eMedicine Specialties > Hematology > Coagulation, Hemostasis, and Disorders

Hemolytic-Uremic Syndrome: Treatment & Medication

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

Treatment

Medical Care

  • Treatment of Stx-HUS: No treatment of proven value has been identified, and comprehensive supportive therapy is still the mainstay during the acute phase.
    • Antibiotics: There is no clear consensus on the use of antibiotics and the evidence supports that antibiotics should be avoided unless patient is septic.
    • Stx-binding agent: Oral administration of SYNSORB PK, which is composed of silicon particles linked to globotriaosylceramide, failed to provide a benefit over placebo.
    • Renal transplantation: This procedure is safe and effective for children who progress to ESRD, with a recurrence rate of 0-10%.
    • Other therapies: Other treatments, including plasma therapy and use of intravenously infused immunoglobulin (IgG), fibrinolytic agents, antiplatelet agents, corticosteroids, and antioxidants were ineffective in controlled clinical trials during the acute phase of the disease.
  • Treatment of non–Stx-HUS
    • Plasma manipulation, exchange versus infusion: The mortality rate decreased from 50% to 25% with the introduction of plasma manipulation, but its efficacy during the acute phase is debated. Plasma exchange might be more effective than infusion, as it removes potentially toxic substances from the circulation. Plasma exchange rather than infusion should be considered first-line therapy in situations that limit the amount of plasma that can be infused, such as renal or heart failure. Plasma treatment should be started within 24 hours of the patient's presentation to decrease treatment failures and then continued once or twice a day for at least 2 days after complete remission. Plasma therapy is contraindicated in S pneumoniae –induced non–Stx-HUS; it may exacerbate the disease because adult plasma contains antibodies against the Thomsen-Friedenreich antigen. A case was recently described showing efficacy of long-term, high-dose plasma infusion (30 mL/kg) at weekly intervals over 30 months, but the long-term effects are still unknown.12
    • Renal transplantation: This procedure is not an option for non–Stx-HUS because of the 50% recurrence rate and >90% rate of graft failure in patients with recurrence. Recurrence rates (30-100%) are significantly higher in patients with HF1 mutations than in those without this mutation. In patients with MCP mutation, outcomes are favorable, and renal transplantation may correct the local MCP dysfunction, as MCP is a membrane-bound protein that is highly expressed in the kidney.
    • Liver transplantation: In patients with HF1 genetic defect, liver transplantation was thought to correct the defect, because HF1 is a plasma protein of liver origin. However, simultaneous liver and kidney transplantation in 2 children were complicated by premature liver failure. At present, this procedure should not be performed unless a patient is at imminent risk for life-threatening complications.
  • Supportive therapy
    • Maintain fluid and electrolyte balance.
    • Adequate blood-pressure control and adequate renin-angiotensin blockade is helpful for patients who have chronic kidney disease after an episode of Stx-HUS.
    • For seizure control, consider prophylactic phenytoin in patients with neurologic symptoms, as 20-40% of patients have seizures.
    • Control azotemia.
    • Optimize nutrition.

Surgical Care

  • Some children with gastrointestinal involvement may require surgery and prolonged parenteral feeding.
  • Splenectomy is used as a last resort in refractory TTP; however, the basis for this treatment is unknown.

Consultations

Patients with hemolytic-uremic syndrome (HUS) may require consultation with the following subspecialists:

  • Nephrologist
  • Hematologist
  • Neurologist in cases of neurologic involvement
  • Intensivists for intensive care unit (ICU) management

Diet

Provide nutritional support during the acute illness. If patients have severe diarrhea, they may require parenteral nutrition. Early restriction of proteins, in addition to renin-angiotensin blockade, may have a beneficial effect on the long-term renal outcome in patients who develop chronic kidney disease after Stx-HUS.

Medication

Clinicians have attempted various treatments for hemolytic-uremic syndrome (HUS) based on different theories.

Antiplatelet Agents

Antiplatelet agents inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, a potent platelet activator.


Aspirin (Bayer Aspirin, Ascriptin, Anacin)

Inhibits prostaglandin synthesis, which prevents platelet-aggregating thromboxane A2 formation, prevents thrombus formation, and shortens thrombocytopenia. Used in combination with plasma exchange because not beneficial alone.

Adult

81-325 mg PO qd

Pediatric

10-15 mg/kg PO qd

Antacids and urinary alkalinizers may decrease the effects; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize the uricosuric effects of probenecid and increase the toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate the glucose-lowering effect of sulfonylurea drugs

Documented hypersensitivity; liver damage, hypoprothrombinemia, vitamin K deficiency, bleeding disorders, asthma; due to association of aspirin with Reye syndrome, do not use in children (<16 y) with flu or in children with febrile illnesses

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause transient decrease in renal function and aggravate chronic kidney disease; avoid in patients with severe anemia, in patients with a history of blood coagulation defects, or in patients taking anticoagulants

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
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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].

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Further Reading

Related eMedicine Topics

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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

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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.

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.

 
 
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