Hemolytic-Uremic Syndrome Clinical Presentation

  • Author: Malvinder S Parmar, MB, MS, FRCP(C), FACP, FASN; Chief Editor: Emmanuel C Besa, MD   more...
 
Updated: Aug 26, 2010
 

History

History findings may include the following:

  • Prodromal gastroenteritis (83%) - Prodrome of fever (56%), bloody diarrhea (50%) for 2-7 days before the onset of renal failure
  • Irritability, lethargy
  • Seizures (20%)
  • Acute renal failure (97%)
  • Anuria (55%)
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Physical

Physical findings may include the following:

  • Hypertension (47%)
  • Edema, fluid overload (69%)
  • Pallor, often severe
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Causes

Hemolytic-uremic syndrome (HUS) predominantly occurs in infants and children after prodromal diarrhea. In summer epidemics, the disease may be related to infectious causes.

Bacterial infections may include the following:

  • S dysenteriae
  • E coli
  • Salmonella typhi
  • Campylobacter jejuni
  • Yersinia pseudotuberculosis
  • Neisseria meningitidis
  • S pneumoniae
  • Legionella pneumophila
  • Mycoplasma species

Rickettsial infections may include Rocky Mountain spotted fever and microtatobiotes

Viral infections may include the following:

  • Human immunodeficiency virus (HIV)
  • Coxsackievirus
  • Echovirus
  • Influenza virus
  • Epstein-Barr virus
  • Herpes simplex virus

Fungal infections can include Aspergillus fumigatus.

Vaccinations may include the following:

  • Influenza triple-antigen vaccine
  • Typhoid-paratyphoid A and B (TAB) vaccine
  • Polio vaccine

Causes of the secondary or sporadic form may include the following:

  • Pregnancy and puerperium
  • Oral contraception
  • Cancers (chiefly mucin-producing adenocarcinomas)
  • Chemotherapeutic agents (mitomycin-C, cisplatin, bleomycin, gemcitabine)
  • Immunotherapeutic agents (cyclosporine, tacrolimus, OKT3, interferon [IFN])
  • Antiplatelet agents (ticlopidine, clopidogrel)
  • Malignant hypertension
  • Collagen vascular disorder (eg, SLE)
  • Primary glomerulopathies
  • Transplantation (eg, of kidney, bone marrow): This can be de novo or recurrent. It occurs in 5-15% of renal transplant patients who receive cyclosporine and in about 1% of patients who receive tacrolimus.

An immunodeficiency-related cause includes thymic dysplasia.

Familial causes account for 3% of all cases of hemolytic-uremic syndrome (HUS), and both autosomal dominant and autosomal recessive forms of inheritance have been reported. Autosomal recessive HUS occurs in childhood, and patients have a poor prognosis with frequent recurrences and a mortality rate of 60-70%. Autosomal dominant HUS occurs mostly in adults, who have a poor prognosis; the cumulative incidence of death or ESRD is 50-90%.

No cause is identified in about 50% of all cases of sporadic non–Stx HUS.

Drugs implicated in causing non–Stx-HUS are as follows:

  • Anticancer agents: These include mitomycin, cisplatin, bleomycin, and gemcitabine. The risk for hemolytic-uremic syndrome (HUS) after mitomycin therapy is 2-10%, and onset may be delayed, occurring almost 1 year after the patient starts treatment. The prognosis is poor, with a 75% mortality rate at 4 months.
  • Immunotherapeutic agents: Examples are cyclosporine, tacrolimus, OKT3, and IFN.
  • Antiplatelet agents: Examples are ticlopidine and clopidogrel.
  • Posttransplantation hemolytic-uremic syndrome (HUS) is reported with increasing frequency and may be primary (de novo) or recurrent. It is often a consequence of the use of calcineurin inhibitors or of humoral (C4b positive) rejection. This condition occurs in 5-15% of renal transplant patients treated with cyclosporine and in about 1% of patients treated with tacrolimus.

Pregnancy-associated hemolytic-uremic syndrome (HUS) occasionally develops as a complication of preeclampsia. Patients may progress to full-blown hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Postpartum HUS usually occurs within 3 months of delivery. The prognosis is poor, with a 50-60% mortality rate, and residual renal dysfunction and hypertension occur in most patients.

Idiopathic hemolytic-uremic syndrome (HUS) accounts for 50% of all cases of sporadic non – Stx-HUS.

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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.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

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 Association for the Advancement of Science, American Association of Blood Banks, American Clinical and Climatological Association, American Society for Clinical Pathology, American Society of Hematology, College of American Pathologists, International Society of Blood Transfusion, International Society on Thrombosis and Haemostasis, and Royal College of Physicians and Surgeons of Canada

Disclosure: Glaxo Smith Kline Honoraria Speaking and teaching; Talecris Honoraria Board membership

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 Clinical Oncology, American Society of Hematology, and New York Academy of Sciences

Disclosure: Nothing to disclose.

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, Dragon-Durey MA, Strain L, Loirat C, 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. McGannon CM, Fuller CA, Weiss AA. Different classes of antibiotics differentially influence Shiga toxin production. Antimicrob Agents Chemother. Sept 2010;54(9):3790-3798.

  14. 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].

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

  16. 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].

  17. 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].

  18. 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].

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

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

  21. 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].

  22. Misiani R, Appiani AC, Edefonti A, Gotti E, Bettinelli A, Giani M, 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].

  23. 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].

  24. 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].

  25. 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].

 
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Photomicrograph (hematoxylin and eosin, original magnification ×25) shows diffuse thickening of the glomerular capillary wall with double contouring (arrow) and swelling of endothelial cells. Fibrin thrombi and packed red blood cells are visible in the lumina (arrowhead). Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
Photomicrograph (periodic acid-Schiff, original magnification ×40) shows diffuse thickening of the glomerular capillary wall with double contouring (arrow) and swelling of endothelial cells. Courtesy of Madeleine Moussa, MD, FRCPC, Department of Pathology, London Health Sciences Centre, London, Ontario, Canada.
 
 
 
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