Cold Agglutinin Disease Questions & Answers

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2. Małecka A, Trøen G, Tierens A, Østlie I, Małecki J, Randen U, et al. Immunoglobulin heavy and light chain gene features are correlated with primary cold agglutinin disease onset and activity. Haematologica. 2016 May 19. [QxMD MEDLINE Link].

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4. Rosse WF, Adams JP. The variability of hemolysis in the cold agglutinin syndrome. Blood. 1980 Sep. 56(3):409-16. [QxMD MEDLINE Link]. [Full Text].

5. Dacie J, The auto-immune haemolytic anaemias. The Haemolytic Anaemias. 3rd ed. Edinburgh, United Kingdom: Churchill Livingstone; 1992. Vol 3.: 210-362.

6. Harboe M, van Furth R, Schubothe H, Lind K, Evans RS. Exclusive occurrence of K chains in isolated cold haemagglutinins. Scand J Haematol. 1965. 2(3):259-66. [QxMD MEDLINE Link].

7. Angevine CD, Andersen BR, Barnett EV. A cold agglutinin of the IgA class. J Immunol. 1966 Apr. 96(4):578-86. [QxMD MEDLINE Link].

8. Garratty G, Petz LD, Hoops JK. The correlation of cold agglutinin titrations in saline and albumin with haemolytic anaemia. Br J Haematol. 1977 Apr. 35(4):587-95. [QxMD MEDLINE Link].

9. Wortman J, Rosse W, Logue G. Cold agglutinin autoimmune hemolytic anemia in nonhematologic malignancies. Am J Hematol. 1979. 6(3):275-83. [QxMD MEDLINE Link].

10. Roelcke D. The Lud cold agglutinin: a further antibody recognizing N-acetylneuraminic acid-determined antigens not fully expressed at birth. Vox Sang. 1981 Nov-Dec. 41(5-6):316-8. [QxMD MEDLINE Link].

11. Crisp D, Pruzanski W. B-cell neoplasms with homogeneous cold-reacting antibodies (cold agglutinins). Am J Med. 1982 Jun. 72(6):915-22. [QxMD MEDLINE Link].

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13. Roelcke D. Reaction of anti-Gd, anti-Fl and anti-Sa cold agglutinins with p erythrocytes. Vox Sang. 1984. 46(3):161-4. [QxMD MEDLINE Link].

14. Agarwal SK, Ghosh PK, Gupta D. Cardiac surgery and cold-reactive proteins. Ann Thorac Surg. 1995 Oct. 60(4):1143-50. [QxMD MEDLINE Link].

15. Packman CH, Leddy JP. Cryopathic hemolytic syndromes. Beutler E, Lichtman M, Coller B, Kippst, eds. Williams Hematology. 5th ed. New York, NY: McGraw-Hill; 1995. 685-91.

16. Jacobs A. Cold agglutinin hemolysis responding to fludarabine therapy. Am J Hematol. 1996 Dec. 53(4):279-80. [QxMD MEDLINE Link].

17. Terness P, Kirschfink M, Navolan D, et al. Inverse correlation between IgG-antihinge region and antierythrocyte autoantibody in chronic benign and malignant cold agglutination. J Clin Immunol. 1997 May. 17(3):220-7. [QxMD MEDLINE Link].

18. Thorpe SJ, Turner CE, Stevenson FK, et al. Human monoclonal antibodies encoded by the V4-34 gene segment show cold agglutinin activity and variable multireactivity which correlates with the predicted charge of the heavy-chain variable region. Immunology. 1998 Jan. 93(1):129-36. [QxMD MEDLINE Link]. [Full Text].

19. Ciejka JZ, Cook EB, Lawler D, et al. Severe cold agglutinin disease and cryoglobulinemia secondary to a monoclonal anti-Pr2 IgM lambda cryoagglutinin. Clin Exp Rheumatol. 1999 Mar-Apr. 17(2):227-31. [QxMD MEDLINE Link].

20. De Silva BD, McLaren K, Doherty VR. Equestrian perniosis associated with cold agglutinins: a novel finding. Clin Exp Dermatol. 2000 Jun. 25(4):285-8. [QxMD MEDLINE Link].

21. Potter KN. Molecular characterization of cold agglutinins. Transfus Sci. 2000 Feb-Apr. 22(1-2):113-9. [QxMD MEDLINE Link].

22. Jefferies LC, Carchidi CM, Silberstein LE. Naturally occurring anti-i/I cold agglutinins may be encoded by different VH3 genes as well as the VH4.21 gene segment. J Clin Invest. 1993 Dec. 92(6):2821-33. [QxMD MEDLINE Link]. [Full Text].

23. Berentsen S, Beiske K, Tjonnfjord GE. Primary chronic cold agglutinin disease: an update on pathogenesis, clinical features and therapy. Hematology. 2007 Oct. 12(5):361-70. [QxMD MEDLINE Link]. [Full Text].

24. Gertz MA. Management of cold haemolytic syndrome. Br J Haematol. 2007 Aug. 138(4):422-9. [QxMD MEDLINE Link].

25. McNicholl FP. Clinical syndromes associated with cold agglutinins. Transfus Sci. 2000 Feb-Apr. 22(1-2):125-33. [QxMD MEDLINE Link].

26. Maniatis A, Papayannopoulou T, Bertles JF. Fetal characteristics of erythrocytes in sickle cell anemia: an immunofluorescence study of individual cells. Blood. 1979 Jul. 54(1):159-68. [QxMD MEDLINE Link]. [Full Text].

27. Sokol RJ, Booker DJ, Stamps R. Erythropoiesis: Paroxysmal Cold Haemoglobinuria: A Clinico-Pathological Study of Patients with a Positive Donath-Landsteiner Test. Hematology. 1999. 4 (2):137-164. [QxMD MEDLINE Link].

28. Sokol RJ, Booker DJ, Stamps R, Walewska R. Cold haemagglutinin disease: clinical significance of serum haemolysins. Clin Lab Haematol. 2000 Dec. 22(6):337-44. [QxMD MEDLINE Link].

29. Maura F, Visco C, Falisi E, Reda G, Fabris S, Agnelli L, et al. B-cell receptor configuration and adverse cytogenetics are associated with autoimmune hemolytic anemia in chronic lymphocytic leukemia. Am J Hematol. 2012 Sep 26. [QxMD MEDLINE Link].

30. Khan FY, A yassin M. Mycoplasma pneumoniae associated with severe autoimmune hemolytic anemia: case report and literature review. Braz J Infect Dis. 2009 Feb. 13(1):77-9. [QxMD MEDLINE Link].

31. Delval A, Stojkovic T, Vermersch P. Relapsing sensorimotor neuropathy with ophthalmoplegia, antidisialosyl antibodies, and extramembranous glomerulonephritis. Muscle Nerve. 2006 Feb. 33(2):274-7. [QxMD MEDLINE Link].

32. Siddiqui K, Cahalane E, Keogan M, Hardiman O. Chronic ataxic neuropathy with cold agglutinins: atypical phenotype and response to anti-CD20 antibodies. Neurology. 2003 Nov 11. 61(9):1307-8. [QxMD MEDLINE Link].

33. Skorupa A, Chaudhary UB, Lazarchick J. Cold agglutinin induced autoimmune hemolytic anemia and NK-cell leukemia: a new association. Am J Hematol. 2007 Jul. 82(7):668-71. [QxMD MEDLINE Link]. [Full Text].

34. Cao L, Kaiser P, Gustin D, Hoffman R, Feldman L. Cold agglutinin disease in a patient with uterine sarcoma. Am J Med Sci. 2000 Nov. 320(5):352-4. [QxMD MEDLINE Link].

35. Michaux L, Dierlamm J, Wlodarska L, et al. Trisomy 3q11-q29 is recurrently observed in B-cell non-Hodgkin's lymphomas associated with cold agglutinin syndrome. Ann Hematol. 1998 May. 76(5):201-4. [QxMD MEDLINE Link].

36. Chng WJ, Chen J, Lim S, et al. Translocation (8;22) in cold agglutinin disease associated with B-cell lymphoma. Cancer Genet Cytogenet. 2004 Jul 1. 152(1):66-9. [QxMD MEDLINE Link].

37. Kitamura T, Mizuta K, Kawarasaki H, Sugawara Y, Makuuchi M. Severe hemolytic anemia related to production of cold agglutinins following living donor liver transplantation: a case report. Transplant Proc. 2003 Feb. 35(1):399-400. [QxMD MEDLINE Link].

38. Tamura T, Kanamori H, Yamazaki E, et al. Cold agglutinin disease following allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Mar. 13(3):321-3. [QxMD MEDLINE Link].

39. Thomson AW, Bonham CA, Zeevi A. Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Ther Drug Monit. 1995 Dec. 17(6):584-91. [QxMD MEDLINE Link].

40. Oshima M, Maeda H, Morimoto K, Doi M, Kuwabara M. Low-titer cold agglutinin disease with systemic sclerosis. Intern Med. 2004 Feb. 43(2):139-42. [QxMD MEDLINE Link]. [Full Text].

41. Torres JR, Villegas L, Perez H, et al. Low-grade parasitaemias and cold agglutinins in patients with hyper-reactive malarious splenomegaly and acute haemolysis. Ann Trop Med Parasitol. 2003 Mar. 97(2):125-30. [QxMD MEDLINE Link].

42. Johnson ST, McFarland JG, Kelly KJ, Casper JT, Gottschall JL. Transfusion support with RBCs from an Mk homozygote in a case of autoimmune hemolytic anemia following diphtheria-pertussis-tetanus vaccination. Transfusion. 2002 May. 42(5):567-71. [QxMD MEDLINE Link].

43. Gunduz Gedikoglu A, Cantez T. Haemolytic-anaemia relapses after immunisation and pertussis. Lancet. 1967 Oct 21. 2(7521):894-5. [QxMD MEDLINE Link].

44. Zupanska B, Lawkowicz W, Gorska B, et al. Autoimmune haemolytic anaemia in children. Br J Haematol. 1976 Nov. 34(3):511-20. [QxMD MEDLINE Link].

45. Haneberg B, Matre R, Winsnes R, et al. Acute hemolytic anemia related to diphtheria-pertussis-tetanus vaccination. Acta Paediatr Scand. 1978 May. 67(3):345-50. [QxMD MEDLINE Link].

46. Kamesaki T, Toyotsuji T, Kajii E. Characterization of direct antiglobulin test-negative autoimmune hemolytic anemia: A study of 154 cases. Am J Hematol. 2012 Oct 25. [QxMD MEDLINE Link].

47. Berentsen S. How I treat cold agglutinin disease. Blood. 2021 Mar 11. 137 (10):1295-1303. [QxMD MEDLINE Link]. [Full Text].

48. Berentsen S. New Insights in the Pathogenesis and Therapy of Cold Agglutinin-Mediated Autoimmune Hemolytic Anemia. Front Immunol. 2020. 11:590. [QxMD MEDLINE Link]. [Full Text].

49. Hoppe B, Gaedicke G, Kiesewetter H, Salama AR. Response to intravenous immunoglobulin G in an infant with immunoglobulin A-associated autoimmune haemolytic anaemia. Vox Sang. 2004 Feb. 86(2):151-3. [QxMD MEDLINE Link].

50. Roy-Burman A, Glader BE. Resolution of severe Donath-Landsteiner autoimmune hemolytic anemia temporally associated with institution of plasmapheresis. Crit Care Med. 2002 Apr. 30(4):931-4. [QxMD MEDLINE Link].

51. Teachey DT, Felix CA. Development of cold agglutinin autoimmune hemolytic anemia during treatment for pediatric acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2005 Jul. 27(7):397-9. [QxMD MEDLINE Link].

52. Giulino LB, Bussel JB, Neufeld EJ. Treatment with rituximab in benign and malignant hematologic disorders in children. J Pediatr. 2007 Apr. 150(4):338-44, 344.e1. [QxMD MEDLINE Link]. [Full Text].

53. Berentsen S, Ulvestad E, Tjonnfjord GE. B-lymphocytes as targets for therapy in chronic cold agglutinin disease. Cardiovasc Hematol Disord Drug Targets. 2007 Sep. 7(3):219-27. [QxMD MEDLINE Link].

54. Berentsen S, Randen U, Vagan AM, Hjorth-Hansen H, Vik A, Dalgaard J. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28. 116(17):3180-4. [QxMD MEDLINE Link].

55. Berentsen S, Randen U, Oksman M, Birgens H, Tvedt THA, Dalgaard J, et al. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017 Jul 27. 130 (4):537-541. [QxMD MEDLINE Link].

56. Jäger U, Barcellini W, Broome CM, Gertz MA, Hill A, Hill QA, et al. Diagnosis and treatment of autoimmune hemolytic anemia in adults: Recommendations from the First International Consensus Meeting. Blood Rev. 2020 May. 41:100648. [QxMD MEDLINE Link].

57. Sandip Panicker, Graham C. Parry, Michael Fillitz, et al. TNT009, a monoclonal antibody inhibitor of C1s, induces a rapid and complete remission of anemia in primary cold agglutinin disease patients. Immunobiology. 2016 Oct 01. 221:1170-1171.

58. Röth A, Barcellini W, D'Sa S, et al. Inhibition of Complement C1s with Sutimlimab in Patients with Cold Agglutinin Disease (CAD): Results from the Phase 3 Cardinal Study. Blood. 2019. 134 (Supplement_2):LBA-2. [Full Text].

59. Röth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, et al. Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8. 384 (14):1323-1334. [QxMD MEDLINE Link]. [Full Text].

60. Gelbenegger G, Schoergenhofer C, Derhaschnig U, Buchtele N, Sillaber C, Fillitz M, et al. Inhibition of complement C1s in patients with cold agglutinin disease: lessons learned from a named patient program. Blood Adv. 2020 Mar 24. 4 (6):997-1005. [QxMD MEDLINE Link]. [Full Text].

61. Shapiro R, Chin-Yee I, Lam S. Eculizumab as a bridge to immunosuppressive therapy in severe cold agglutinin disease of anti-Pr specificity. Clin Case Rep. 2015 Nov. 3 (11):942-4. [QxMD MEDLINE Link].

62. Alexander Röth, Martin Bommer, Andreas Hüttmann, et al. Complement Inhibition with Eculizumab in Patients with Cold Agglutinin Disease (CAD): Results from a Prospective Phase II Trial (DECADE Trial). Blood. 2015 Dec 06. 126:274.

63. Inaba H, Geiger TL, Lasater OE, Wang WC. A case of hemoglobin SC disease with cold agglutinin-induced hemolysis. Am J Hematol. 2005 Jan. 78(1):37-40. [QxMD MEDLINE Link]. [Full Text].

64. Batalias L, Trakakis E, Loghis C, et al. Autoimmune hemolytic anemia caused by cold agglutinins in a young pregnant woman. J Matern Fetal Neonatal Med. 2006 Apr. 19(4):251-3. [QxMD MEDLINE Link].

65. Atkinson VP, Soeding P, Horne G, Tatoulis J. Cold agglutinins in cardiac surgery: management of myocardial protection and cardiopulmonary bypass. Ann Thorac Surg. 2008 Jan. 85(1):310-1. [QxMD MEDLINE Link].

66. Aoki A, Kay GL, Zubiate P, Ruggio J, Kay JH. Cardiac operation without hypothermia for the patient with cold agglutinin. Chest. 1993 Nov. 104(5):1627-9. [QxMD MEDLINE Link].

67. Barbara DW, Mauermann WJ, Neal JR, Abel MD, Schaff HV, Winters JL. Cold agglutinins in patients undergoing cardiac surgery requiring cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2013 Sep. 146(3):668-80. [QxMD MEDLINE Link].

68. Hippe E, Jensen KB, Olesen H, Lind K, Thomsen PE. Chlorambucil treatment of patients with cold agglutinin syndrome. Blood. 1970 Jan. 35(1):68-72. [QxMD MEDLINE Link]. [Full Text].

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James Carson Collie, MD Resident Physician, Department of Internal Medicine, University of South Florida Morsani College of Medicine

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