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Anemia, Sickle Cell: Differential Diagnoses & Workup

Author: Ali Taher, MD, Professor of Medicine, Division of Hematology and Oncology, Assistant to the Chair-Undergraduate Program, Department of Internal Medicine, American University of Beirut Medical Center
Coauthor(s): Adlette Inati Khoriaty, MD, Head, Division of Pediatric Hematology-Oncology, Medical Director, Children's Center for Cancer and Blood Diseases, Rafik Hariri University Hospital; Research Associate, Balamand University; Head of Post Bone Marrow Transplant Clinic and Consultant Hematologist, Chronic Care Center, Lebanon; Ziad N Kazzi, MD, Assistant Professor, Department of Emergency Medicine, Emory University; Medical Toxicologist, Georgia Poison Center
Contributor Information and Disclosures

Updated: Dec 5, 2008

Differential Diagnoses

Acute Coronary Syndrome
Pneumonia, Bacterial
Anemia, Acute
Pneumonia, Empyema and Abscess
Anemia, Chronic
Pneumonia, Immunocompromised
Appendicitis, Acute
Pneumonia, Mycoplasma
Cholecystitis and Biliary Colic
Pneumonia, Viral
Gout and Pseudogout
Priapism
Hepatitis
Pulmonary Embolism
Meningitis
Rheumatic Fever
Osteomyelitis
Stroke, Ischemic
Pancreatitis
Subarachnoid Hemorrhage
Pelvic Inflammatory Disease
Urinary Tract Infection, Female
Pneumonia, Aspiration
Urinary Tract Infection, Male

Other Problems to Be Considered

Aplastic crisis
Septic arthritis
Chronic splenomegaly
Pulmonary infarction
Rib infarction
Sepsis
Splenic sequestration
Synovial thrombosis
Upper respiratory tract infection

Workup

Laboratory Studies

  • Assess hemoglobin and hematocrit levels. Anemia is often identified; however, a major drop in hemoglobin (ie, more than 2 g/dL) from previously recorded values indicates a hematological crisis. If the reticulocyte count is normal, splenic sequestration is the probable cause. If the reticulocyte count is low, an aplastic crisis is the probable cause. If the reticulocyte count is high, hyperhemolytic crises is the probable cause.
  • Obtain a leukocyte count. Leukocytosis is expected in all patients with sickle cell anemia. Major elevation in the WBC count (ie, >20,000 per mm3) with a left shift raises suspicion for infection. Leucopenia is suggestive of parvovirus infection.
  • The platelet count is often elevated. If low, consider of hypersplenism.
  • In a peripheral smear, sickle-shaped RBCs are found along with target cells and nucleated red cells. Concomitant microcytosis and basophilic stippling are seen in sickle beta-thalassemia. Presence of Howell-Jolly bodies indicates that the patient is asplenic.
  • Arterial blood gases (ABGs) may be obtained in patients who are in respiratory distress to supplement information provided by oxygen saturation monitoring. This will reflect the severity of pulmonary crisis. Serial ABGs are necessary to follow the response in pulmonary crisis.
  • Obtain liver function tests in patients with abdominal pain. An elevated baseline indirect bilirubin level may be normal because of chronic hemolysis.
  • Type and crossmatch in case transfusion is necessary.
  • Perform urinalysis if the patient has fever or signs of urinary tract infection (UTI). Patients with sickle cell anemia often have hematuria and isosthenuria. If signs of urinary tract infection are present, obtain a urine Gram stain and culture.
  • If the diagnosis of sickle cell anemia is uncertain, a sickling test will establish the presence of HbS gene. It will not, however, differentiate between individuals who are homozygous and those who are heterozygous.
  • Hemoglobin electrophoresis, though not immediately useful in the ED, differentiates individuals who are homozygous from those who are heterozygous. 
    • A homozygous patient will have hemoglobin SS (HbSS, 80-90%), hemoglobin F (HbF, 2-20%), and hemoglobin A2 (HbA2, 2-4%).
    • A carrier patient will have HbSS (35-40%) and hemoglobin A (HbA, 60-65%).
    • The test is not accurate in a patient who has recently received blood transfusions.
  • Secretory phospholipase A2 (sPLA2), an enzyme that cleaves fatty acids from triglycerides, is an accurate marker for identifying present or incipient acute chest syndrome in young patients with sickle cell pain crises . Its serum concentration increases before acute chest syndrome becomes clinically apparent, peaks at the clinical onset of acute chest syndrome, and declines during its resolution.

Imaging Studies

  • Chest radiography
    • Perform in patients with respiratory symptoms.
    • Radiographic findings may initially be normal in patients with acute chest syndrome.
  • Bone radiography
    • Perform in patients with localized bone tenderness.
    • Do not differentiate between osteomyelitis and bone infarction in the early stages. Radiographic signs of osteomyelitis may not appear for 8-10 days.
    • A view of the vertebral column shows typical fish-mouth appearance of vertebrae in patients with sickle cell anemia. This is due to expansion of the bone marrow.
  • Ultrasonography
    • Use in patients with abdominal pain to rule out cholecystitis, cholelithiasis, or an ectopic pregnancy and to measure spleen and liver size.
    • Assess liver and spleen size.
    • Cardiac echo should be performed for patients with dyspnea.
  • Head CT or MRI is used if signs and symptoms of stroke are present.
  • Bone scans can aid in early differentiation of bone infarction and osteomyelitis.

More on Anemia, Sickle Cell

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

  1. Steen RG, Emudianughe T, Hankins GM, et al. Brain imaging findings in pediatric patients with sickle cell disease. Radiology. Jul 2003;228(1):216-25. [Medline].

  2. Pollack CV. Emergencies in sickle cell disease. Emerg Med Clin North Am. May 1993;11(2):365-78. [Medline].

  3. Frenette PS, Atweh GF. Sickle cell disease: old discoveries, new concepts, and future promise. J Clin Invest. Apr 2007;117(4):850-8. [Medline].

  4. Chiang EY, Frenette PS. Sickle cell vaso-occlusion. Hematol Oncol Clin North Am. Oct 2005;19(5):771-84, v. [Medline].

  5. Telfer P, Coen P, Chakravorty S, et al. Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London. Haematologica. Jul 2007;92(7):905-12. [Medline].

  6. 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].

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

  8. 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].

  9. [Best Evidence] 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].

  10. Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. Sep 11 1997;337(11):762-9. [Medline].

  11. Eberst M. Hereditary hemolytic anemias. In: Tintinalli JE, Ruiz E, Krome RL, eds. Emergency medicine: A Comprehensive Study Guide. 4th ed. New York: McGraw-Hill; 1996:987-990.

  12. Ballas SK. Current issues in sickle cell pain and its management. Hematology Am Soc Hematol Educ Program. 2007;2007:97-105. [Medline].

  13. Ballas SK. Pain management of sickle cell disease. Hematol Oncol Clin North Am. Oct 2005;19(5):785-802, v. [Medline].

  14. Bergeron MF, Cannon JG, Hall EL. Erythrocyte sickling during exercise and thermal stress. Clin J Sport Med. Nov 2004;14(6):354-6. [Medline].

  15. Boyd JH, Macklin EA, Strunk RC, et al. Asthma is associated with increased mortality in individuals with sickle cell anemia. Haematologica. Aug 2007;92(8):1115-8. [Medline].

  16. Buchanan ID, Woodward M, Reed GW. Opioid selection during sickle cell pain crisis and its impact on the development of acute chest syndrome. Pediatr Blood Cancer. Oct 15 2005;45(5):716-24. [Medline].

  17. 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].

  18. Givens M, Rutherford C, Joshi G, et al. Impact of an emergency department pain management protocol on the pattern of visits by patients with sickle cell disease. J Emerg Med. Apr 2007;32(3):239-43. [Medline].

  19. 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].

  20. Halasa NB, Shankar SM, Talbot TR, et al. Incidence of invasive pneumococcal disease among individuals with sickle cell disease before and after the introduction of the pneumococcal conjugate vaccine. Clin Infect Dis. Jun 1 2007;44(11):1428-33. [Medline].

  21. Inati A, Jradi O, Tarabay H, et al. Sickle cell disease: the Lebanese experience. Int J Lab Hematol. Dec 2007;29(6):399-408. [Medline].

  22. Ingram VM. Gene mutations in human haemoglobin: the chemical difference between normal and sickle cell haemoglobin. Nature. Aug 17 1957;180(4581):326-8. [Medline].

  23. Kato GJ, Gladwin MT. Hemolysis-associated pulmonary hypertension in sickle cell disease and thalassemia. Hematol J. 2007.

  24. 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].

  25. Morris CR, Kato GJ, Poljakovic M, et al. Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease. JAMA. Jul 6 2005;294(1):81-90. [Medline].

  26. 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].

  27. Okpala I. The management of crisis in sickle cell disease. Eur J Haematol. Jan 1998;60(1):1-6. [Medline].

  28. Pauling L, Itano HA. Sickle cell anemia a molecular disease. Science. Nov 25 1949;110(2865):543-8. [Medline].

  29. Sears DA. The morbidity of sickle cell trait: a review of the literature. Am J Med. Jun 1978;64(6):1021-36. [Medline].

  30. Serjeant GR. Natural history and determinants of clinical severity of sickle cell disease. Curr Opin Hematol. Mar 1995;2(2):103-8. [Medline].

  31. Steinberg MH. Management of sickle cell disease. N Engl J Med. Apr 1 1999;340(13):1021-30. [Medline].

  32. Steinberg MH, Barton F, Castro O, et al. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. Apr 2 2003;289(13):1645-51. [Medline].

  33. Stephens CR. Sickle cell disease: a review of state-of-the-art emergency management and outcome-effective therapy. Emerg Med Rep. 1999;20:183-192.

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

  35. Styles LA, Aarsman AJ, Vichinsky EP, et al. Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease. Blood. Nov 1 2000;96(9):3276-8. [Medline].

  36. Vichinsky E. Sickle cell disease. In: Schwarz GR, Cayton CG, et al, eds. Principles and Practice of Emergency Medicine. Vol 2. 3rd ed. Philadelphia: Lea & Febiger; 1992:2019-2024.

  37. Vichinsky EP. Current issues with blood transfusions in sickle cell disease. Semin Hematol. Jan 2001;38(1 Suppl 1):14-22. [Medline].

  38. Vichinsky EP, Neumayr LD, Earles AN, et al. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. Jun 22 2000;342(25):1855-65. [Medline].

  39. Vichinsky EP, Styles LA, Colangelo LH, et al. Acute chest syndrome in sickle cell disease: clinical presentation and course. Cooperative Study of Sickle Cell Disease. Blood. Mar 1 1997;89(5):1787-92. [Medline].

  40. Wirthwein DP, Spotswood SD, Barnard JJ, et al. Death due to microvascular occlusion in sickle-cell trait following physical exertion. J Forensic Sci. Mar 2001;46(2):399-401. [Medline].

  41. Zurcher R. Sickle cell anemia. In: Hamilton GC, ed. Presenting Signs and Symptoms in the Emergency Department. Philadelphia, Pa: Lippincott Williams & Wilkins; 1993:328-336.

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Further Reading

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Keywords

sickle cell disease, sickle cell anemia, blood disorder, crescent cell anemia, sickle cell autosomal recessive genetic disease, hemoglobin S, HbS,  vasoocclusive crisis, avascular necrosis,  isosthenuria, acute chest syndrome, hypertransfusion programs, hematologic crises, aplastic crisis, parvovirus B19 infection, infectious crises, acute sequestration crisis, syncope

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Contributor Information and Disclosures

Author

Ali Taher, MD, Professor of Medicine, Division of Hematology and Oncology, Assistant to the Chair-Undergraduate Program, Department of Internal Medicine, American University of Beirut Medical Center
Disclosure: Nothing to disclose.

Coauthor(s)

Adlette Inati Khoriaty, MD, Head, Division of Pediatric Hematology-Oncology, Medical Director, Children's Center for Cancer and Blood Diseases, Rafik Hariri University Hospital; Research Associate, Balamand University; Head of Post Bone Marrow Transplant Clinic and Consultant Hematologist, Chronic Care Center, Lebanon
Adlette Inati Khoriaty, MD is a member of the following medical societies: Alpha Omega Alpha, American Society of Hematology, European Hematology Association, and International Society of Hematology
Disclosure: Nothing to disclose.

Ziad N Kazzi, MD, Assistant Professor, Department of Emergency Medicine, Emory University; Medical Toxicologist, Georgia Poison Center
Ziad N Kazzi, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College of Emergency Physicians, and American College of Medical Toxicology
Disclosure: Nothing to disclose.

Medical Editor

Roy Alson, MD, PhD, FACEP, FAAEM, Associate Professor, Department of Emergency Medicine, Wake Forest University School of Medicine; Medical Director, Forsyth County EMS; Deputy Medical Advisor, North Carolina Office of EMS; Associate Medical Director, North Carolina Baptist AirCare
Roy Alson, MD, PhD, FACEP, FAAEM is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, North Carolina Medical Society, Society for Academic Emergency Medicine, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School
Jonathan Adler, MD is a member of the following medical societies: American Academy of Emergency Medicine and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

 
 
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