eMedicine Specialties > Pediatrics: General Medicine > Hematology

Evans Syndrome: Differential Diagnoses & Workup

Author: Prasad Mathew, MBBS, DCh, Director, Hemostasis and Hematology Program, Professor of Pediatrics, University of New Mexico
Contributor Information and Disclosures

Updated: Nov 19, 2009

Differential Diagnoses

Thrombocytopenia-Absent Radius Syndrome

Other Problems to Be Considered

Evans syndrome is a diagnosis of exclusion. Other causes of immune cytopenias should be excluded, such as:

SLE
IgA deficiency
Common variable immune deficiency
Acquired immune deficiency syndrome
Autoimmune lymphoproliferative syndrome
Paroxysmal nocturnal hemoglobinuria
Thrombotic thrombocytopenic purpura
Hemolytic-uremic syndrome
Kasabach-Merritt syndrome
Hypersplenism
Rosai Dorfman Disease (may be associated with autoimmune lymphoproliferative syndrome)

Workup

Laboratory Studies

  • The CBC count and reticulocyte count reveal anemia, thrombocytopenia, neutropenia, or combined cytopenias in patients with Evans syndrome; the reticulocyte count increases if the patient has anemia. Features of hemolysis include a raised reticulocyte count, increase in unconjugated bilirubin, and decreased haptoglobins.
  • In Evans syndrome, the direct antiglobulin result (ie, Coombs test result) is almost invariably positive (often weakly) and may be positive for IgG, complement, or both. Indirect antiglobulin test findings may also be positive in 52-83% of patients.
  • Prudent studies include measurement of serum immunoglobulins to rule out such differential diagnoses as common variable immunodeficiency and IgA deficiency; serum markers for conditions such as systemic lupus erythematosus (SLE), measuring antinuclear antibody, double-stranded DNA; and peripheral blood T-cell subsets using flow cytometry to rule out autoimmune lymphoproliferative syndrome and bone marrow examination to rule out infiltrative disorders.
  • Various antibodies directed against RBCs and platelets (eg, antierythrocyte, antineutrophil, antiplatelet antibodies) occur in association with Evans syndrome.
    • In a study by Fagiolo of 32 adults, as many as 91% had antiplatelet antibodies demonstrated using thromboagglutination and indirect antiglobulin consumption tests.16 About 81% had leukocyte antibodies detected using cytotoxicity testing. However, variable intervals were reported between the detection of antibodies and the demonstration of leukopenia or thrombocytopenia. No relationship was shown between the leukocyte antibodies and platelet antibodies (alone or in combination) and the type of RBC antibodies.
    • Kakaiya et al reported that the antibodies directed against RBCs and platelets were different.17 Pegels et al confirmed this finding.18 In absorption and elution experiments, they found that the autoantibodies were directed against specific antigens on RBCs, platelets, and white cells, and that the autoantibodies did not cross-react. These findings lead to questions about the clinical usefulness of these tests. Pui et al found platelet antibodies in only 2 of 6 children tested.7 Antineutrophil antibodies were positive in 3 of 4 patients with neutropenia. Therefore, positive antibody results are useful, but negative results provide little clinical information.

Other Tests

  • Lupus antibody (Lupuslike inhibitor) and antinuclear antibody tests are used to detect SLE.
  • Perform T-cell and B-cell function tests for quantitative immunoglobulins to evaluate for hypogammaglobulinemia and perturbations in T-cell numbers.
  • Bone marrow aspiration helps reveal aplastic anemia or an infiltrative disorder. Bone marrow aspiration may be indicated when patients initially present with pancytopenia.
  • Flow cytometry of blood samples is indicated to look for double negatives.
  • Gene mutation studies are used to detect known condition such as autoimmune lymphoproliferative syndrome.

Procedures

  • Blood tests are typically used to determine the CBC count and reticulocyte count and to perform the Coombs test.
  • Bone marrow aspiration helps in evaluating the morphology and is usually indicated in patients who present with pancytopenia to exclude infiltrative processes.
  • Bone marrow examination is usually not indicated in classic cases when patients present with AIHA or immune thrombocytopenia.

Histologic Findings

  • Bone marrow studies may reveal erythroid hyperplasia and, occasionally, hypoplasia if autoimmune hemolytic anemia (AIHA) is the predominant finding.
  • Normal levels or increased numbers of megakaryocytes confirm that thrombocytopenia is caused by increased destruction in the blood.

More on Evans Syndrome

Overview: Evans Syndrome
Differential Diagnoses & Workup: Evans Syndrome
Treatment & Medication: Evans Syndrome
Follow-up: Evans Syndrome
References
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References

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  2. Wang W, Herrod H, Pui CH. Immunoregulatory abnormalities in Evans syndrome. Am J Hematol. Dec 1983;15(4):381-90. [Medline].

  3. Wang WC. Evans syndrome in childhood: pathophysiology, clinical course, and treatment. Am J Pediatr Hematol Oncol. Winter 1988;10(4):330-8. [Medline].

  4. Savasan S, Warrier I, Ravindranath Y. The spectrum of Evans' syndrome. Arch Dis Child. Sep 1997;77(3):245-8. [Medline].

  5. Teachey DT, Manno CS, Axsom KM, et al. Unmasking Evans syndrome: T-cell phenotype and apoptotic response reveal autoimmune lymphoproliferative syndrome (ALPS). Blood. Mar 15 2005;105(6):2443-8. [Medline].

  6. Pirofsky B. Immune haemolytic disease: the autoimmune haemolytic anaemias. Clin Haematol. Feb 1975;4(1):167-89.

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  8. Habibi B, Homberg JC, Schaison G, Salmon C. Autoimmune hemolytic anemia in children. A review of 80 cases. Am J Med. Jan 1974;56(1):61-9. [Medline].

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  11. Genty I, Michel M, Hermine O, Schaeffer A, Godeau B, Rochant H. [Characteristics of autoimmune hemolytic anemia in adults: retrospective analysis of 83 cases]. Rev Med Interne. Nov 2002;23(11):901-9. [Medline].

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  14. Keung YK, Cobos E, Bolanos-Meade J, et al. Evans syndrome after autologous bone marrow transplant for recurrent Hodgkin's disease. Bone Marrow Transplant. Dec 1997;20(12):1099-101. [Medline].

  15. Yarali, Nese; Demirceken, Fulya; Kondolat, Meda; Ozkasap, Serdar; Kara, Abdurrahman; Tunc, et al. A Rare Condition Associated With Celiac Disease: Evans Syndrome. Journal of Pediatric Hematology/Oncology. September 2007;29 (9):633-635.

  16. Fagiolo E. Platelet and leukocyte antibodies in autoimmune hemolytic anemia. Acta Haematol. 1976;56(2):97-106. [Medline].

  17. Kakaiya RM, Sherman LA, Miller WV, Katz AJ. Nature of platelet antibody in Evans syndrome: a case report. Ann Clin Lab Sci. Nov-Dec 1981;11(6):511-5. [Medline].

  18. Pegels JG, Helmerhorst FM, van Leeuwen EF. The Evans syndrome: characterization of the responsible autoantibodies. Br J Haematol. Jul 1982;51(3):445-50. [Medline].

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  24. Shanafelt TD, Madueme HL, Wolf RC, Tefferi A. Rituximab for immune cytopenia in adults: idiopathic thrombocytopenic purpura, autoimmune hemolytic anemia, and Evans syndrome. Mayo Clin Proc. Nov 2003;78(11):1340-6. [Medline].

  25. Maloney DG, Grillo-Lopez AJ, White CA, et al. IDEC-C2B8 (Rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed low-grade non-Hodgkin's lymphoma. Blood. Sep 15 1997;90(6):2188-95. [Medline].

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  29. Willis F, Marsh JCW, Bevan DH, et al. The effect of treatment with Campath-1H in patients with autoimmune cytopenias. Br J Haematol. 2001;114:891-898.

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  31. Grossi A, Santini V, Longo G, et al. Treatment with anti CD20 antibodies of patients with autoimmune thrombocytopenia with or without hemolytic anemia: worsening in hemoglobin level [abstract]. Blood. 2000;96:1089A.

  32. Avcin T, Jazbec J, Kuhar M, et al. Evans syndrome associated with antiphospholipid antibodies. J Pediatr Hematol Oncol. Sep 2003;25(9):755-6. [Medline].

  33. Chen RT, Pless R, DeStafano F. Epidemiology of autoimmune reactions induced by vaccinations. J Autoimmunity. 2001;16:309-318.

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  35. Miller BA, Schultz Beardsley D. Autoimmune pancytopenia of childhood associated with multisystem disease manifestations. J Pediatr. Dec 1983;103(6):877-81. [Medline].

  36. Petitt RM. Thrombotic thrombocytopenic purpura: a thirty year review. Semin Thromb Hemost. 1980;6(4):350-5. [Medline].

  37. Rosse WF. Paroxysmal nocturnal hemoglobinuria: the biochemical defects and the clinical syndrome. Blood Rev. Sep 1989;3(3):192-200. [Medline].

  38. Sneller MC, Wang J, Dale JK, et al. Clincal, immunologic, and genetic features of an autoimmune lymphoproliferative syndrome associated with abnormal lymphocyte apoptosis. Blood. Feb 15 1997;89(4):1341-8. [Medline].

  39. Tsudo M, Moriguchi T. [Effective cyclosporine therapy to resistant-Evans syndrome]. Rinsho Ketsueki. Nov 1996;37(11):1289-92. [Medline].

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Further Reading

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Keywords

Evans syndrome, ES, autoimmune hemolytic anemia, AIHA, idiopathic thrombocytopenia, ITP, Evans syndrome, autoimmune lymphoproliferative syndrome, ALPS, common variable immunodeficiency, IgA deficiency, diabetes mellitus, Hodgkin disease, Celiac disease, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Prasad Mathew, MBBS, DCh, Director, Hemostasis and Hematology Program, Professor of Pediatrics, University of New Mexico
Prasad Mathew, MBBS, DCh is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Medical Editor

Gary R Jones, MD, Associate Medical Director, Clinical Development, Berlex Laboratories
Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western 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

Gary D Crouch, MD, Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences
Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology
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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