cold agglutinin syndrome (primary cold agglutinin disease)
Jump to navigation
Jump to search
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
- serum calcium normal (elevated serum calcium in multiple myeloma*)
- protein electrophoresis with immunofixation
- IgM kappa monoclonal gammopathy may be present
- urinalysis
- urine color: dark
- see ARUP consult[3]
* serum calcium distinguishes etiology of rouleaux
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
- ↑ 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.
Medical Knowledge Self Assessment Program (MKSAP) 20 American College of Physicians, Philadelphia 2025 - ↑ 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://pubmed.ncbi.nlm.nih.gov/22330255
- ↑ Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013 Aug 15;122(7):1114-21 PMID: https://pubmed.ncbi.nlm.nih.gov/23757733
- ↑ 6.0 6.1 Pant V HbA1c Below the Reportable Range. Lab Med. 2022;53(2):e44-e47. PMID: https://pubmed.ncbi.nlm.nih.gov/34611711 https://www.medscape.com/viewarticle/970349
- ↑ 7.0 7.1 NEJM Knowledge+
Berentsen S. How I treat cold agglutinin disease. Blood. 2021 Mar 11;137(10):1295-1303. PMID: https://pubmed.ncbi.nlm.nih.gov/33512410 Free article. Review.