Pediatric Cold Agglutinin Disease Treatment & Management

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

Medical Care

Treatment of cold agglutinin disease depends on severity of the disease and presence of an underlying cause.

In children, cold agglutinin disease is usually mild and self-limited, requiring little, if any, intervention.

Supportive care measures include avoiding exposure to cold and judicious use of RBC transfusions. RBC transfusion is indicated in acute severe disease. Compatibility testing is performed using the techniques described above to minimize the interference caused by the cold agglutinin (see Workup). Blood warmers are used to perform the transfusion at 37ºC.

The response to transfused RBCs may be transient but can result in significant improvement in an acutely ill patient.

Viral infections, such as Epstein-Barr virus (EBV), cytomegalovirus (CMV), and the mumps, are usually self-limited. Causes such as mycoplasma infection, systemic autoimmune disease, or lymphoproliferative disease must be treated.

Prednisone therapy is seldom effective. Certain patients may respond to prednisone therapy, such as those who have the variant of cold agglutinin disease characterized by a low cold agglutinin titer and high thermal amplitude.

Plasmapheresis may serve as a temporizing measure in severe cases of acute disease.[2] Because immunoglobulin M (IgM) is confined to the intravascular space, plasmapheresis can reduce the autoantibody level; however, this reduction is very transient because of the continued production of autoantibody. The use of this procedure is very limited.

The anti-CD20 monoclonal antibody rituximab depletes B-lymphocytes and, thereby, interferes with the production of cold agglutinin. Rituximab has been studied in children with autoimmune hemolytic anemia and other immune mediated cytopenias.[3] Although it has been found to be an effective treatment for these autoimmune cytopenias, no controlled studies specific to its use in refractory cold agglutinin disease in childhood have been reported.

Berentsen et al reported good response to the combination of fludarabine and rituximab in adult patients with primary cold agglutinin disease.[4]

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Surgical Care

Splenectomy is ineffective because the liver is the predominant site of hemolysis.

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Consultations

Consult a hematologist and/or blood bank specialist to aid in diagnostic workup and management.

Initial care for children with cold agglutinin is to warm the patient and the fluids/blood products entering the child to minimize antibody binding. This may entail use of special rooms with independent heat and air conditioning controls, heating blankets or Bear huggers, and fluid warmers. Close cooperation with the hospital nursing staff and central supply facilitates speedy initiation of these therapies.

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Activity

Patients with anemia should avoid strenuous exercise.

Prevent hypothermia and exposure to cold.

Migration to avoid winter may be advisable.

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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

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  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].

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  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].

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  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].

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Blood smear showing spherocytic and agglutinated RBCs.
 
 
 
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