Overview
Cold agglutinin disease (CAD), sometimes called cold agglutinin syndrome or cold antibody hemolytic anemia, is a rare blood disorder where the immune system mistakenly attacks red blood cells. Normally, your immune system protects you from germs. In CAD, it produces special proteins called cold agglutinins — antibodies that become active in cooler temperatures. When parts of your body get cold (like your hands, feet, or even your blood as it circulates near the skin), these antibodies stick to red blood cells and signal the body to destroy them. This process is called hemolysis, and it leads to a shortage of red blood cells, known as anemia. The main symptoms of CAD come from this anemia and from reduced blood flow in cold conditions. People often feel very tired, look pale or yellowish (jaundiced), and notice that their fingers, toes, nose, or ears turn blue or purple in the cold — a condition called acrocyanosis or Raynaud's phenomenon. Some people also have dark-colored urine, especially after cold exposure. CAD can be primary (no known underlying cause, often linked to a small abnormal clone of blood cells in the bone marrow) or secondary (triggered by an infection, another blood cancer, or an autoimmune disease). Treatment has improved significantly in recent years. The drug sutimlimab (Enjaymo) was approved by the FDA in 2022 specifically for CAD, making it the first targeted therapy for this condition. Other treatments include rituximab and bendamustine. Keeping warm is also a key part of daily management.
Key symptoms:
Extreme tiredness and low energy (fatigue from anemia)Pale or yellowish skin (pallor or jaundice)Fingers, toes, nose, or ears turning blue or purple in the cold (acrocyanosis)Dark or tea-colored urine, especially after cold exposureShortness of breath, especially with activityRapid or irregular heartbeatDizziness or lightheadednessFeeling cold all the timeSwollen lymph nodes (in some cases)Abdominal discomfort or enlarged spleen
Clinical phenotype terms (14)— hover any for plain English
Sporadic
Usually appears on its own, not inherited from a parent
Adult
Begins in adulthood (age 18 or older)
FDA & Trial Timeline
10 eventsVirginia Commonwealth University — NA
Queen Mary University of London — NA
Portuguese Association of Interventional Cardiology
Claudia R. Morris — PHASE2
Autus Valve Technologies, Inc. — NA
I.M. Sechenov First Moscow State Medical University
Catharina Ziekenhuis Eindhoven — NA
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
HeartFlow, Inc.
Universitat Internacional de Catalunya — NA
Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.
Treatments
1 availableEnjaymo
indicated for the treatment of hemolysis in adults with cold agglutinin disease (CAD)
Treatment Centers
8 centersBaylor College of Medicine Rare Disease Center ↗
Baylor College of Medicine
📍 Houston, TX
🏥 NORDStanford Medicine Rare Disease Center ↗
Stanford Medicine
📍 Stanford, CA
🔬 UDNNIH Clinical Center Undiagnosed Diseases Program ↗
National Institutes of Health
📍 Bethesda, MD
🔬 UDNUCLA UDN Clinical Site ↗
UCLA Health
📍 Los Angeles, CA
🔬 UDNBaylor College of Medicine UDN Clinical Site ↗
Baylor College of Medicine
📍 Houston, TX
🔬 UDNHarvard/MGH UDN Clinical Site ↗
Massachusetts General Hospital
📍 Boston, MA
🏥 NORDMayo Clinic Center for Individualized Medicine ↗
Mayo Clinic
📍 Rochester, MN
👤 Mayo Clinic Center for Individualized Medicine
🏥 NORDUCLA Rare Disease Day Program ↗
UCLA Health
📍 Los Angeles, CA
Financial Resources
1 resourcesTravel Grants
No travel grants are currently matched to Cold agglutinin disease.
Community
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1 articlesCaregiver Resources
NORD Caregiver Resources
Support, advocacy, and financial assistance for caregivers of rare disease patients.
Mental Health Support
Rare disease caregiving can be isolating. Connect with counseling and peer support.
Family & Caregiver Grants
Financial assistance programs specifically for caregivers of rare disease patients.
Social Security Disability
Learn how rare disease patients may qualify for SSDI/SSI benefits.
Questions for your doctor
Bring these to your next appointment
- Q1.Is my CAD primary or secondary, and does that change my treatment options?,Am I a candidate for sutimlimab (Enjaymo), and how would I receive it?,How cold is too cold for me, and what specific precautions should I take in daily life?,What signs should prompt me to go to the emergency room?,How often will I need blood tests to monitor my condition?,Are there any clinical trials I should consider?,Should I avoid any vaccines, medications, or procedures that could trigger a flare?
Common questions about Cold agglutinin disease
What is Cold agglutinin disease?
Cold agglutinin disease (CAD), sometimes called cold agglutinin syndrome or cold antibody hemolytic anemia, is a rare blood disorder where the immune system mistakenly attacks red blood cells. Normally, your immune system protects you from germs. In CAD, it produces special proteins called cold agglutinins — antibodies that become active in cooler temperatures. When parts of your body get cold (like your hands, feet, or even your blood as it circulates near the skin), these antibodies stick to red blood cells and signal the body to destroy them. This process is called hemolysis, and it leads t
How is Cold agglutinin disease inherited?
Cold agglutinin disease follows a sporadic inheritance pattern. Genetic counseling can help families understand recurrence risk and testing options.
At what age does Cold agglutinin disease typically begin?
Typical onset of Cold agglutinin disease is adult. Age of onset can vary across affected individuals.
Are there clinical trials for Cold agglutinin disease?
Yes — 2 recruiting clinical trials are currently listed for Cold agglutinin disease on UniteRare. See the clinical trials section on this page for phase, sponsor, and site details sourced from ClinicalTrials.gov.
Which specialists treat Cold agglutinin disease?
25 specialists and care centers treating Cold agglutinin disease are listed on UniteRare, sourced from ClinicalTrials.gov principal investigators, published research, and the NPPES NPI registry.