eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Hemolytic-Uremic Syndrome: Differential Diagnoses & Workup

Author: Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine; Consulting Physician, Timmins and District Hospital, Ontario, Canada
Contributor Information and Disclosures

Updated: Dec 5, 2008

Differential Diagnoses

Thrombotic Thrombocytopenic Purpura

Other Problems to Be Considered

Workup

Laboratory Studies

  • Urinalysis
    • Benign mild proteinuria is frequently present.
    • RBCs and RBC casts may be present.
  • Measurement of blood urea nitrogen (BUN), serum creatinine, and serum electrolyte levels
  • Hemoglobin determination
    • Severe anemia may be present.
    • Perform peripheral smear for schistocytes.
    • The degree of thrombocytopenia is not correlated with the severity or the length of hemolytic-uremic syndrome (HUS) illness. The platelet count usually returns to normal within 2 weeks.
    • Determine activated partial thromboplastin time (aPTT), fibrinogen degradation product (FDP), and D-dimer values.
  • Hemolytic workup
    • Results may show anemia.
    • Bilirubin levels may be elevated.
    • Lactic dehydrogenase (LDH) levels may be elevated.
    • Haptoglobin levels may be decreased.
  • Stool culture
    • Obtain a sample for stool culture.
    • Evaluate especially for E coli 0157:H7 and Shigella bacteria.

Imaging Studies

  • Perform renal ultrasonography in patients with renal failure to rule out obstruction.

Procedures

  • Biopsy findings clinically establish the diagnosis of hemolytic-uremic syndrome (HUS). However, kidney biopsy is not required in children. In adults, kidney biopsy is rarely required.
  • Peripheral smears for schistocytes and thrombocytopenia are important.

Histologic Findings

The characteristic pathologic findings of hemolytic-uremic syndrome (HUS) are occlusive lesions of the arterioles and small arteries and consequent tissue microinfarctions.

In hemolytic-uremic syndrome (HUS), the lesions are usually limited to the kidneys, whereas the lesions are more widespread in TTP. Renal lesions are primarily focal and involve both the glomerular capillaries and the afferent arterioles. The venous side of the circulation is usually spared.

A fully developed vascular lesion consists of amorphous-appearing, hyalinelike, thrombi-containing platelet aggregates and a small amount of fibrin that partially or fully occludes the involved small vessels (see Images 1-2). Despite extensive arterial changes, no perivascular cellular infiltration or evidence of associated vasculitis is present. Clinicians may observe subendothelial deposits with overlying endothelial proliferation.

As a rule, changes in renal function and the course of renal failure are well correlated with the pathologic findings in the kidney. Obliterative arteriolar lesions are correlated with hypertension and progressive loss of renal function. Glomerular thrombotic microangiopathic lesions and cortical necrosis are the most frequent histologic findings in Stx-HUS, whereas arterial thrombotic microangiopathic lesions are the most frequent features in non – Stx-HUS.

More on Hemolytic-Uremic Syndrome

Overview: Hemolytic-Uremic Syndrome
Differential Diagnoses & Workup: Hemolytic-Uremic Syndrome
Treatment & Medication: Hemolytic-Uremic Syndrome
Follow-up: Hemolytic-Uremic Syndrome
Multimedia: Hemolytic-Uremic Syndrome
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Siegler RL. Management of hemolytic-uremic syndrome. J Pediatr. Jun 1988;112(6):1014-20. [Medline].

  2. Siegler R, Oakes R. Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr. Apr 2005;17(2):200-4. [Medline].

  3. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. N Engl J Med. Nov 26 1998;339(22):1578-84. [Medline]. [Full Text].

  4. Tsai HM, Lian EC. Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med. Nov 26 1998;339(22):1585-94. [Medline]. [Full Text].

  5. George JN. ADAMTS13, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. Curr Hematol Rep. May 2005;4(3):167-9. [Medline].

  6. Haspel RL, Jarolím P. The "cutting" edge: von Willebrand factor-cleaving protease activity in thrombotic microangiopathies. Transfus Apher Sci. Apr 2005;32(2):177-84. [Medline].

  7. Blackall DP, Marques MB. Hemolytic uremic syndrome revisited: Shiga toxin, factor H, and fibrin generation. Am J Clin Pathol. Jun 2004;121 suppl:S81-8. [Medline].

  8. Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. Mar 19-25 2005;365(9464):1073-86. [Medline].

  9. Caprioli J, Bettinaglio P, Zipfel PF, et al. The molecular basis of familial hemolytic uremic syndrome: mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol. Feb 2001;12(2):297-307. [Medline]. [Full Text].

  10. Fremeaux-Bacchi V, Kemp EJ, Goodship JA, et al. The development of atypical haemolytic-uraemic syndrome is influenced by susceptibility factors in factor H and membrane cofactor protein: evidence from two independent cohorts. J Med Genet. Nov 2005;42(11):852-6. [Medline]. [Full Text].

  11. Edey MM, Mead PA, Saunders RE, et al. Association of a factor H mutation with hemolytic uremic syndrome following a diarrheal illness. Am J Kidney Dis. Mar 2008;51(3):487-90. [Medline].

  12. Lapeyraque AL, Wagner E, Phan V, et al. Efficacy of plasma therapy in atypical hemolytic uremic syndrome with complement factor H mutations. Pediatr Nephrol. Aug 2008;23(8):1363-6. [Medline].

  13. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med. Jun 29 2000;342(26):1930-6. [Medline]. [Full Text].

  14. Cattran DC. Adult hemolytic-uremic syndrome: successful treatment with plasmapheresis. Am J Kidney Dis. Jan 1984;3(4):275-9. [Medline].

  15. Gordon LI, Kwaan HC, Rossi EC. Deleterious effects of platelet transfusions and recovery thrombocytosis in patients with thrombotic microangiopathy. Semin Hematol. Jul 1987;24(3):194-201. [Medline].

  16. Hakim RM, Schulman G, Churchill WH Jr, Lazarus JM. Successful management of thrombocytopenia, microangiopathic anemia, and acute renal failure by plasmapheresis. Am J Kidney Dis. Mar 1985;5(3):170-6. [Medline].

  17. Harkness DR, Byrnes JJ, Lian EC, Williams WD, Hensley GT. Hazard of platelet transfusion in thrombotic thrombocytopenic purpura. JAMA. Oct 23-30 1981;246(17):1931-3. [Medline].

  18. Kwaan HC. Miscellaneous secondary thrombotic microangiopathy. Semin Hematol. Jul 1987;24(3):141-7. [Medline].

  19. Loirat C. Treatment of childhood hemolytic-uremic syndrome with immunoglobulins [abstract]. Pediatr Nephrol. 1991;5:C39.

  20. Loirat C, Baudouin V, Sonsino E, Mariani-Kurdjian P, Elion J. Hemolytic-uremic syndrome in the child. Adv Nephrol Necker Hosp. 1993;22:141-68. [Medline].

  21. Misiani R, Appiani AC, Edefonti A, et al. Haemolytic uraemic syndrome: therapeutic effect of plasma infusion. Br Med J (Clin Res Ed). Nov 6 1982;285(6351):1304-6. [Medline]. [Full Text].

  22. Morel-Maroger L, Kanfer A, Solez K, Sraer JD, Richet G. Prognostic importance of vascular lesions in acute renal failure with microangiopathic hemolytic anemia (hemolytic-uremic syndrome): clinicopathologic study in 20 adults. Kidney Int. May 1979;15(5):548-58. [Medline].

  23. Ponticelli C, Rivolta E, Imbasciati E, Rossi E, Mannucci PM. Hemolytic uremic syndrome in adults. Arch Intern Med. Mar 1980;140(3):353-7. [Medline].

  24. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. Sep 2001;60(3):831-46. [Medline]. [Full Text].

[ CLOSE WINDOW ]

Further Reading

Related eMedicine Topics

[ CLOSE WINDOW ]

Keywords

hemolytic-uremic syndrome, HUS, hemolytic anemia, thrombotic thrombocytopenic purpura, progressive renal failure, microangiopathic hemolytic anemia, renal cortical necrosis, thrombocytopenia, acute renal failure, ARF, TTP, thrombotic microangiopathies, TMAs, verotoxin-producing Escherichia coli, E coli, VTEC, hamburger disease, Gasser syndrome, Shiga-like toxin–associated HUS, Stx-HUS, non–Stx-associated HUS, non–Stx-HUS, Shigella dysenteriae, S dysenteriae

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN, Assistant Professor (VPT), Faculty of Medicine, University of Ottawa; Associate Professor, Department of Internal Medicine, Northern Ontario School of Medicine; Consulting Physician, Timmins and District Hospital, Ontario, Canada
Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, Canadian Medical Association, Ontario Medical Association, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Medical Editor

Rodger L Bick, MD, PhD, FACP, Clinical Professor of Medicine, University of Texas Southwestern Medical Center; Director, Dallas and Pacific Thrombosis Hemostasis and Vascular Medicine Clinical Center
Rodger L Bick, MD, PhD, FACP is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Blood Banks, American Cancer Society, American College of Angiology, American College of Physicians, American Geriatrics Society, American Heart Association, American Medical Association, American Society for Clinical Pathology, American Society of Hematology, Association of Clinical Scientists, California Medical Association, California Thoracic Society, International College of Angiology, International Society of Hematology, International Society on Thrombosis and Haemostasis, New York Academy of Sciences, and Southwest Oncology Group
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

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.

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.

 
 
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.