Pediatric Cold Agglutinin Disease Workup

  • Author: James L Harper, MD; Chief Editor: Max J Coppes, MD, PhD, MBA   more...
 
Updated: Aug 3, 2011
 

Laboratory Studies

The following studies may be indicated in patients with cold agglutinin disease:

Hematology

Anemia is usually mild. Exposure to cold may significantly worsen anemia. The mean corpuscular volume (MCV) is elevated because of reticulocytosis and to agglutination of the RBCs.

Reticulocytosis may be inadequate for the degree of anemia. This may be due to decreased erythropoiesis caused by the underlying infection.

Smear shows spherocytosis, polychromatophilia, and RBC agglutination.

Marrow examination reveals erythroid hyperplasia and lymphocytosis. These lymphocytes have cold agglutinin as surface immunoglobulin. Marrow examination is usually unnecessary.

Blood bank

Blood typing is performed in the event that a transfusion is needed. The presence of autoantibodies may interfere with blood typing. The autoantibody may react with the RBCs of all potential donors, making detection of alloantibodies difficult. Several techniques are available to improve compatibility testing. These techniques include testing the patient's serum for anti-A and anti-B hemagglutinins and performing the compatibility testing reactions at 37ºC.

Direct antiglobulin test (DAT) is positive with anti-C3 and negative with anti-IgG. The autoantibody is usually an immunoglobulin M (IgM), but mixed immunoglobulin G (IgG)/IgM and occasionally immunoglobulin A (IgA) cold agglutinins can be present.

Transient cold agglutinin disease is characterized by a moderately elevated cold agglutinin titer (1:1,000-20,000) and polyclonal cold agglutinins. The autoantibodies are anti-I in M pneumoniae infections and anti-i in Epstein-Barr virus (EBV) infections. The autoantibodies appear 2-3 weeks after onset of symptoms and disappear in 2-3 months.

In chronic cold agglutinin disease, the cold agglutinin titer is very high (>1:100,000-1,000,000), and the cold agglutinins are monoclonal. In chronic cold agglutinin disease associated with monoclonal gammopathy and with chronic lymphocytic leukemia, the autoantibodies are monoclonal anti-I. In chronic cold agglutinin disease associated with malignant lymphomas, the autoantibodies are monoclonal anti-i.

The autoantibodies are more reactive in the cold with diminishing reactivity as the temperature approaches 37ºC. Indirect antiglobulin test results at 37ºC are negative.

A variant of cold agglutinin disease occurs in some patients. This variant is characterized by more severe disease, low cold agglutinin titer, and autoantibody with high thermal amplitude.

Bilirubin, lactic dehydrogenase (LDH), and plasma hemoglobin

Indirect bilirubin, LDH, and plasma hemoglobin levels are moderately elevated.

Urinalysis

Urinalysis reveals hemoglobinuria, hemosiderinuria, and elevated urobilinogen.

Serology findings

Serology findings for mycoplasma, EBV, or cytomegalovirus (CMV) may be positive depending on the underlying cause.

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Imaging Studies

A chest radiograph is obtained if pneumonia is suspected.

Chest radiography shows pulmonary infiltrates in cases of infection with M pneumoniae.

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Contributor Information and Disclosures
Author

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 School of Medicine; 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.

Specialty Editor Board

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.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

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.

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

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Khan FY, A yassin M. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: case report and literature review. Braz J Infect Dis. Feb 2009;13(1):77-9. [Medline].

  2. Roy-Burman A, Glader BE. Resolution of severe Donath-Landsteiner autoimmune hemolytic anemia temporally associated with institution of plasmapheresis. Crit Care Med. Apr 2002;30(4):931-4. [Medline].

  3. Giulino LB, Bussel JB, Neufeld EJ. Treatment with rituximab in benign and malignant hematologic disorders in children. J Pediatr. Apr 2007;150(4):338-44, 344.e1. [Medline].

  4. Berentsen S, Randen U, Vågan AM, Hjorth-Hansen H, Vik A, Dalgaard J, et al. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. Oct 28 2010;116(17):3180-4. [Medline].

  5. [Best Evidence] [Guideline] Berentsen S. How I manage cold agglutinin disease. Br J Haematol. May 2011;153(3):309-17. [Medline].

  6. Berentsen S, Ulvestad E, Gjertsen BT, et al. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. Apr 15 2004;103(8):2925-8. [Medline]. [Full Text].

  7. Camou F, Viallard JF, Pellegrin JL. [Rituximab in cold agglutinin disease]. Rev Med Interne. Aug 2003;24(8):501-4. [Medline].

  8. Cushing M, Degtyaryova D, Lomas-Francis C. Transfusion medicine illustrated. The role of plasmapheresis in the multimodal treatment of anti-Pr cold agglutinin disease. Transfusion. Oct 2010;50(10):2100-1. [Medline].

  9. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol. Apr 2002;69(4):258-71. [Medline].

  10. Gertz MA. Cold agglutinin disease and cryoglobulinemia. Clin Lymphoma. Mar 2005;5(4):290-3. [Medline].

  11. Hadnagy C. Agewise distribution of idiopathic cold agglutinin disease. Z Gerontol. May-Jun 1993;26(3):199-201. [Medline].

  12. Hamblin T. Management of cold agglutination syndrome. Transfus Sci. Feb-Apr 2000;22(1-2):121-4. [Medline].

  13. Inaba H, Geiger TL, Lasater OE, Wang WC. A case of hemoglobin SC disease with cold agglutinin-induced hemolysis. Am J Hematol. Jan 2005;78(1):37-40. [Medline].

  14. McNicholl FP. Clinical syndromes associated with cold agglutinins. Transfus Sci. Feb-Apr 2000;22(1-2):125-33. [Medline].

  15. Nanan R, Scheurlen W, Gerlich M, Huppertz HI. Severe low-titer cold-hemagglutinin disease responsive to steroid pulse therapy. Ann Hematol. Aug 1995;71(2):101-2. [Medline].

  16. Ness PM, Bell WR, Shirey RS. Transfusion medicine illustrated. Novel management of cold agglutinin disease. Transfusion. Jul 2003;43(7):839. [Medline].

  17. Ng PC, Lee KK, Lo AF, Li CK, Fok TF. Anti B cell targeted immunotherapy for treatment of refractory autoimmune haemolytic anaemia in a young infant. Arch Dis Child. Apr 2003;88(4):337-9. [Medline].

  18. Nydegger UE, Kazatchkine MD, Miescher PA. Immunopathologic and clinical features of hemolytic anemia due to cold agglutinins. Semin Hematol. Jan 1991;28(1):66-77. [Medline].

  19. Potter KN. Molecular characterization of cold agglutinins. Transfus Sci. Feb-Apr 2000;22(1-2):113-9. [Medline].

  20. Rituxan Product Information Sheet. FDA: FDA; 2002. [Full Text].

  21. Rosse WF, Hillmen P, Schreiber AD. Immune-mediated hemolytic anemia. Hematology (Am Soc Hematol Educ Program). 2004;48-62. [Medline].

  22. Stone MJ. Heating up cold agglutinins. Blood. Oct 28 2010;116(17):3119-20. [Medline].

  23. Teachey DT, Felix CA. Development of cold agglutinin autoimmune hemolytic anemia during treatment for pediatric acute lymphoblastic leukemia. J Pediatr Hematol Oncol. Jul 2005;27(7):397-9. [Medline].

  24. Terada K, Tanaka H, Mori R, et al. Hemolytic anemia associated with cold agglutinin during chickenpox and a review of the literature. J Pediatr Hematol Oncol. Mar-Apr 1998;20(2):149-51. [Medline].

  25. Vassou A, Alymara V, Chaidos A, Bourantas KL. Beneficial effect of rituximab in combination with oral cyclophosphamide in primary chronic cold agglutinin disease. Int J Hematol. Jun 2005;81(5):421-3. [Medline].

  26. Zecca M, Nobili B, Ramenghi U, Perrotta S, Amendola G, Rosito P, et al. Rituximab for the treatment of refractory autoimmune hemolytic anemia in children. Blood. May 15 2003;101(10):3857-61. [Medline].

 
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Blood smear showing spherocytic and agglutinated RBCs.
 
 
 
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