CAD
MCID: CLD007
MIFTS: 43

Cold Agglutinin Disease (CAD)

Categories: Blood diseases, Immune diseases, Rare diseases

Aliases & Classifications for Cold Agglutinin Disease

MalaCards integrated aliases for Cold Agglutinin Disease:

Name: Cold Agglutinin Disease 20 58
Chronic Cold Agglutinin Disease 58 70
Cad 20 58
Anemia, Hemolytic, Cold Antibody 20
Cold Antibody Hemolytic Anemia 20
Cold Hemagglutinin Disease 70
Cold Agglutinin Syndrome 58
Cold Antibody Disease 20
Cas 58

Characteristics:

Orphanet epidemiological data:

58
cold agglutinin disease
Inheritance: Multigenic/multifactorial; Age of onset: Adult; Age of death: elderly;

Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

ICD10 via Orphanet 33 D59.1
UMLS via Orphanet 71 C0175816
Orphanet 58 ORPHA56425
UMLS 70 C0175816 C1264008

Summaries for Cold Agglutinin Disease

GARD : 20 Cold agglutinin disease is a rare type of autoimmune hemolytic anemia in which the body's immune system mistakenly attacks and destroys its own red blood cells. When affected people's blood is exposed to cold temperatures (32o to 50o F), certain proteins that normally attack bacteria (IgM antibodies ) attach themselves to red blood cells and bind them together into clumps (agglutination). This eventually causes red blood cells to be prematurely destroyed (hemolysis) leading to anemia and other associated signs and symptoms. Cold agglutinin disease can be primary (unknown cause) or secondary, due to an underlying condition such as an infection, another autoimmune disease, or certain cancers. Treatment depends on many factors including the severity of the condition, the signs and symptoms present in each person, and the underlying cause.

MalaCards based summary : Cold Agglutinin Disease, also known as chronic cold agglutinin disease, is related to chickenpox and exanthem. An important gene associated with Cold Agglutinin Disease is CARD11 (Caspase Recruitment Domain Family Member 11), and among its related pathways/superpathways is Overview of nanoparticle effects. The drugs Agglutinins and Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include lung, bone and heart, and related phenotypes are muscle weakness and fatigue

Wikipedia : 73 Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high... more...

Related Diseases for Cold Agglutinin Disease

Diseases related to Cold Agglutinin Disease via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 722)
# Related Disease Score Top Affiliating Genes
1 chickenpox 30.3 IL6 CRP
2 exanthem 30.2 IL6 CRP
3 purpura 30.1 IL6 CRP
4 pleural empyema 30.1 IL6 CRP
5 polyclonal hypergammaglobulinemia 30.1 IL6 CRP
6 thyroiditis 30.1 IL6 CRP
7 waldenstroem's macroglobulinemia 30.0 MS4A1 IGHM
8 leptospirosis 30.0 IL6 CRP
9 syphilis 30.0 IL6 CRP
10 obstructive jaundice 29.9 IL6 CRP
11 pericarditis 29.9 IL6 CRP
12 bronchiolitis obliterans 29.9 IL6 CRP
13 temporal arteritis 29.9 IL6 CRP
14 acute cystitis 29.8 IL6 CRP
15 bronchopneumonia 29.8 IL6 CRP
16 aspiration pneumonia 29.8 IL6 CRP
17 streptococcus pneumonia 29.8 IL6 CRP
18 pyelonephritis 29.8 IL6 CRP
19 typhoid fever 29.6 IL6 CRP
20 vaginal discharge 29.6 IL6 CRP
21 compartment syndrome 29.6 IL6 CRP
22 osteomyelitis 29.6 IL6 CRP
23 klebsiella pneumonia 29.6 IL6 CRP
24 lymphoma 29.6 MS4A1 KMT2D IL6 CARD11
25 angina pectoris 29.5 IL6 CRP
26 perinatal necrotizing enterocolitis 29.5 IL6 CRP
27 dysentery 29.5 IL6 CRP
28 adult-onset still's disease 29.5 IL6 CRP
29 pericardial effusion 29.5 IL6 CRP
30 coronary stenosis 29.4 IL6 CRP
31 childhood apraxia of speech 11.4
32 anemia, autoimmune hemolytic 11.3
33 warm antibody hemolytic anemia 11.2
34 palmoplantar keratoderma and congenital alopecia 2 11.0
35 hemolytic anemia 10.9
36 adenoma 10.8
37 hepatocellular adenoma 10.6
38 lymphoproliferative syndrome 10.5
39 keratosis 10.5
40 48,xyyy 10.5
41 47,xyy 10.5
42 deficiency anemia 10.5
43 squamous cell papilloma 10.5
44 papilloma 10.5
45 b-cell lymphoma 10.4
46 raynaud phenomenon 10.4
47 carotid stenosis 10.4
48 thrombocytopenia 10.4
49 cryoglobulinemia 10.4
50 macroglobulinemia 10.4

Graphical network of the top 20 diseases related to Cold Agglutinin Disease:



Diseases related to Cold Agglutinin Disease

Symptoms & Phenotypes for Cold Agglutinin Disease

Human phenotypes related to Cold Agglutinin Disease:

58 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 muscle weakness 58 31 hallmark (90%) Very frequent (99-80%) HP:0001324
2 fatigue 58 31 hallmark (90%) Very frequent (99-80%) HP:0012378
3 autoimmunity 58 31 hallmark (90%) Very frequent (99-80%) HP:0002960
4 pallor 58 31 hallmark (90%) Very frequent (99-80%) HP:0000980
5 hemolytic anemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001878
6 arthralgia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002829
7 nausea and vomiting 58 31 occasional (7.5%) Occasional (29-5%) HP:0002017
8 splenomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001744
9 hepatomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002240
10 back pain 58 31 occasional (7.5%) Occasional (29-5%) HP:0003418
11 headache 58 31 occasional (7.5%) Occasional (29-5%) HP:0002315
12 abnormal urinary color 58 31 occasional (7.5%) Occasional (29-5%) HP:0012086
13 diarrhea 58 31 occasional (7.5%) Occasional (29-5%) HP:0002014
14 lymphadenopathy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002716

Drugs & Therapeutics for Cold Agglutinin Disease

Drugs for Cold Agglutinin Disease (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 15)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1 Agglutinins Phase 3
2 Pharmaceutical Solutions Phase 3
3
rituximab Approved Phase 2 174722-31-7 10201696
4
Fludarabine Approved Phase 2 21679-14-1, 75607-67-9 30751
5
Acyclovir Approved Phase 2 59277-89-3 2022
6
Bortezomib Approved, Investigational Phase 2 179324-69-7 387447 93860
7 Antineoplastic Agents, Immunological Phase 2
8 Antirheumatic Agents Phase 2
9 Immunologic Factors Phase 2
10 Alkylating Agents Phase 2
11 Bendamustine Hydrochloride Phase 2
12 Immunoglobulins Phase 2
13 Antibodies, Monoclonal Phase 2
14 Antibodies Phase 2
15 Complement System Proteins Phase 2

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase 3, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Without a Recent History of Blood Transfusion Active, not recruiting NCT03347422 Phase 3 sutimlimab (BIVV009);placebo
2 A Phase 3, Pivotal, Open-label, Multicenter Study to Assess the Efficacy and Safety of Sutimlimab in Patients With Primary Cold Agglutinin Disease Who Have a Recent History of Blood Transfusion Active, not recruiting NCT03347396 Phase 3 Sutimlimab
3 Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-Randomized Multi-Center Study Demonstrating the Efficacy of Terminal Complement Inhibition in Patients With Cold Agglutinin Disease Using Eculizumab Completed NCT01303952 Phase 2 Eculizumab
4 The CAD5 Study::Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicenter Trial on the Safety and Efficacy of Bendamustine and Rituximab Combination Therapy Completed NCT02689986 Phase 2 Bendamustine, Rituximab
5 Therapy for Chronic Cold Agglutinin Disease: A Prospective, Non-randomized International Multicentre Study on the Safety and Efficacy of Rituximab in Combination With Fludarabine. Completed NCT00373594 Phase 2 Rituximab;Fludarabine
6 Short Course of Bortezomib in Anemic Patients With Refractory Cold Agglutinin Disease Completed NCT01696474 Phase 2 Bortezomib
7 An Open Label, Prospective, Study to Assess the Safety, Tolerability, Efficacy and Pharmacokinetics of APL-2 in Patients With Warm Type Autoimmune Hemolytic Anemia (wAIHA) or Cold Agglutinin Disease (CAD) Active, not recruiting NCT03226678 Phase 2 APL-2
8 A Multicenter, Phase 1b, Open Label, Nonrandomized, Single Dose Study Evaluating the Safety, Tolerability and Activity of BIVV020 in Adults With Cold Agglutinin Disease Recruiting NCT04269551 Phase 1 BIVV020
9 An Open Label, Long Term, Safety and Tolerability Study of Patients With Cold Agglutinin Disease Previously Treated With BIVV020 Recruiting NCT04802057 Phase 1 BIVV020

Search NIH Clinical Center for Cold Agglutinin Disease

Genetic Tests for Cold Agglutinin Disease

Anatomical Context for Cold Agglutinin Disease

MalaCards organs/tissues related to Cold Agglutinin Disease:

40
Lung, Bone, Heart, Skin, Bone Marrow, Kidney, Thyroid

Publications for Cold Agglutinin Disease

Articles related to Cold Agglutinin Disease:

(show top 50) (show all 448)
# Title Authors PMID Year
1
Cold agglutinin-mediated autoimmune hemolytic anemia. 20 61
26043385 2015
2
Multifocal thrombosis with peripheral gangrene in a young boy: Mycoplasma infection triggered cold agglutinin disease. 61
33711641 2021
3
MASS-FIX for the detection of monoclonal proteins and light chain N-glycosylation in routine clinical practice: a cross-sectional study of 6315 patients. 61
33664227 2021
4
How I treat cold agglutinin disease. 61
33512410 2021
5
In from the cold: M-protein light chain glycosylation is positively associated with cold agglutinin titer levels. 61
33502021 2021
6
The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease. 61
33732266 2021
7
Features of serum complement C3 and C4 levels in autoimmune hemolytic anemia patients. 61
33459487 2021
8
Rituximab Use in Warm and Cold Autoimmune Hemolytic Anemia. 61
33322221 2020
9
Unusual co-occurrence of cold agglutinin disease in a bladder transitional cell carcinoma patient with unexplained anemia and cold-related symptoms. 61
33323815 2020
10
Perioperative management of a patient with severe cold agglutinin disease by using multimodal warming measures. 61
33285047 2020
11
Cold Agglutinin Disease and Hemolytic Crisis After Hypothermic Circulatory Arrest in a Patient With Beta-Thalassemia Minor. 61
32245720 2020
12
Autoimmune hemolytic anemia: current knowledge and perspectives. 61
33292368 2020
13
Serological Blood Group Discrepancy and Cold Agglutinin Autoimmune Hemolytic Anemia Associated With Novel Coronavirus. 61
33354441 2020
14
New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy Stage 1. 61
33261023 2020
15
Cold agglutinin disease in an infant: remission after intravenous immunoglobulin. 61
33034109 2020
16
Demographic characteristics, thromboembolism risk, and treatment patterns for patients with cold agglutinin disease in Japan. 61
32608010 2020
17
Pembrolizumab-Induced Cold Agglutinin Disease. 61
32887867 2020
18
Glycosylation of immunoglobulin light chains is highly prevalent in cold agglutinin disease. 61
32356376 2020
19
Healthcare resource utilization among commercially insured patients with cold agglutinin disease in the United States. 61
32362156 2020
20
SARS-CoV-2-associated cold agglutinin disease: a report of two cases. 61
32591877 2020
21
Cold agglutinin disease following SARS-CoV-2 and Mycoplasma pneumoniae co-infections. 61
32837721 2020
22
Do temperature and time matter in cold agglutinin disease? 61
32702122 2020
23
Lessons of the month 1: Polytrauma in a geriatric patient resulting in reactivation of cytomegalovirus infection and secondary cold agglutinin disease-induced haemolytic anaemia. 61
32554607 2020
24
Rituximab-containing therapy for cold agglutinin disease: a retrospective study of 16 patients. 61
32728060 2020
25
Cold agglutinin disease revisited: a multinational, observational study of 232 patients. 61
32374875 2020
26
Cold agglutinin disease and autoimmune hemolytic anemia with pulmonary embolism as a presentation of COVID-19 infection. 61
32645300 2020
27
Daratumumab for disabling cold agglutinin disease refractory to B-cell directed therapy. 61
32652632 2020
28
Current advances in transfusion medicine: a 2019 review of selected topics from the AABB Clinical Transfusion Medicine Committee. 61
32472580 2020
29
Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. 61
31839434 2020
30
Increased risk of thrombotic events in cold agglutinin disease: A 10-year retrospective analysis. 61
32548562 2020
31
Complementopathies and precision medicine. 61
32310222 2020
32
Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program. 61
32176765 2020
33
A Rare Presentation of Epstein-Barr Virus Infection. 61
31973958 2020
34
New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia. 61
32318071 2020
35
Increasing Incidence and Prevalence of Acquired Hemolytic Anemias in Denmark, 1980-2016. 61
32547241 2020
36
Cold agglutinin disease: where do we stand, and where are we going? 61
32511221 2020
37
A 55-Year-Old Man With Cold Agglutinin Disease. 61
30655006 2020
38
[Autoimmune hemolytic anemias]. 61
32877037 2020
39
Cold reacting anti-M causing delayed hemolytic disease of the newborn. 61
31670408 2019
40
Cryoballoon Ablation Induced Hyperkalemia due to Possible Cold Agglutinin Disease. 61
31391395 2019
41
Serologic response to meningococcal vaccination in patients with cold agglutinin disease (CAD) in the novel era of complement inhibition. 61
31562002 2019
42
A case report of severe nasal ischemia from cold agglutinin disease and a novel treatment protocol including HBOT. 61
31640785 2019
43
Occurrence, thromboembolic risk, and mortality in Danish patients with cold agglutinin disease. 61
31648316 2019
44
Livedo Reticularis in Cold Agglutinin Disease. 61
31553839 2019
45
Cold agglutinin disease and its implications for dental treatment. 61
31120566 2019
46
Abnormal Biodistribution on 99mTc-Red Blood Cell-Labeled Multigated Acquisition in the Presence of Suspected Cold Agglutinin Disease. 61
30700537 2019
47
Defining autoimmune hemolytic anemia: a systematic review of the terminology used for diagnosis and treatment. 61
31235526 2019
48
EBV-related Cold Agglutinin Disease Presenting With Conjugated Hyperbilirubinemia: A Pediatric Case Report and Mini Review. 61
29683945 2019
49
Splenic Marginal Zone B-Cell Lymphoma With Splenic Infarction in a Patient With Cold Agglutinin Disease. 61
30888998 2019
50
High efficacy of eculizumab treatment for fulminant hemolytic anemia in primary cold agglutinin disease. 61
30324459 2019

Variations for Cold Agglutinin Disease

Expression for Cold Agglutinin Disease

Search GEO for disease gene expression data for Cold Agglutinin Disease.

Pathways for Cold Agglutinin Disease

Pathways related to Cold Agglutinin Disease according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 9.9 IL6 CRP

GO Terms for Cold Agglutinin Disease

Biological processes related to Cold Agglutinin Disease according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 positive regulation of T cell proliferation GO:0042102 9.32 IL6 CARD11
2 humoral immune response GO:0006959 9.26 MS4A1 IL6
3 acute-phase response GO:0006953 9.16 IL6 CRP
4 B cell proliferation GO:0042100 8.96 MS4A1 CARD11
5 negative regulation of lipid storage GO:0010888 8.62 IL6 CRP

Sources for Cold Agglutinin Disease

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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