cold agglutinin syndrome (primary cold agglutinin disease)
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Etiology
- autoimmune (IgM)
- other disorders with IgM kappa monoclonal gammopathy
- disorders with anti-I specificity
- disorders with anti-i specificity
Epidemiology
- 15% of patients with autoimmune hemolytic anemia
- peak incidence of onset: 51-60 years of age
Pathology
- IgM autoantibody binds blood group I/i antigens
- agglutination
- small vessel occlusion
- hemolytic anemia with extravascular hemolysis via complement fixation[2]
- degree of hemolysis depends upon:
- thermal amplitude
- titer
- the higher the titer, the more likely to bind complement
Clinical manifestations
- acrocyanosis of the ears, tip of nose, toes & fingers
- all digits may be equally affected
- skin color is dusky blue, then turns normal or blanches
- NEJM Knowledge+ presents case with normal skin[7]
- jaundice[2]
- hepatomegaly &/or splenomegaly uncommon
- symptoms of anemia: dyspnea, fatigue
Laboratory
- cold agglutinin titer > 1:1000
- direct antiglobulin test
- erythrocyte antibody is IgM
- complement C3d antibody in/on erythrocytes is positive
- optimal temperature for erythrocyte antibody binding is < 37 C[2]
- complete blood count (CBC)
- mild to moderate normocytic anemia
- MCV may be spuriously elevated by agglutination
- peripheral blood smear
- agglutination (erythrocyte clumping rather than stacking <rouleaux>)
- agglutination disappears if smear is prepared at 37 C
- reticulocyte count: reticulocytosis[2]
- can lower hemoglobin A1c[6]
- serum chemistries
- serum lactate dehydrogenase is increased
- bilirubin total in serum is increased
- serum haptoglobin is decreased
- protein electrophoresis with immunofixation
- IgM kappa monoclonal gammopathy may be present
- urinalysis
- urine color: dark
- see ARUP consult[3]
Differential diagnosis
Management
- avoidance of cold temperatures
- warming of infusion
- primary cold agglutinin disease
- rituximab is treatment of choice[2]
- glucocorticoids less effective than in warm autoimmune hemolytic anemia
- splenectomy is generally ineffective
- some patients may respond to immunosuppressive agents
- danazol
- IV immune globulin[2]
- plasmapheresis
- not very effective
- consider if patient is acutely ill because IgM is intravascular
- prognosis: chronic disorder
- specific therapies for specific disorders
More general terms
Additional terms
References
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 415-16
- ↑ Jump up to: 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 Medical Knowledge Self Assessment Program (MKSAP) 14, 16, 17, 18. 19. American College of Physicians, Philadelphia 2006, 2013, 2015, 2018, 2022.
- ↑ Jump up to: 3.0 3.1 ARUP Consult: Cold Agglutinin Disease The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/cold-agglutinin-disease
- ↑ Berentsen S, Tjonnfjord GE. Diagnosis and treatment of cold agglutinin mediated autoimmune hemolytic anemia. Blood Rev. 2012 May;26(3):107-15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22330255
- ↑ Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013 Aug 15;122(7):1114-21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23757733
- ↑ Jump up to: 6.0 6.1 Pant V HbA1c Below the Reportable Range. Lab Med. 2022;53(2):e44-e47. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34611711 https://www.medscape.com/viewarticle/970349
- ↑ Jump up to: 7.0 7.1 NEJM Knowledge+
Berentsen S. How I treat cold agglutinin disease. Blood. 2021 Mar 11;137(10):1295-1303. PMID: https://www.ncbi.nlm.nih.gov/pubmed/33512410 Free article. Review.