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Cold Agglutinin Disease Clinical Presentation

  • Author: Salman Abdullah Aljubran, MD; Chief Editor: Michael A Kaliner, MD  more...
 
Updated: Jul 20, 2016
 

History

A common complaint among patients with cold agglutinin disease is painful fingers and toes with purplish discoloration associated with cold exposure. In chronic cold agglutinin disease, the patient is more symptomatic during the colder months.

Cold agglutinin–mediated acrocyanosis differs from Raynaud phenomenon. In Raynaud phenomena, caused by vasospasm, a triphasic color change occurs, from white to blue to red, based on vasculature response. No evidence of such a response exists in cold agglutinin disease.[25]

Other symptoms of cold agglutinin disease include the following:

  • Respiratory symptoms - May be present in patients with Mycoplasma pneumoniae infection
  • Hemoglobinuria (the passage of dark urine that contains hemoglobin) - A rare symptom that results from hemolysis, this may be reported following prolonged exposure to cold; hemoglobinuria is more commonly seen in paroxysmal cold hemoglobinuria
  • Chronic fatigue - Due to anemia

Anemia in patients with cold agglutinin disease may be mild, moderate, or severe. Along with fatigue, symptoms of anemia include pallor, dyspnea, and poor feeding.

Other symptoms of cold agglutinin disease, such as a history of weight loss and adenopathy, can be related to the underlying disease state associated with the production of cold agglutinins.

The severity of the clinical manifestations of the cold agglutinins themselves varies from an inconsequential laboratory finding, in cases of the benign variety, to serious manifestations, such as acute hemolytic crises and Raynaud-type phenomena, in cases of the more malignant variety.

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Physical Examination

Physical examination may reveal nothing unusual or only pallor, unless the patient is observed during or shortly after cold exposure. Purplish discoloration of the ears, forehead, tip of the nose, and digits may then be seen. Livedo reticularis has been observed as well. Ischemic necrosis can lead to pain, but skin ulceration secondary to ischemia is uncommon.

Splenomegaly and jaundice, characteristic of lymphoproliferative disorders or infectious mononucleosis, are usually absent, but they may sometimes be observed in patients with chronic cold agglutinin disease.

Lymphadenopathy, fever, or both may be present in patients with lymphoma, infectious mononucleosis, or other infections.

Pulmonary signs, such as rales and fever, may be found in patients with Mycoplasma pneumonia.[27, 15, 47] Other findings, including hepatomegaly, relate to the presence of underlying or associated disease states. Signs of congestive heart failure or shock are rare but may be present when anemia is severe.

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Contributor Information and Disclosures
Author

Salman Abdullah Aljubran, MD Clinical Fellow, Division of Allergy and Immunology, University of South Florida College of Medicine

Salman Abdullah Aljubran, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American Thoracic Society, Massachusetts Medical Society

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 Occupational and Environmental Medicine, American College of Chest Physicians, American College of Physicians, American Medical Association, Florida Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; 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, Association of American Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Nicolas A Camilo, MD Consulting Staff, Mountain States Tumor Institute, Division of Pediatric Hematology-Oncology, St Luke's Regional Medical Center

Disclosure: Nothing to disclose.

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.

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.

Sharon Georgy, MD Resident Physician, Department of Internal Medicine, University of South Florida College of Medicine

Sharon Georgy, MD is a member of the following medical societies: Phi Beta Kappa

Disclosure: Nothing to disclose.

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.

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.

Jeffrey Lee Kishiyama, MD Assistant Clinical Professor of Medicine, University of California, San Francisco, School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center

Disclosure: Nothing to disclose.

Thomas W Loew, MD Director, Clinical Associate Professor of Pediatrics, Pediatric Hematology/Oncology Subspecialty Training Program, University of Iowa Hospitals and Clinics

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.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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.

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Peripheral blood smear showing several clumps of RBCs with the largest in the center. These are typical of aggregates seen in persons with cold agglutinin disease.
Blood smear showing spherocytic and agglutinated red blood cells.
 
 
 
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