eMedicine Specialties > Pediatrics: General Medicine > Hematology

Sickle Cell Anemia: Differential Diagnoses & Workup

Author: Ashok B Raj, MD, Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children's Hospital, University of Louisville
Coauthor(s): Salvatore Bertolone, MD, Director, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Kosair Children's Hospital; Professor, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Jul 9, 2009

Differential Diagnoses

Other Problems to Be Considered

Hemoglobin (Hb)S– β -0 thalassemia
HbS– β plus thalassemia
HbSC disease

Workup

Laboratory Studies

  • Newborn hemoglobinopathy screening
    • The introduction of newborn screening is one of the greatest advances in the management of sickle cell disease. Currently, 49 states and the District of Columbia have mandatory universal programs for newborn screening for hemoglobin disorders. Guidelines for screening for sickle cell disease in newborns have been established.4 If results are positive, a repeat hemoglobin electrophoresis should be performed for confirmation.
    • Fetal hemoglobin is predominant in young infants.
    • If results show only hemoglobin (Hb) F and S, the child has either sickle cell anemia or HbS– β -0 thalassemia.
    • If results show Hb F, S, and C, the child has HbSC disease.
    • If results show Hb F, S, and A, determine whether the child has received a transfusion.
    • If the child has not received a transfusion and S is greater than A, HbS–beta plus thalassemia is most likely the diagnosis. If A is greater than S, the child is presumed to have the sickle trait. If A and S concentrations are close, conduct a study of the parents to determine if one of them has the thalassemia trait. Repeat Hb electrophoresis on the child after several months.
  • Normocytic hemolytic anemia
    • If results of electrophoresis show only HbS with a Hb F concentration of less than 30%, the diagnosis is sickle cell anemia.
    • If HbS and Hb C are present in roughly equal amounts, the diagnosis is HbSC disease.
  • Microcytic hemolytic anemia
    • If the child has microcytic hemolytic anemia, order quantitative Hb A2 in addition to electrophoresis.
    • If HbS is predominant, Hb F is less than 30% and Hb A2 is elevated, a diagnosis of HbS–beta-0 thalassemia can be inferred. If possible, perform a study of the parents.
    • If the Hb A2 level is normal, consider the possibility of concomitant HbSS and iron deficiency.
    • If HbS is greater than A and Hb A2 is elevated, a diagnosis of HbS–beta plus thalassemia can be inferred.
    • If HbS and Hb C are present in equal amounts, the diagnosis is HbSC disease.
  • Obtaining a series of baseline values on each patient to compare with those at times of acute illness is useful. The table below shows a typical schedule of routine clinical laboratory evaluations. Suggested routine clinical laboratory evaluations

    Open table in new window

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    Table
    TestsAgeFrequency
    CBC count with WBC differential,
    reticulocyte count    		3-24 mo
    >24 mo    		every 3 mo
    every 6 mo
    Percent Hh F6-24 mo
    >24 mo    		every 6 mo
    annually
    Renal function (creatinine, BUN, urinalysis)>12 moannually
    Hepatobiliary function (ALT, fractionated bilirubin)>12 moannually
    Pulmonary function (transcutaneous O2 saturation)>12 moevery 6 mo
    TestsAgeFrequency
    CBC count with WBC differential,
    reticulocyte count    		3-24 mo
    >24 mo    		every 3 mo
    every 6 mo
    Percent Hh F6-24 mo
    >24 mo    		every 6 mo
    annually
    Renal function (creatinine, BUN, urinalysis)>12 moannually
    Hepatobiliary function (ALT, fractionated bilirubin)>12 moannually
    Pulmonary function (transcutaneous O2 saturation)>12 moevery 6 mo

Imaging Studies

The brain and lungs are among the organs susceptible to serious damage in sickle cell disease. Early detection of dysfunction may allow intervention to reduce risk of further damage.

  • Brain
    • Transcranial Doppler ultrasonography (TCD), MRI with or without angiography, and neuropsychometric (NPM) studies have been used extensively to evaluate children with sickle cell disease. An abnormally high blood flow velocity determined with TCD in the middle cerebral or internal carotid arteries is associated with an increased risk of stroke; however, blood flow results should be interpreted cautiously because they depend on the technique used.
    • Physicians recommend beginning TCD screening of children with sickle cell disease at age 2 years and continuing annually if TCD results are normal or every 4 months if TCD results are marginal. Abnormal results should prompt a repeat TCD within 2-4 weeks. The Stroke Prevention in Sickle Cell Anemia (STOP) trial in 1997 demonstrated that a transfusion program reduces the risk of strokes in patients with abnormal TCD results.
    • Children with sickle cell disease who have "silent" cerebral infarcts revealed with MRI have a higher rate of abnormal NPM findings and a higher risk of overt strokes. Stroke prevention strategies based on abnormal MRI results have not been tested, but children with abnormal MRI or NPM findings may be evaluated more frequently and carefully and considered for therapeutic measures.
    • Newer techniques for noninvasive assessment of the brain have also been used to identify children with asymptomatic brain disease. Transcranial near infrared spectroscopy or cerebral oximetry is increasingly being used as a screening tool for low cerebral venous oxygen saturation in children with sickle cell disease.
  • Lungs: Children with sickle cell disease frequently have abnormal pulmonary function test (PFT) results. PFTs should be performed regularly in those with a history of recurrent acute chest episodes or low oxygen saturation. Because lung function declines with age, it is important to identify those who require close monitoring and treatment.
  • Heart: Echocardiography is used to identify patients with pulmonary hypertension based on tricuspid regurgitant jet velocity. Patients with sickle cell disease may have an array of abnormalities of systolic and diastolic function.
  • Abdominal ultrasonography: This can be used to visualize stones and to detect signs of thickening gall bladder walls or ductal inflammation, indicating possible cholecystitis.

More on Sickle Cell Anemia

Overview: Sickle Cell Anemia
Differential Diagnoses & Workup: Sickle Cell Anemia
Treatment & Medication: Sickle Cell Anemia
Follow-up: Sickle Cell Anemia
Multimedia: Sickle Cell Anemia
References
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References

  1. Heeney MM, Ware RE. Hydroxyurea for children with sickle cell disease. Pediatr Clin North Am. Apr 2008;55(2):483-501, x. [Medline].

  2. [Best Evidence] Strouse JJ, Lanzkron S, Beach MC, et al. Hydroxyurea for sickle cell disease: a systematic review for efficacy and toxicity in children. Pediatrics. Dec 2008;122(6):1332-42. [Medline].

  3. Adams RJ, McKie VC, Hsu L, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. N Engl J Med. Jul 2 1998;339(1):5-11. [Medline].

  4. [Guideline] US Preventive Services Task Force. Screening for sickle cell disease in newborns: U.S. Preventive Services Task Force recommendation statement. Agency for Healthcare Research and Quality (AHRQ). Sep 2007;[Full Text].

  5. Cappellini MD, Piga A. Current status in iron chelation in hemoglobinopathies. Curr Mol Med. Nov 2008;8(7):663-74. [Medline].

  6. Das BB, Sobczyk W, Bertolone S, Raj A. Cardiopulmonary stress testing in children with sickle cell disease who are on long-term erythrocytapheresis. J Pediatr Hematol Oncol. May 2008;30(5):373-7. [Medline].

  7. Adamkiewicz TV, Sarnaik S, Buchanan GR, et al. Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination. J Pediatr. Oct 2003;143(4):438-44. [Medline].

  8. Adams RJ, Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. Dec 29 2005;353(26):2769-78. [Medline].

  9. Boyd JH, Macklin EA, Strunk RC, DeBaun MR. Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood. Nov 1 2006;108(9):2923-7. [Medline].

  10. Brown AK, Sleeper LA, Miller ST, Pegelow CH, Gill FM, Waclawiw MA. Reference values and hematologic changes from birth to 5 years in patients with sickle cell disease. Cooperative Study of Sickle Cell Disease. Arch Pediatr Adolesc Med. Aug 1994;148(8):796-804. [Medline].

  11. Buchanan GR, DeBaun MR, Quinn CT, Steinberg MH. Sickle cell disease. Hematology Am Soc Hematol Educ Program. 2004;35-47. [Medline].

  12. Castro O, Brambilla DJ, Thorington B, et al. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood. Jul 15 1994;84(2):643-9. [Medline].

  13. Charache S, Terrin ML, Moore RD, et al. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med. May 18 1995;332(20):1317-22. [Medline].

  14. Gaston MH, Verter JI, Woods G, et al. Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. N Engl J Med. Jun 19 1986;314(25):1593-9. [Medline].

  15. Gill FM, Sleeper LA, Weiner SJ, et al. Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease. Blood. Jul 15 1995;86(2):776-83. [Medline].

  16. Gladwin MT, Sachdev V, Jison ML, et al. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. Feb 26 2004;350(9):886-95. [Medline].

  17. Hankins JS, Fortner GL, McCarville MB, Smeltzer MP, Wang WC, Li CS. The natural history of conditional transcranial Doppler flow velocities in children with sickle cell anaemia. Br J Haematol. Jul 2008;142(1):94-9. [Medline].

  18. Hankins JS, Ware RE, Rogers ZR, et al. Long-term hydroxyurea therapy for infants with sickle cell anemia: the HUSOFT extension study. Blood. Oct 1 2005;106(7):2269-75. [Medline].

  19. Hulbert ML, Scothorn DJ, Panepinto JA, Scott JP, Buchanan GR, Sarnaik S. Exchange blood transfusion compared with simple transfusion for first overt stroke is associated with a lower risk of subsequent stroke: a retrospective cohort study of 137 children with sickle cell anemia. J Pediatr. Nov 2006;149(5):710-2. [Medline].

  20. Kato GJ, Onyekwere OC, Gladwin MT. Pulmonary hypertension in sickle cell disease: relevance to children. Pediatr Hematol Oncol. Apr-May 2007;24(3):159-70. [Medline].

  21. Kaul DK, Liu XD, Zhang X, et al. Peptides based on alphaV-binding domains of erythrocyte ICAM-4 inhibit sickle red cell-endothelial interactions and vaso-occlusion in the microcirculation. Am J Physiol Cell Physiol. Nov 2006;291(5):C922-30. [Medline].

  22. Mantadakis E, Ewalt DH, Cavender JD, Rogers ZR, Buchanan GR. Outpatient penile aspiration and epinephrine irrigation for young patients with sickle cell anemia and prolonged priapism. Blood. Jan 1 2000;95(1):78-82. [Medline].

  23. Miller ST, Sleeper LA, Pegelow CH, et al. Prediction of adverse outcomes in children with sickle cell disease. N Engl J Med. Jan 13 2000;342(2):83-9. [Medline].

  24. Morris CR, Kato GJ, Poljakovic M, Wang X, Blackwelder WC, Sachdev V. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. Jul 6 2005;294(1):81-90. [Medline].

  25. Ohene-Frempong K, Weiner SJ, Sleeper LA, et al. Cerebrovascular accidents in sickle cell disease: rates and risk factors. Blood. Jan 1 1998;91(1):288-94. [Medline].

  26. Okpala I. Leukocyte adhesion and the pathophysiology of sickle cell disease. Curr Opin Hematol. Jan 2006;13(1):40-4. [Medline].

  27. Pegelow CH, Adams RJ, McKie V, et al. Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. J Pediatr. Jun 1995;126(6):896-9. [Medline].

  28. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. Jun 9 1994;330(23):1639-44. [Medline].

  29. Quinn CT, Buchanan GR. Sickle-cell anemia with unusual bone changes. J Pediatr. Sep 2003;143(3):350.

  30. Quinn CT, Rogers ZR, Buchanan GR. Survival of children with sickle cell disease. Blood. Jun 1 2004;103(11):4023-7. [Medline].

  31. Raj A, Bertolone S, Bond S, Burnett D, Denker A. Cathlink 20: a subcutaneous implanted central venous access device used in children with sickle cell disease on long-term erythrocytapheresis--a report of low complication rates. Pediatr Blood Cancer. Jun 15 2005;44(7):669-72. [Medline].

  32. Raj A, Bertolone S, Klapheke P, Burnett D, Suarez C. Impact of long-term erythrocytapheresis on splenic function in patients with sickle cell disease. J Pediatr Hematol Oncol. Oct 2002;24(7):545-7. [Medline].

  33. Raj A, Bertolone SJ, Mangold S, Edmonds HL Jr. Assessment of cerebral tissue oxygenation in patients with sickle cell disease: effect of transfusion therapy. J Pediatr Hematol Oncol. May 2004;26(5):279-83. [Medline].

  34. Raj AB, Condurache T, Bertolone S, Williams D, Lorenz D, Sobczyk W. Quantitative assessment of ventricular function in sickle cell disease: effect of long-term erythrocytapheresis. Pediatr Blood Cancer. Dec 2005;45(7):976-81. [Medline].

  35. Raj AB, O'brien LM, Bertolone SJ, Gozal D, Edmonds HL Jr. Cerebral oximetry improves detection of sickle cell patients at risk for nocturnal cerebral hypoxia. Pediatr Pulmonol. Nov 2006;41(11):1088-94. [Medline].

  36. Steinberg MH. Sickle cell anemia, the first molecular disease: overview of molecular etiology, pathophysiology, and therapeutic approaches. ScientificWorldJournal. Dec 25 2008;8:1295-324. [Medline].

  37. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. Oct 9-15 2004;364(9442):1343-60. [Medline].

  38. Uong EC, Boyd JH, DeBaun MR. Daytime pulse oximeter measurements do not predict incidence of pain and acute chest syndrome episodes in sickle cell anemia. J Pediatr. Nov 2006;149(5):707-9. [Medline].

  39. Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med. Jun 7 1990;322(23):1617-21. [Medline].

  40. Vichinsky EP, Haberkern CM, Neumayr L, et al. A comparison of conservative and aggressive transfusion regimens in the perioperative management of sickle cell disease. The Preoperative Transfusion in Sickle Cell Disease Study Group. N Engl J Med. Jul 27 1995;333(4):206-13. [Medline].

  41. Walters MC, Patience M, Leisenring W, et al. Bone marrow transplantation for sickle cell disease. N Engl J Med. Aug 8 1996;335(6):369-76. [Medline].

  42. Wang WC, Helms RW, Lynn HS, et al. Effect of hydroxyurea on growth in children with sickle cell anemia: results of the HUG-KIDS Study. J Pediatr. Feb 2002;140(2):225-9. [Medline].

  43. Zilberman MV, Du W, Das S, Sarnaik SA. Evaluation of left ventricular diastolic function in pediatric sickle cell disease patients. Am J Hematol. Jun 2007;82(6):433-8. [Medline].

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Further Reading

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Keywords

sickle cell anemia, sickle cell disease, crescent cell anemia, sickle-shaped erythrocytes, crescent-shaped erythrocytes, sickle cell crisis, ACS, acute chest syndrome, SCD, hemoglobin S, HbS, homozygotic HbSS, aplastic crisis, fifth disease, hemolytic anemia, Streptococcus pneumoniae, osteomyelitis, meningitis, acute chest syndrome, pulmonary infarction, respiratory distress, bone marrow infection, hand-foot syndrome, hypoxemia, dehydration, stroke, convulsion, priapism, bone marrow transplantation, hemorrhagic stroke, moya moya, cholecystitis, cholelithiasis, bile duct obstruction, unwanted erection, treatment, diagnosis

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Contributor Information and Disclosures

Author

Ashok B Raj, MD, Associate Professor, Section of Pediatric Hematology and Oncology, Department of Pediatrics, Kosair Children's Hospital, University of Louisville
Ashok B Raj, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Kentucky Medical Association
Disclosure: Nothing to disclose.

Coauthor(s)

Salvatore Bertolone, MD, Director, Division of Pediatric Hematology/Oncology, Department of Pediatrics, Kosair Children's Hospital; Professor, University of Louisville School of Medicine
Salvatore Bertolone, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Education, American Association of Blood Banks, American Cancer Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Kentucky Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Sharada A Sarnaik, MB, BS, Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Attending Hematologist/Oncologist, Children's Hospital of Michigan
Sharada A Sarnaik, MB, BS is a member of the following medical societies: American Association of Blood Banks, American Association of University Professors, American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

James L Harper, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center
James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society
Disclosure: Nothing to disclose.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine
Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

 
 
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