eMedicine Specialties > Hematology > Immune System and Disorders

Hemoglobinuria, Paroxysmal Cold: Treatment & Medication

Author: Corinne Goldberg, MD, Fellow in Transfusion Medicine/Blood Banking, Transfusion Medicine Department, Hoxworth Blood Center, University of Cincinnati
Coauthor(s): Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Contributor Information and Disclosures

Updated: Nov 21, 2008

Treatment

Medical Care

  • The mainstay of treatment for paroxysmal cold hemoglobinuria is supportive care and the avoidance of cold exposure.
  • Administer warmed, packed RBC transfusions for life-threatening hemolysis and symptomatic anemia. Utilizing washed RBC units has not been proven to improve transfusion safety, but this can be performed if patient's condition remains refractory to standard warmed products. As most of the blood supply is P-antigen positive, finding phenotypic p, also called Tj(a-), blood may not be feasible. However, the antibody should not interfere with donor cell survival, nor should it be problematic with pretransfusion and compatibility testing, as the pathogenic immunoresponse does not occur at normal body temperatures. Treat the uncommon chronic form with RBC transfusions only when severe exacerbation occurs.
  • Plasma exchange therapy with 5% albumin fluid replacement has been successfully employed.33 Normal use of plasmapheresis for removal of IgG-induced processes is not as effective due to rebound of immunoglobulin as it shifts from the extravascular to the intravascular compartment. However, due to the low titer and limited production period of the D-L antibody, the process can be effectively controlled. Another theory is that the antibody preferentially binds to the RBC, shifting the antibody equilibrium to the intravascular component, allowing for ease in its removal.39
  • Steroids are commonly employed, but these agents have not been shown to shorten the clinical course of paroxysmal cold hemoglobinuria.
  • Treat underlying secondary conditions with appropriate medical therapy.
  • Hydration, alkalinization of the urine, and other measures may become necessary to prevent renal failure. Symptoms of cold urticaria may be ameliorated by antihistamines.

Surgical Care

Surgery is not indicated in cases of paroxysmal cold hemoglobinuria, other than to aid in the diagnosis of underlying infections or neoplasms.

Consultations

  • A hematologist-oncologist and an infectious diseases expert may be helpful for the proper diagnosis and treatment of paroxysmal cold hemoglobinuria.
  • The family physician, pediatrician, or internist may also consult a nephrologist as needed to assist in the care of affected patients.
  • The support of an experienced laboratory/blood bank is essential for all the serologic testing.

Diet

Folic acid supplements may be useful in the chronic form of paroxysmal cold hemoglobinuria. Encourage patients to eat fresh fruits and vegetables rich in folate.

Activity

Patients with paroxysmal cold hemoglobinuria should limit activities while severely anemic or if complications such as renal insufficiency are present. Avoid activities in the outdoors that are likely to result in cold exposure. Patients with the chronic form of the disease must wear proper clothes and garments to protect the extremities from becoming chilled.

Medication

Currently, there are no pharmaceutical agents available for the treatment of paroxysmal cold hemoglobinuria. 

More on Hemoglobinuria, Paroxysmal Cold

Overview: Hemoglobinuria, Paroxysmal Cold
Differential Diagnoses & Workup: Hemoglobinuria, Paroxysmal Cold
Treatment & Medication: Hemoglobinuria, Paroxysmal Cold
Follow-up: Hemoglobinuria, Paroxysmal Cold
Multimedia: Hemoglobinuria, Paroxysmal Cold
References
Further Reading
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References

  1. Donath J, Landsteiner K. Uber paroxysmale haemoglobinurie. Munchen Medicine Wochenschr. 1904;51:1590-3.

  2. Gottsche B, Salama A, Mueller-Eckhardt C. Donath-Landsteiner autoimmune hemolytic anemia in children. A study of 22 cases. Vox Sang. 1990;58(4):281-6. [Medline].

  3. Eder AF. Review: acute Donath-Landsteiner hemolytic anemia. Immunohematology. 2005;21(2):56-62. [Medline].

  4. Kypson AP, Warner JJ, Telen MJ, Milano CA. Paroxysmal cold hemoglobinuria and cardiopulmonary bypass. Ann Thorac Surg. Feb 2003;75(2):579-81. [Medline].

  5. Bunch C, Schwartz FC, Bird GW. Paroxysmal cold haemoglobinuria following measles immunization. Arch Dis Child. Apr 1972;47(252):299-300. [Medline]. [Full Text].

  6. Taylor CJ, Neilson JR, Chandra D, Ibrahim Z. Recurrent paroxysmal cold haemoglobinuria in a 3-year-old child: a case report. Transfus Med. Oct 2003;13(5):319-21. [Medline].

  7. Sokol RJ, Hewitt S, Stamps BK. Autoimmune haemolysis associated with Donath-Landsteiner antibodies. Acta Haematol. 1982;68(4):268-77. [Medline].

  8. Sokol RJ, Hewitt S, Stamps BK, Hitchen PA. Autoimmune haemolysis in childhood and adolescence. Acta Haematol. 1984;72(4):245-57. [Medline].

  9. Win N, Stamps R, Knight R. Paroxysmal cold haemoglobinuria/Donath-Landsteiner test. Transfus Med. Jun 2005;15(3):254. [Medline].

  10. Vaglio S, Arista MC, Perrone MP, et al. Autoimmune hemolytic anemia in childhood: serologic features in 100 cases. Transfusion. Jan 2007;47(1):50-4. [Medline].

  11. Breccia M, D'Elia GM, Girelli G, et al. Paroxysmal cold haemoglobinuria as a tardive complication of idiopathic myelofibrosis. Eur J Haematol. Oct 2004;73(4):304-6. [Medline].

  12. Papalia MA, Schwarer AP. Paroxysmal cold haemoglobinuria in an adult with chicken pox. Br J Haematol. May 2000;109(2):328-9. [Medline].

  13. Lippman SM, Winn L, Grumet FC, Levitt LJ. Evans' syndrome as a presenting manifestation of atypical paroxysmal cold hemoglobinuria. Am J Med. May 1987;82(5):1065-72. [Medline].

  14. Rosse WF, Hillmen P, Schreiber AD. Immune-mediated hemolytic anemia. Hematology Am Soc Hematol Educ Program. 2004;48-62. [Medline]. [Full Text].

  15. Sharara AI, Hillsley RE, Wax TD, Rosse WF. Paroxysmal cold hemoglobinuria associated with non-Hodgkin's lymphoma. South Med J. Mar 1994;87(3):397-9. [Medline].

  16. Sivakumaran M, Murphy PT, Booker DJ, et al. Paroxysmal cold haemoglobinuria caused by non-Hodgkin's lymphoma. Br J Haematol. Apr 1999;105(1):278-9. [Medline].

  17. Wynn RF, Stevens RF, Bolton-Maggs PH, Schwe K, Will AM. Paroxysmal cold haemoglobinuria of childhood: a review of the management and unusual presenting features of six cases. Clin Lab Haematol. Dec 1998;20(6):373-5. [Medline].

  18. Bell CA, Zwicker H, Rosenbaum DL. Paroxysmal cold hemoglobinuria (P.C.H.) following mycoplasma infection: anti-I specificity of the biphasic hemolysin. Transfusion. May-Jun 1973;13(3):138-41. [Medline].

  19. Rausen AR, LeVine R, Hsu TC, Rosenfield RE. Compatible transfusion therapy for paroxysmal cold hemoglobinuria. Pediatrics. Feb 1975;55(2):275-8. [Medline].

  20. Bird GW, Wingham J, Martin AJ, et al. Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children. J Clin Pathol. Mar 1976;29(3):215-8. [Medline]. [Full Text].

  21. Petz LD, Garratty G. Acquired Immune Hemolytic Anemias. New York, NY: Churchill Livingstone; 1980:37-50.

  22. Dacie J. The Haemolytic Anaemias. 3rd ed. New York, NY: Churchill Livingstone; 1992:210-362.

  23. Gertz MA. Cold hemolytic syndrome. Hematology Am Soc Hematol Educ Program. 2006;19-23. [Medline]. [Full Text].

  24. Ziman A, Hsi R, Goldfinger D. Transfusion Medicine Illustrated: Donath-Landsteiner antibody-associated hemolytic anemia after Haemophilus influenzae infection in a child. Transfusion. Aug 2004;44(8):1127-8. [Medline].

  25. Vergara LH, Mota MC, Sarmento Ada G, Duarte CA, Barbot JM. [Acute renal failure secondary to paroxysmal cold hemoglobinuria] [Spanish]. An Pediatr (Barc). Mar 2006;64(3):267-9. [Medline]. [Full Text].

  26. Sinha A, Richardson G, Patel RT. Cold agglutinin related acrocyanosis and paroxysmal haemolysis. Eur J Vasc Endovasc Surg. Nov 2005;30(5):563-5. [Medline].

  27. Chrobak L. Paroxysmal nocturnal hemoglobinuria (membrane defect, pathogenesis, aplastic anemia, diagnosis). Acta Medica (Hradec Kralove). 2000;43(1):3-8. [Medline].

  28. Prasad AS, Berman L, Tranchida L, Poulok MD. Red cell hypoplasia, cold hemoglobinuria and M-type gamma G serum paraprotein and Bence Jones proteinuria in a patient with lymphoproliferative disorder. Blood. Feb 1968;31(2):151-65. [Medline]. [Full Text].

  29. Subbarayan PR, Shichishima T, Yoshida H, Maruyama Y, Naiki M. Report on a patient with paroxysmal cold hemoglobinuria. Int J Hematol. Feb 1997;65(2):165-7. [Medline].

  30. Chen R, Nagarajan S, Prince GM, et al. Impaired growth and elevated fas receptor expression in PIGA(+) stem cells in primary paroxysmal nocturnal hemoglobinuria. J Clin Invest. Sep 2000;106(5):689-96. [Medline]. [Full Text].

  31. Brodsky RA, Mukhina GL, Li S, et al. Improved detection and characterization of paroxysmal nocturnal hemoglobinuria using fluorescent aerolysin. Am J Clin Pathol. Sep 2000;114(3):459-66. [Medline].

  32. Garratty G. Erythrophagocytosis on the peripheral blood smear and paroxysmal cold hemoglobinuria. Transfusion. Aug 2001;41(8):1073-4. [Medline].

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

  34. Mukhopadhyay S, Keating L, Souid AK. Erythrophagocytosis in paroxysmal cold hemoglobinuria. Am J Hematol. Nov 2003;74(3):196-7. [Medline]. [Full Text].

  35. Nordhagen R, Stensvold K, Winsnes A, Skyberg D, Storen A. Paroxysmal cold haemoglobinuria. The most frequent acute autoimmune haemolytic anaemia in children?. Acta Paediatr Scand. Mar 1984;73(2):258-62. [Medline].

  36. Lindgren S, Zimmerman S, Gibbs F, Garratty G. An unusual Donath-Landsteiner antibody detectable at 37 degrees C by the antiglobulin test. Transfusion. Mar-Apr 1985;25(2):142-4. [Medline].

  37. Nordhagen R. Two cases of paroxysmal cold hemoglobinuria with a Donath-Landsteiner antibody reactive by the indirect antiglobulin test using anti-IgG. Transfusion. Feb 1991;31(2):190-1. [Medline].

  38. Thomas AT. Autoimmune hemolytic anemias. In: Lee GR, Foerster J, Lukens J, et al, eds. Wintrobe's Clinical Hematology. 10th ed. Baltimore, Md: Williams & Wilkins; 1999:1233-63.

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

  40. Hothi DK, Bass P, Morgan M, et al. Acute renal failure in a patient with paroxysmal cold hemoglobinuria. Pediatr Nephrol. Apr 2007;22(4):593-6. [Medline].

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Further Reading

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Keywords

paroxysmal cold hemoglobinuria, hemolytic anemia, myelodysplastic syndromes, Donath-Landsteiner hemolytic anemia, cold-induced immune hemolytic anemia, PCH, paroxysmal nocturnal hemoglobinuria, autoimmune hemolytic anemia, Marchiafava-Micheli syndrome, AIHA, intravascular hemolysis, anemia, blood disorder, blood disease, cold exposure, biphasic hemolysin, hematologic disorders, syphilis, measles, mumps, influenza, varicella-zoster virus, VZV, cytomegalovirus, CMV, Epstein-Barr virus, EBV, adenovirus, parvovirus B19, Coxsackie A9, , , , , ,

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Contributor Information and Disclosures

Author

Corinne Goldberg, MD, Fellow in Transfusion Medicine/Blood Banking, Transfusion Medicine Department, Hoxworth Blood Center, University of Cincinnati
Disclosure: Nothing to disclose.

Coauthor(s)

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

Medical Editor

Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University Medical College; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Hematology, International Society on Thrombosis and Haemostasis, and New York Academy of Sciences
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald A Sacher, MB, BCh, MD, FRCPC, Professor, Internal Medicine and Pathology, Director, Hoxworth Blood Center, University of Cincinnati Academic Health Center
Ronald A Sacher, MB, BCh, MD, FRCPC is a member of the following medical societies: American Society of Hematology
Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

Emmanuel C Besa, MD, Professor, Department of Medicine, Division of Hematologic Malignancies, Kimmel Cancer Center, Thomas Jefferson University
Emmanuel C Besa, MD is a member of the following medical societies: American Association for Cancer Education, American College of Clinical Pharmacology, American Federation for Medical Research, American Society of Hematology, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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