eMedicine Specialties > Hematology > Red Blood Cells and Disorders

Cold Agglutinin Disease: Follow-up

Author: Sharon Georgy, MD, Resident Physician, Department of Internal Medicine, University of South Florida
Coauthor(s): Richard F Lockey, MD, University Distinguished Health Professor, Professor of Medicine, Pediatrics and Public Health, Joy McCann Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine; Director, Division of Allergy and Immunology, James A Haley Veterans' Hospital; Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems; Harry L Messmore, Jr, MD, Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine
Contributor Information and Disclosures

Updated: Feb 16, 2009

Follow-up

Further Inpatient Care

  • In patients with cold agglutinin disease, transfusions should be used only for symptomatic anemia or an acute life-threatening drop in hemoglobin or hematocrit value.

Further Outpatient Care

  • Provide follow-up care after in-hospital therapy. Long-term follow-up care, with or without therapy, is important to monitor for the development of any additional illnesses, such as a lymphoproliferative disorder, that would require specific therapy.
  • Provide patients with cold agglutinin disease with periodic follow-up care to monitor for signs of worsening or improvement that might prompt changes in management. The frequency of reassessment varies with the severity of the disease. Periodic checkups might vary from daily to weekly or monthly and eventually as infrequently as every 2-3 months. Make reevaluations more often in colder weather than in warmer weather.
  • Unless a clear-cut need exists, limit the use of medications in persons with cold agglutinin disease.
  • Monitor blood cell counts and observe for infection, renal function, development of lymphoma, and evidence of ischemia.
  • Avoid exposing patients to cold, as can occur with patients waiting to undergo operative procedures. Avoid cooling blankets for any reason.

Inpatient & Outpatient Medications

  • Folic acid 1 mg PO qd

Transfer

  • If an institution is unable to handle the needs of a patient with a high titer, high thermal amplitude – cold agglutinin hemolytic anemia who requires open heart surgery, which is usually performed under hypothermic conditions, and monitoring of thermal amplitude and core body temperature, transfer is necessary. Consultation with a hematologist and the support of a blood bank are also required.
  • An alternative that may be used to induce cardiac arrest during cardiac surgery is continuous perfusion with normothermic, hyperkalemic blood during the cross-clamp period.54 (Such precautions must be taken in order to avoid hemolysis, renal failure, and myocardial damage in patients with cold agglutinin disease.55

Deterrence/Prevention

  • Protective measures include avoidance of cold by covering the hands, feet, and, if possible, the face in cold weather or low windchill temperatures. An exact temperature cannot be defined because symptoms are due to the thermal amplitude and other characteristics of the antibody. In some individuals, a windchill temperature of 15°C, if sustained, precipitates symptoms; more commonly, a lower temperature of 10°C would precipitate symptoms. Sleeping uncovered may result in symptoms when the room temperature is 21°C.
  • Recommendations to move to a warm climate have merit in more severe cases in which symptoms and hemolysis are less likely to develop at higher ambient temperatures.
  • Avoidance of cold temperatures and adequate protection of all body parts from the cold helps to prevent the development of hemolysis.
  • Idiopathic cold agglutinin disease itself cannot be prevented.
  • The use of a cooling blanket may precipitate gangrene in rare cases.

Complications

  • Brisk hemolysis due to cold exposure
  • Ischemic complications at exposed sites due to prolonged cold exposure
  • Other symptoms related to severe anemia
  • Infrequently, development of malignant disease during follow-up care of a patient with idiopathic chronic cold agglutinin disease

Prognosis

  • Cold agglutinin disease may be associated with an excellent long-term prognosis if it is secondary to M pneumonia or viral infections that are, in themselves, self-limited.
  • Patients with the mildly to moderately severe idiopathic or primary variety of cold agglutinin disease are expected to have a good long-term prognosis if excessive exposure to cold is avoided and with close medical surveillance for complications or progression to lymphoma.
  • The nature of the antigenic specificity of the cold agglutinin, as when it is directed against the Pr system, may be associated with greater severity of disease.
  • Cold agglutinin disease associated with HIV infection may have a relatively poor prognosis due to the nature of the underlying disease.
    • The same applies for lymphoma, with prognosis dependent on remission of the underlying lymphoma.

Patient Education

  • Educating patients with cold agglutinin disease about the importance of keeping all body parts warm at all times and avoiding cooling of body parts is essential in a chronic disorder. Appropriate clothing is necessary in cold environments.
  • Patients must comprehend the importance of daily intake of folic acid to supply a needed hematinic. Folic acid could easily become a rate-limiting hematinic in a patient with a chronic hemolytic process.
  • Long-term follow-up care and vigilance for the development of systemic symptoms of any lymphoproliferative disorder are necessary, because patients may become dejected about a chronic process.
  • Avoidance of cold foods and working in cold storages is also important.

Miscellaneous

Medicolegal Pitfalls

  • Ensure proper handling of specimens when looking for cold agglutinins (ie, keeping the blood warm until it is tested). Blood specimens are commonly placed in a laboratory refrigerator until they are tested. This practice must be avoided when testing for cold agglutinins.
  • Typing and cross-matching should be performed with blood at 37°C to avoid inaccurate test results due to nonspecific agglutination in the cold.
  • Perform IgG and complement Coombs tests to detect the presence of complement on the RBCs.
  • Chemotherapeutic agents should be used only for serious complications, following a discussion with the patient and consultant regarding potential risks.
  • Postinfectious anemia, infectious mononucleosis, M pneumoniae infection, acrocyanosis, or cold-precipitated symptoms are clues that require follow-up care.
  • Careful planning and coordination with multiple personnel are needed if patients are to undergo a procedure during which their body temperature could fall.

Special Concerns

  • Preparative management of a patient for open-heart surgery requires reduction in the titer of the cold agglutinin so that the thermal amplitude is not high. This can be achieved with plasmapheresis, as discussed in Treatment. The laboratory could help to assess the temperature range of activity of the cold agglutinin after the titer has been reduced so that a minimum target temperature may be estimated. Core body temperatures may require close monitoring.
  • When cold-induced autoimmune hemolytic anemia occurs in pregnant women, the pregnancy may be continued with frequent blood transfusions. Transfusions may be continued until the 37th week, when fetal lungs have matured. Mode of delivery is not affected by the anemia and should be defined by obstetric indications. Ironically, these women are still subject to thrombophlebitis of pregnancy.56
 


More on Cold Agglutinin Disease

Overview: Cold Agglutinin Disease
Differential Diagnoses & Workup: Cold Agglutinin Disease
Treatment & Medication: Cold Agglutinin Disease
Follow-up: Cold Agglutinin Disease
Multimedia: Cold Agglutinin Disease
References
Further Reading
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Further Reading

Related eMedicine Topics

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Keywords

cold agglutinin disease, cold agglutinin hemolytic anemia, idiopathic acquired hemolytic anemia, autoimmune hemolytic anemia, hemolytic anemia, CAD, acrocyanosis, cold-induced immune hemolytic anemia, mixed autoimmune hemolysis,
Mycoplasma pneumoniae, M pneumoniae, infectious mononucleosis, Epstein-Barr virus, EBV, influenza, human immunodeficiency virus, HIV, cytomegalovirus, CMV, rubella, varicella, varicella zoster virus, mumps, subacute bacterial endocarditis, syphilis, malaria, equestrian perniosis,

lymphoma, Waldenstrom syndrome, chronic lymphocytic leukemia, CLL, lymphoproliferative disease, autoimmune disease, myeloma, Kaposi sarcoma, Kaposi's sarcoma, angioimmunoblastic lymphoma

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Contributor Information and Disclosures

Author

Sharon Georgy, MD, Resident Physician, Department of Internal Medicine, University of South Florida
Sharon Georgy, MD is a member of the following medical societies: Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Richard F Lockey, MD, University Distinguished Health Professor, Professor of Medicine, Pediatrics and Public Health, Joy McCann Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine; Director, Division of Allergy and Immunology, James A Haley Veterans' Hospital
Richard F Lockey, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American College of Chest Physicians, American College of Occupational and Environmental Medicine, American College of Physicians, American Medical Association, and Florida Medical Association
Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Harry L Messmore, Jr, MD, Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine
Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Association, American Society of Hematology, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

Jeffrey Lee Kishiyama, MD, Assistant Clinical Professor of Medicine, University of California at San Francisco School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center
Disclosure: Nothing to disclose.

Pharmacy Editor

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

Managing Editor

Samuel R Marney, Jr, MD, Director, Associate Professor, Department of Internal Medicine, Division of Allergy and Immunology, Vanderbilt University School of Medicine
Samuel R Marney, Jr, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American College of Physicians, and Tennessee Medical Association
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD, Clinical Professor of Medicine, George Washington University School of Medicine; Chief, Section of Allergy and Immunology, Washington Hospital Center; Medical Director, Institute for Asthma and Allergy
Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, and Association of American Physicians
Disclosure: Abbott Consulting fee Consulting; Alcon Consulting fee Consulting; Glaxo Consulting fee Consulting; Greer Consulting fee Consulting; Sanofi Consulting fee Consulting; Schering Consulting fee Consulting; Teva  Consulting; Meda Honoraria Speaking and teaching

 
 
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