above customary activity, and inadequate sleep. Many of these factors were present in military recruits under extreme conditions of 8 weeks of physical training, where the excess mortality rate for those with SCT was 1 per 3300 in the late 1970’s (13).

The higher risk of exercise-related death is attributed mainly to the intensity of new exercises or to sustained duration for which the individual is unprepared. This higher risk is eliminated by measures to prevent exertional heat illness. SCT does not contraindicate participation in competitive sports. In fact, many reports show no increased morbidity or mortality for professional athletes with the trait (1) who stay fit during the off-season. Prevention of exertional heat illness requires hydration or similar measures for distance runners and military recruits (1,14,15). Individuals should increase performance levels gradually, and training should cease and restart slowly if myalgia occurs.

There is no requirement to screen for SCT before participation in athletic programs.

Splenic infarction usually presents as severe abdominal pain localized within a few hours to the left upper quadrant. It is best seen on a computerized tomography (CT) scan, which may show a region of hemorrhage. An episode of splenic infarction with SCT usually resolves in 10 to 21 days and rarely requires surgical  intervention. Splenic infarction associated with SCT may occur with hypoxemia from systemic disease or from exercise at sea level or at high altitude (1). Splenic infarction is associated with flights in unpressurized aircraft at 15,000 feet or more but may occur rarely at mountain altitudes higher than 6,000 feet above sea level. The frequency seems to be disproportionately greater in phenotypically non-African-American individuals (16), an observation that may be due to reporting bias. Nevertheless, numerous individuals with SCT have participated successfully in long-distance races in the Cameroon and in high-altitude sports, including the Olympics in Mexico City. Thus, the majority of people with SCT can travel safely to mountain altitudes for recreational activities; however, rare individuals who have had splenic complications may risk recurrence.

SURGERY AND OTHER MEDICAL CONDITIONS

Surgery is not likely to be complicated by the fact that an individual has SCT (17). Individuals with SCT are not at increased risk for an adverse outcome from anesthesia, and they are not limited in their choice of anesthetic agents. There is no convincing evidence that SCT is associated with increased frequency or severity of diabetic retinopathy, stroke, myocardial infarction, leg ulcers, avascular necrosis and arthritis, or the bends due to diving. Some case reports of possible associations of SCT with increased medical morbidity may represent situations in which other variants of - or a-globin chains produced undiagnosed SCD (18). Rare cases may be due to increased 2,3-DPG or altered oxygen affinity, which might increase polymerization of Hb S sufficiently to cause a phenotype of SCT to behave like SCD (18,19).

EDUCATION AND GENETIC COUNSELING

All persons with SCT should be educated about the inheritance of SCD and about the availability of partner testing, genetic counseling, and prenatal diagnosis (see chapter 4).

1. Kark JA, Ward FT. Exercise and hemoglobin S. Semin Hematol 1994;31:181-225.

2. Gupta AK, Kirshner KA, Nicholson R, et al. Effects of alpha-thalassemia and sickle polymerization tendency on the urineconcentrating defect of individuals with SCT. J Clin Invest 1991;88:1963-8.

3. Davis CJ Jr, Mostofi FK, Sesterhenn IA. Renal medullary carcinoma. The seventh sickle cell nephropathy. Am J Surg Pathol 1995;19:1-11.

4. Avery RA, Harris JE, Davis CJ Jr, et al. Renal medullary carcinoma: Clinical and therapeutic aspects of a newly described tumor. Cancer 1996;78:128-32.

5. Baron BW, Mick R, Baron JM. Hematuria in sickle cell anemia—not always benign: Evidence for excess frequency of sickle cell anemia in African Americans with renal cell carcinoma. Acta Haematol 1994;92:119-22.

6. Black WD, Hatch FE, Acchiardo S. Aminocaproic acid in prolonged hematuria of patients with sicklemia. Arch Intern Med 1976;136:678-81.

7. McInnes BK III. The management of hematuria associated with sickle hemoglobinopathies. J Urol 1980;124:171-4.

8. Pastore LM, Savitz DA, Thorp, JM Jr. Predictors of urinary tract infection at the first prenatal visit. Epidemiology 1999;10:282-7.

9. Heller P, Best WR, Nelson RB, et al. 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.

10. Yium J, Gabow P, Johnson A, et al. Autosomal dominant polycystic kidney disease in blacks: Clinical course and effects of sickle-cell hemoglobin. J Am Soc Nephrol 1994;4:1670-4.

11. Kark JA, Burr PQ, Wenger CB, et al. Exertional heat illness in Marine Corps recruit training. Aviat Space Environ Med 1996;67:354-60.

12. Gardner JW, Kark JA, Karnei K, et al. Risk factors predicting exertional heat illness in male Marine Corps recruits. Med Sci Sports Exerc 1996;28:939-44.

13. 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; 317:781-7.

14. Armstrong LE, Epstein Y, Greenleaf JE, et al. American College of Sports Medicine. Heat and cold illnesses during distance running: American College of Sports Medicine Position Stand. Med Sci Sports Exerc 1996;28:(12):i-x.

15. Montain SJ, Latzka WA, Sawka MN. Fluid replacement recommendations for training in hot weather. Mil Medicine 1999;164:502-8.

16. Lane PA, Githens JH. Splenic syndrome at mountain altitudes and SCT: Its occurrence in non-black persons. JAMA 1985;253:2251-4.

17. Steinberg MH. Sickle Cell Trait. In: Steinberg MH, Forget BG, Higgs DR, et al., eds. Disorders of Hemoglobin: Genetics, Pathophysiology and Clinical Management. Cambridge, UK: Cambridge University Press, 2001:811-30.

18. Witkowska E, Lubin B, Beuzard Y, et al. Sickle cell disease in a patient with SCT and compound heterozygosity for hemoglobin S and hemoglobin Quebec-Chori. N Engl J Med 1991;325:1150-4.

19. Cohen-Solal M, Prehu C, Wajcman H, et al. A new sickle cell disease phenotype associating Hb S trait, severe pyruvate kinase deficiency (PK Conakry), and an alpha2 globin gene variant (Hb Conakry). Br J Haematol 1998;103:950-6.

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Last modified: November 10, 2002