Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Cold Agglutinin Disease Medication

  • Author: Salman Abdullah Aljubran, MD; Chief Editor: Michael A Kaliner, MD  more...
 
Updated: Jul 20, 2016
 

Medication Summary

Folic acid supplementation is advisable in individuals with cold agglutinin disease to meet the increased requirements, as a result of hemolytic anemia, for RBC production.

Immunosuppressive and immunomodulating drugs are seldom necessary; however, in cases with underlying malignancies, these agents are required to treat the malignancy. Potent immunosuppression to reduce the production of monoclonal antibody and to reduce/eliminate the abnormal lymphocyte clone has been achieved with cyclophosphamide (1200 mg) and vincristine (2 mg) administered intravenously (IV) on day 1 and prednisone (80 mg/d) administered orally for 5 days, with some beneficial effect in an anecdotal case.[16]

The same patient was treated 10 months later with IV fludarabine (25 mg/m2) daily for 5 days and then every 28 days for 3 courses. Following a third course of treatment, the patient went into remission that lasted for at least 4 years.[16]

Corticosteroids alone may not be routinely useful in patients with cold agglutinin disease, although occasionally a patient may have a clinical response. Patients with mixed cold and warm immune hemolytic anemia are more likely to have a response because of the warm antibody component.

The corticosteroid-sparing agent chlorambucil has also been used to treat cold agglutinin disease.[62]

Rituximab and fludarabine

Rituximab has been widely recognized as being very effective for treating cold agglutinin disease. One study documented a high response rate and durable remissions following therapy using a combination of fludarabine and rituximab. While the results from this study appear positive, extreme caution should be exercised, because the immunosuppressive effects of rituximab superimpose on those of fludarabine.[55]

Bear in mind that one uncommon reported adverse effect of fludarabine is the appearance of a warm autoantibody–induced autoimmune hemolytic anemia. However, according to the authors' experience, persons with Coombs-positive hemolytic anemias have been treated effectively with fludarabine. Responses to interferon alfa therapy have been reported. This therapy may be useful for some B-cell neoplasms.[63]

Cautions

The reader is advised to read the package insert approved by the US Food and Drug Administration (FDA) before using any of the agents listed.

In general, the use of chemotherapeutic agents—which have long-term consequences for the patient and are associated with secondary malignancies, such as leukemias, that are hard to treat—requires very careful decision making in collaboration with a well-informed patient. These agents should be used only for life-threatening, severely symptomatic disease. Therapy also may need to be administered intermittently or infrequently, as the case demands. Tailor therapy to individual needs.

Although alkylating agents have been used in the past and references to these treatments are part of standard texts, the authors suggest that these drugs not be used in patients with cold agglutinin disease, because of the potential for long-term adverse effects from such therapy.

Identifying the proper drug for use in a patient depends on patient characteristics and patient participation in the decision-making process. No guarantees of success can be given with any therapy in cold agglutinin disease.

Next

Immunosuppressants

Class Summary

The metabolites of immunosuppressive alkylating agents cross-link DNA, thereby interfering with cell proliferation. These agents are not needed in patients with idiopathic cold agglutinin disease. Immunosuppressant agents also include antibodies directed against the CD20 antigen found on the surface of B-lymphocytes.

Cyclophosphamide

 

This agent is chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Cystitis can develop with long-term administration, and the leukemogenic potential should be kept in mind. The primary (idiopathic) form of cold agglutinin disease is unlikely to require use of this class of drugs.

Previous
Next

Corticosteroids

Class Summary

These agents elicit anti-inflammatory and immunosuppressive properties, causing profound and varied metabolic effects. They modify the body's immune response to diverse stimuli.

Prednisone

 

This agent is an immunosuppressant used for the treatment of autoimmune or lymphoproliferative disorders. Prednisone modulates lymphocytes and decreases antibody production. It is frequently used with alkylating agents.

Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte activity. It stabilizes lysosomal membranes and suppresses lymphocyte and antibody production. Prednisone may be beneficial in certain cases with low-titer cold agglutinin of high thermal amplitude.

Previous
Next

Immunomodulators

Class Summary

Interferons have had variable success in cold agglutinin–induced hemolytic anemia. Expense and serious adverse effects are issues to consider up front before choosing this class of drug. Interferons are used in the treatment of lymphoproliferative disorders.

Interferon alfa-2b (Intron-A)

 

Interferon alfa is manufactured by recombinant DNA technology. Its mechanism of effect is not clearly understood. However, direct antiproliferative effects against many different kinds of malignant cells have been shown in clinical disease states (eg, lymphoma, melanoma, chronic granulocytic leukemia), and modulation of the host immune response may play an important role.

Previous
Next

Vitamin, Water Soluble

Class Summary

Water-soluble vitamins are necessary for hematopoiesis.

Folic acid (Folacin-800)

 

Folic acid is an important cofactor for enzymes used in the production of RBCs. Chronic hemolytic process requires additional folate.

Previous
Next

Immunosuppressive Agents

Class Summary

Immunosuppressive agents include antibodies that are directed against the CD20 antigen found on the surface of B-lymphocytes.

Rituximab (Rituxan)

 

Effective lowering of IgM and IgG levels is achievable with this anti–B cell antibody. Hypersensitivity reactions can be severe; users of the drug should become completely familiar with the adverse reactions known to occur.

Previous
 
Contributor Information and Disclosures
Author

Salman Abdullah Aljubran, MD Clinical Fellow, Division of Allergy and Immunology, University of South Florida College of Medicine

Salman Abdullah Aljubran, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Allergy, Asthma and Immunology, American Thoracic Society, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Coauthor(s)

Richard F Lockey, MD University Distinguished Health Professor, Professor of Medicine, Pediatrics and Public Health, Joy McCann Culverhouse Chair in Allergy and Immunology, University of South Florida College of Medicine; Director, Division of Allergy and Immunology, James A Haley Veterans’ Hospital

Richard F Lockey, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Allergy Asthma and Immunology, American Association for the Advancement of Science, American College of Occupational and Environmental Medicine, American College of Chest Physicians, American College of Physicians, American Medical Association, Florida Medical Association

Disclosure: Nothing to disclose.

Chief Editor

Michael A Kaliner, MD Clinical Professor of Medicine, George Washington University School of Medicine; Medical Director, Institute for Asthma and Allergy

Michael A Kaliner, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Allergy, Asthma and Immunology, American Society for Clinical Investigation, American Thoracic Society, Association of American Physicians

Disclosure: Nothing to disclose.

Acknowledgements

Nicolas A Camilo, MD Consulting Staff, Mountain States Tumor Institute, Division of Pediatric Hematology-Oncology, St Luke's Regional Medical Center

Disclosure: Nothing to disclose.

Max J Coppes, MD, PhD, MBA Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American Association for Cancer Research, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Gary D Crouch, MD Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

Sharon Georgy, MD Resident Physician, Department of Internal Medicine, University of South Florida College of Medicine

Sharon Georgy, MD is a member of the following medical societies: Phi Beta Kappa

Disclosure: Nothing to disclose.

James L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Gary R Jones, MD Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Jeffrey Lee Kishiyama, MD Assistant Clinical Professor of Medicine, University of California, San Francisco, School of Medicine; Consulting Staff, Allergy and Asthma Associates of Santa Clara Valley Research Center

Disclosure: Nothing to disclose.

Thomas W Loew, MD Director, Clinical Associate Professor of Pediatrics, Pediatric Hematology/Oncology Subspecialty Training Program, University of Iowa Hospitals and Clinics

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Harry L Messmore, Jr, MD Professor, Department of Medicine, Division of Hematology/Oncology, Loyola University Stritch School of Medicine

Harry L Messmore, Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Angiology, American College of Physicians, American Heart Association, American Society of Hematology, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013 Aug 15. 122 (7):1114-21. [Medline]. [Full Text].

  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. [Medline].

  3. Berentsen S, Randen U, Tjønnfjord GE. Cold agglutinin-mediated autoimmune hemolytic anemia. Hematol Oncol Clin North Am. 2015 Jun. 29 (3):455-71. [Medline].

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

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

  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. [Medline].

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

  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. [Medline].

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

  12. Sokol RJ, Hewitt S, Stamps BK. Autoimmune hemolysis: mixed warm and cold antibody type. Acta Haematol. 1983. 69(4):266-74. [Medline].

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

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

  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. [Medline].

  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. [Medline].

  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. [Medline]. [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. [Medline].

  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. [Medline].

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

  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. [Medline]. [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. [Medline]. [Full Text].

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

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

  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. [Medline]. [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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline]. [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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline]. [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. [Medline].

  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. [Medline].

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

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

  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. [Medline].

  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. [Medline].

  47. Schubothe H. The cold hemagglutinin disease. Semin Hematol. 1966 Jan. 3(1):27-47. [Medline].

  48. Hamblin T. Management of cold agglutination syndrome. Transfus Sci. 2000 Feb-Apr. 22(1-2):121-4. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline].

  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. [Medline]. [Full Text].

  53. Webster D, Ritchie B, Mant MJ. Prompt response to rituximab of severe hemolytic anemia with both cold and warm autoantibodies. Am J Hematol. 2004 Apr. 75(4):258-9. [Medline]. [Full Text].

  54. 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. [Medline].

  55. 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. [Medline].

  56. 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. [Medline].

  57. 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. [Medline]. [Full Text].

  58. 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. [Medline].

  59. 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. [Medline].

  60. 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. [Medline].

  61. 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. [Medline].

  62. 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. [Medline]. [Full Text].

  63. O'Connor BM, Clifford JS, Lawrence WD, Logue GL. Alpha-interferon for severe cold agglutinin disease. Ann Intern Med. 1989 Aug 1. 111(3):255-6. [Medline].

 
Previous
Next
 
Peripheral blood smear showing several clumps of RBCs with the largest in the center. These are typical of aggregates seen in persons with cold agglutinin disease.
Blood smear showing spherocytic and agglutinated red blood cells.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.