eMedicine Specialties > Pediatrics: General Medicine > Hematology

Donath-Landsteiner Hemolytic Anemia: Differential Diagnoses & Workup

Author: M Monica Gramatges, MD, Fellow in Pediatric Hematology/Oncology, Stanford University
Coauthor(s): Michael R Jeng, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine
Contributor Information and Disclosures

Updated: May 19, 2009

Differential

Anemia, Acute
Anemia, Chronic
Cold Agglutinin Disease
Evans Syndrome
Lymphoproliferative Disorders
Mononucleosis and Epstein-Barr Virus Infection
Non-Hodgkin Lymphoma
Syphilis
Systemic Lupus Erythematosus

Workup

Laboratory Studies

The following studies are indicated in Donath-Landsteiner hemolytic anemia (DLHA)

  • Hematology
    • Anemia may be mild, moderate, or severe. Anemia is usually normocytic normochromic. However, the mean corpuscular volume (MCV) may be elevated when reticulocytosis is present.
    • Reticulocytopenia is often present in the early stages. Eventually, reticulocytosis develops.
    • Leukopenia may be present early, but the leukocyte count then improves to with the reference range or higher. Leukocytosis may be present during hemolytic episodes.
    • Smear exhibits spherocytosis, polychromasia, nucleated RBCs, anisocytosis, poikilocytosis, and sometimes erythrophagocytosis by neutrophils (see Media files 1-2)8,12  

      Blood smear showing spherocytosis, polychromatoph...

      Blood smear showing spherocytosis, polychromatophilia, and erythrophagocytosis by neutrophils.

      [ CLOSE WINDOW ]
      Blood smear showing spherocytosis, polychromatoph...

      Blood smear showing spherocytosis, polychromatophilia, and erythrophagocytosis by neutrophils.



      Blood smear showing spherocytosis, polychromatoph...

      Blood smear showing spherocytosis, polychromatophilia, and erythrophagocytosis by neutrophils.

      [ CLOSE WINDOW ]
      Blood smear showing spherocytosis, polychromatoph...

      Blood smear showing spherocytosis, polychromatophilia, and erythrophagocytosis by neutrophils.

  • Blood typing
    • Perform blood typing in the event that a blood transfusion is needed.
    • The presence of autoantibodies may interfere with blood typing.
    • The autoantibody may react with the RBCs of all potential donors, making detection of alloantibodies difficult. Compatibility testing can be improved by performing the test at 37°C.
  • Direct antiglobulin test (DAT): This test with anti-IgG produces negative results because of dissociation of IgG from the RBC surface at warm temperatures.
    • DAT may produce positive results if run at a cold temperature.
    • DAT results are positive with anticomplement.
  • Indirect antiglobulin test
    • This must be performed at a cold temperature.
    • Assays using labeled monoclonal anti-immunoglobulin (Ig)G are preferable.
    • The autoantibody is IgG with anti-P specificity, although the specificity may be for other antigens.
    • The titer is usually less than 1:100.
  • Donath-Landsteiner bithermic hemolytic test
    • Positive results are demonstrated by incubation in cold, followed by incubation at 37ºC in the presence of complement.
    • Incubate normal papainized group O RBCs (papainization exposes RBC membrane P -antigen sites) and normal serum (as complement source) with the patient's serum (containing D-L antibody) at 0-4°C.
    • Incubate a second group of samples, as above, at 37°C.
    • Incubate a third group first at 0-4°C for 30 minutes, then at 37°C for 60 minutes.
    • The presence of hemolysis only in the third group constitutes a positive test result and diagnosis of Donath-Landsteiner hemolytic anemia.
    • The Donath-Landsteiner test has a low sensitivity, and results are positive only when the serum antibody titer is high.
    • A false negative test may be seen if the following is present:
      • Low level of antibody from consumption during hemolysis is noted.
      • Low complement levels from consumption during hemolysis is noted.
      • If additional complement is added, presence of globoside in the serum may neutralize the Donath-Landsteiner (D-L) antibody.13
    • Autoantibody specificity may be indicated if D-L test result is positive. Almost all cases are associated with anti-P specificity.
  • Blood chemistry
    • Indirect bilirubin, lactate dehydrogenase, decreased haptoglobin, and plasma hemoglobin levels are elevated, as evidence for hemolysis.
    • BUN and creatinine levels may be elevated if renal insufficiency is present.
    • Complement levels are typically decreased.
  • Urinalysis
    • Hemoglobinuria, methemoglobinuria, and hemosiderinuria are demonstrated.
    • Proteinuria may be present.
  • Serology: Tests results for syphilis, mycoplasmal infection, and viruses (eg, influenza A, measles, mumps, adenovirus, cytomegalovirus, varicella, Epstein-Barr virus [EBV]) may be positive, depending on the underlying cause.

More on Donath-Landsteiner Hemolytic Anemia

Overview: Donath-Landsteiner Hemolytic Anemia
Differential Diagnoses & Workup: Donath-Landsteiner Hemolytic Anemia
Treatment & Medication: Donath-Landsteiner Hemolytic Anemia
Follow-up: Donath-Landsteiner Hemolytic Anemia
Multimedia: Donath-Landsteiner Hemolytic Anemia
References
[ CLOSE WINDOW ]

References

  1. Donath J LK. Uber paroxysmale Hamoglobinurie. Munchener Medizinische Wochenschrift. 1904;51:1590-3.

  2. Bird GW. Paroxysmal cold haemoglobinuria. Br J Haematol. Oct 1977;37(2):167-71. [Medline].

  3. Gehrs BC, Friedberg RC. Autoimmune hemolytic anemia. Am J Hematol. Apr 2002;69(4):258-71. [Medline].

  4. Petz LD. Cold antibody autoimmune hemolytic anemias. Blood Rev. Jan 2008;22(1):1-15. [Medline].

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

  6. 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].

  7. 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].

  8. Heddle NM. Acute paroxysmal cold hemoglobinuria. Transfus Med Rev. Jul 1989;3(3):219-29. [Medline].

  9. Sivakumaran M, Murphy PT, Booker DJ, Wood JK, Stamps R, Sokol RJ. Paroxysmal cold haemoglobinuria caused by non-Hodgkin's lymphoma. Br J Haematol. Apr 1999;105(1):278-9. [Medline].

  10. 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].

  11. 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].

  12. Hernandez JA, Steane SM. Erythrophagocytosis by segmented neutrophils in paroxysmal cold hemoglobinuria. Am J Clin Pathol. Jun 1984;81(6):787-9. [Medline].

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

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

  15. [Guideline] Gibson BE, Todd A, Roberts I, et al. Transfusion guidelines for neonates and older children. Br J Haematol. Feb 2004;124(4):433-53. [Medline]. [Full Text].

  16. 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].

  17. Koppel A, Lim S, Osby M, Garratty G, Goldfinger D. Rituximab as successful therapy in a patient with refractory paroxysmal cold hemoglobinuria. Transfusion. Oct 2007;47(10):1902-4. [Medline].

  18. 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].

  19. Wolach B, Heddle N, Barr RD, Zipursky A, Pai KR, Blajchman MA. Transient Donath-Landsteiner haemolytic anaemia. Br J Haematol. Jul 1981;48(3):425-34. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Donath-Landsteiner hemolytic anemia, Donath-Landsteiner syndrome, paroxysmal cold hemoglobinuria, PCH, cryopathic hemolytic syndrome, cold-induced immune hemolytic anemia, autoimmune hemolytic anemia, AIHA, intravascular hemolysis, anemia, biphasic hemolysin, cold hemolytic syndrome, hemolytic anemia, cold agglutinin disease, hepatosplenomegaly, Raynaud phenomenon, cold urticaria, cyanosis, measles, mumps, Epstein-Barr virus, EBV, cytomegalovirus, CMV, varicella zoster virus, adenovirus, coxsackie A9, parvovirus, influenza A, Mycoplasma pneumoniae, Haemophilus influenza, Klebsiella pneumoniae, Escherichia coli, treatment, diagnosis

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

M Monica Gramatges, MD, Fellow in Pediatric Hematology/Oncology, Stanford University
M Monica Gramatges, MD is a member of the following medical societies: American Association for Cancer Research, American Society of Clinical Oncology, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Coauthor(s)

Michael R Jeng, MD, Associate Professor, Department of Pediatrics, Division of Hematology/Oncology, Stanford University School of Medicine
Michael R Jeng, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, and American Society of Pediatric Hematology/Oncology
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

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.

CME Editor

Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University
Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA, Senior Vice President, Children's National Medical Center (Center for Cancer and Blood Disorders); Director, Center for Cancer and Immunology Research, Children's Research Institute, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University
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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.