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Hemolytic Uremic Syndrome Treatment & Management

  • Author: Robert Stanley Rust, Jr, MD, MA; Chief Editor: Amy Kao, MD  more...
 
Updated: Dec 17, 2013
 

Medical Care

Management of HUS is supportive and chiefly involves dialysis for individuals with renal failure. Acute medical issues involve the management of renal failure and hypertension, the maintenance of fluid status in the face of renal failure, and the treatment of fever and catabolic status. Adult HUS and its underlying illnesses respond poorly to various forms of medical therapy.

Among the therapeutic options considered in adults are anticoagulation; antiplatelet or antioxidant agents; fibrinolytics; thrombolysis (with streptokinase); plasmapheresis and plasma exchange; and infusions of plasma, prostacyclin, or gamma globulin.[65, 66, 67] None of these approaches has been proven effective beyond excellent supportive care. Plasma manipulations do not appear to have the same degree of benefit in HUS as such manipulations have shown in TTP.[68] Among other forms of therapy that have been tried in adults, prednisone, azathioprine, vincristine, and intravenous immunoglobulin (IVIg) are the medications for which the evidence of efficacy is strongest.

Eculizumab

Eculizumab (Soliris) is the first treatment approved by the US Food and Drug Administration (FDA) (September, 2011) for adults and children with atypical hemolytic uremic syndrome (aHUS). Approval was based on data from adults and children who were resistant or intolerant to, or receiving, long-term plasma exchange/infusion. Data also included children (aged 2 mo to 17 y) who received eculizumab with or without prior plasma exchange/infusion. Eculizumab demonstrated significant improvement in platelet count from baseline (P = .0001). Thrombotic microangiopathy events were reduced, and maintained or improved kidney function was also reported.[69, 71, 72, 73]

Antibiotics

The value of antibiotics has been debated. Antibiotics may be required where sepsis or lung infections complicate HUS, as in HUS associated with S pneumoniae infection. In 1 study, antibiotic treatment in the acute enteric stage of E coli enteritis increased the risk for HUS 17-fold.[36] A meta-analysis did not show such an effect. In 1 adult with E coli O157:H7 bacteremia and urinary tract infection who developed HUS, both renal and hematologic abnormalities promptly improved with antibiotic treatment. Antibiotics may be lifesaving in patients with S dysenteriae –related HUS if started early enough. The treatment of sepsis associated with S pneumoniae HUS is similarly important.

Transfusion

Blood transfusion is required in as many as 70-90% of children with postinfectious HUS, particularly those with hemorrhagic colitis. Platelet transfusion is necessary in about 30% of children with HUS.

Although some regard platelet transfusions as dangerous in TTP, as many as 30% of patients with HUS receive platelet transfusions in addition to other supportive therapies.

Management of blood pressure

Blood pressure support is required for individuals who develop septic shock. Shock occurs in more than 30% of individuals with S dysenteriae –related HUS and in some patients with sepsis due to S pneumoniae –related HUS.

Arterial hypertension develops in two thirds of patients and is often severe. Arterial hypertension may lead to cardiac failure and pulmonary edema.

Management with antihypertensives may be important in the management of HUS-associated posterior leukoencephalopathy.

Plasma treatment

Plasma administration and manipulations appear to be less beneficial in HUS than in TTP.

Plasma treatment has been particularly advocated in HIV-associated HUS and in HUS occurring as a postpartum complication. It has been used in sporadic idiopathic non–Stx-HUS; HUS as a complication of antineoplastic, antiplatelet, or immunosuppressive drugs; and in sporadic or familial HUS associated with abnormalities of complement pathway regulatory proteins, such as factor H, membrane cofactor protein (MCP), and factor I.

Anticoagulation

Anticoagulation, which is sometimes attempted in adults with HUS, entails risk in children because childhood HUS is frequently complicated by both bleeding and hypertension. Where tried, anticoagulation does not appear to be beneficial, even when combined with oral antiplatelet agents. Indeed, heparin therapy may significantly increase mortality;[74, 75] therefore, this approach is probably contraindicated.

Adsorption

Investigations have been undertaken to evaluate the effectiveness of administering preparations containing inert adsorptive surfaces that can bind circulating verocytotoxin and thereby prevent their attachment to endothelial surfaces, where they can cause injury. SYNSORB-pk ingestion was among the first approaches tried.[21] Despite initial enthusiasm, this approach appears to have been abandoned. Other similar preparations have also been evaluated, but none have been effective.[76]

About one third of patients become anuric. In combination with their catabolic state, severe acidemic uremia may develop. Renal failure usually persists for several weeks, and 30-50% of patients require dialysis.

Angiotensin-converting enzyme (ACE) inhibitors used in the treatment of hypertension appear to have a beneficial effect on renal outcomes of postinfectious Stx– E coli HUS.[77]

Other medical therapies

Trials of gamma globulin are under way, with promising preliminary results. Findings suggest the possibility of some benefit in children.

Azathioprine and vincristine are potent drugs with potential benefit in the management of HUS. Their use falls beyond the scope of this review. Oncologists or others familiar with the use of these drugs should be consulted to review the emerging data about safety and efficacy in HUS and to discuss the risks and principles of management before these agents are administered.

About 25% of patients with HUS who develop neurologic complications (eg, seizures, stroke, coma) may require intensive care.

A small study in Germany used immunoadsorption to rapidly ameliorate severe neurological complications in patients with E Coli 0104:H4-induced HUS.[78] Of the 12 patients enrolled, 10 had total neurological and renal function recovery.

Anticonvulsant therapy may be required to control seizures.

HUS occurring in association with tacrolimus occasionally responds to lowering the dose.

Next

Consultations

See the list below:

  • Pediatric or adult renal specialists should be consulted to manage renal failure.
  • Pediatric or adult rheumatologists should be consulted in cases of HUS associated with neoplasia.
  • Pediatric or adult hematologists may be consulted for the diagnosis and management of hematologic aspects of HUS.
  • Pediatric infectious disease specialists may be consulted for the diagnosis and management of associated infectious illnesses.
  • Pediatric gastroenterologists may be consulted for the management of associated gastroenterologic disease.
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Next

Diet

Special dietary consultation may be necessary to manage renal or gastroenterologic manifestations of HUS. In patients with renal failure, early reduction in protein intake appears to improve long-term renal outcomes.

Previous
Next

Activity

See the list below:

  • Individuals who are shedding infectious agents that elaborate Stx or who may spread other contagions should be restricted, as appropriate for the particular infectious agent.
  • No other specific limitations on activities are needed, except as indicated by the severity of disease and the patient's need for support. Therefore, activities should be advanced as tolerated.
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Contributor Information and Disclosures
Author

Robert Stanley Rust, Jr, MD, MA Thomas E Worrell Jr Professor of Epileptology and Neurology, Co-Director of FE Dreifuss Child Neurology and Epilepsy Clinics, Director, Child Neurology, University of Virginia School of Medicine; Chair-Elect, Child Neurology Section, American Academy of Neurology

Robert Stanley Rust, Jr, MD, MA is a member of the following medical societies: Child Neurology Society, Society for Pediatric Research, American Headache Society, International Child Neurology Association, American Academy of Neurology, American Epilepsy Society, American Neurological Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Nestor Galvez-Jimenez, MD, MSc, MHA The Pauline M Braathen Endowed Chair in Neurology, Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, International Parkinson and Movement Disorder Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

David A Griesemer, MD Professor, Departments of Neuroscience and Pediatrics, Medical University of South Carolina

David A Griesemer, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, Society for Neuroscience, American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Nothing to disclose.

References
  1. Gasser C, Gautier E, Steck A. Haemolotisch-uraemisch syndrome: bilaterale nierindennekrosen bei akuten erworbenen haemolytichen anaemien. Schwiz Med Wochenschr. 1955. 85:174-92.

  2. Lieberman E. Hemolytic-uremic syndrome. J Pediatr. 1972 Jan. 80(1):1-16. [Medline].

  3. Gianantonio CA, Vitacco M, Mendilaharzu F, et al. The hemolytic-uremic syndrome. Nephron. 1973. 11(2):174-92. [Medline].

  4. Vitacco M, Sanchez Avalos J, Gianantonio CA. Heparin therapy in the hemolytic-uremic syndrome. J Pediatr. 1973 Aug. 83(2):271-5. [Medline].

  5. de Chadarevian JP, Kaplan BS. The hemolytic uremic syndrome of childhood. Perspect Pediatr Pathol. 1978. 4:465-502. [Medline].

  6. Silverstein A. Thrombotic thrombocytopenic purpura. The initial neurologic manifestations. Arch Neurol. 1968 Apr. 18(4):358-62. [Medline].

  7. Remuzzi G. HUS and TTP: variable expression of a single entity. Kidney Int. 1987 Aug. 32(2):292-308. [Medline].

  8. Ruggenenti P, Remuzzi G. Thrombotic microangiopathies. Crit Rev Oncol Hematol. 1991 Dec. 11(4):243-65. [Medline].

  9. Wardle EN. Protection against recurrence of acute renal failure. Nephron. 1988. 50(1):81. [Medline].

  10. Drummond KN. Hemolytic uremic syndrome--then and now. N Engl J Med. 1985 Jan 10. 312(2):116-8. [Medline].

  11. Karlsberg RP, Lacher JW, Bartecchi CE. Adult hemolytic-uremic syndrome. Familial variant. Arch Intern Med. 1977 Sep. 137(9):1155-7. [Medline].

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

  13. Martin DL, MacDonald KL, White KE, et al. The epidemiology and clinical aspects of the hemolytic uremic syndrome in Minnesota. N Engl J Med. 1990 Oct 25. 323(17):1161-7. [Medline].

  14. Gianviti A, Tozzi AE, De Petris L, et al. Risk factors for poor renal prognosis in children with hemolytic uremic syndrome. Pediatr Nephrol. 2003 Dec. 18(12):1229-35. [Medline].

  15. Miliwebsky ES, Balbi L, Gomez D, Wainsztein R, Cueto Rua M, Roldan C, et al. Síndrome uremico hemolitico en ninos de Argentina: asociacion con la infección por Escherichia coli productor de toxina Shiga. Bioq Patol Clin. 1999. 63:113-21.

  16. Rivas M, Sosa-Estani S, Rangel J, Caletti MG, Valles P, Roldan CD, et al. Risk factors for sporadic Shiga toxin-producing Escherichia coli infections in children, Argentina. Emerg Infect Dis. 2008 May. 14(5):763-71. [Medline].

  17. Riley LW, Remis RS, Helgerson SD, et al. Hemorrhagic colitis associated with a rare Escherichia coli serotype. N Engl J Med. 1983 Mar 24. 308(12):681-5. [Medline].

  18. Manning SD, Motiwala AS, Springman AC, Qi W, Lacher DW, Ouellette LM, et al. Variation in virulence among clades of Escherichia coli O157:H7 associated with disease outbreaks. Proc Natl Acad Sci U S A. 2008 Mar 25. 105(12):4868-73. [Medline].

  19. Lindqvist R, Antonsson AK, Norling B, et al. The prevalence of verocytotoxin-producing Escherichia coli (VTEC) and E. coli O157:H7 in beef in Sweden determined by PCR assays and an immuno-magnetic separation (IMS) method. Food Microbiology. 1998 Dec. 15(6):591-601.

  20. Cimolai N, Carter JE. Gender and the progression of Escherichia coli O157:H7 enteritis to haemolytic uraemic syndrome. Arch Dis Child. 1991 Jan. 66(1):171-2. [Medline].

  21. Joh K. Predictive indicators for progression to severe complications(hemolytic-uremic syndrome and encephalopathy) and their prevention in enterohemorrhagic Escherichia coli infection [in Japanese]. Nippon Rinsho. 1997 Mar. 55(3):700-5. [Medline].

  22. te Loo DM, Monnens LA, van Der Velden TJ, Vermeer MA, Preyers F, Demacker PN, et al. Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood. 2000 Jun 1. 95(11):3396-402. [Medline].

  23. Te Loo DM, van Hinsbergh VW, van den Heuvel LP, Monnens LA. Detection of verocytotoxin bound to circulating polymorphonuclear leukocytes of patients with hemolytic uremic syndrome. J Am Soc Nephrol. 2001 Apr. 12(4):800-6. [Medline].

  24. Malbrain ML, Lambrecht GL, Brans B. Acute renal failure in non-fulminant hepatitis A. Clin Nephrol. 1994 Mar. 41(3):180-1. [Medline].

  25. Remuzzi G, Bertani T. Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and acute cortical necrosis. Diseases of the Kidney. 1988. 2301.

  26. Tzipori S, Sheoran A, Akiyoshi D, Donohue-Rolfe A, Trachtman H. Antibody therapy in the management of shiga toxin-induced hemolytic uremic syndrome. Clin Microbiol Rev. 2004 Oct. 17(4):926-41, table of contents. [Medline].

  27. Nagayama K. [A novel marker of development of HUS associated with enterohemorrhagic Escherichia coli infection--thrombomodulin levels in the blood]. Nippon Rinsho. 1997 Mar. 55(3):747-50. [Medline].

  28. Chandler WL, Jelacic S, Boster DR, et al. Prothrombotic coagulation abnormalities preceding the hemolytic-uremic syndrome. N Engl J Med. 2002 Jan 3. 346(1):23-32. [Medline].

  29. Tsai HM. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. J Mol Med. 2002 Oct. 80(10):639-47. [Medline].

  30. Hosler GA, Cusumano AM, Hutchins GM. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases. Arch Pathol Lab Med. 2003 Jul. 127(7):834-9. [Medline].

  31. Chow TW, Turner NA, Chintagumpala M, et al. Increased von Willebrand factor binding to platelets in single episode and recurrent types of thrombotic thrombocytopenic purpura. Am J Hematol. 1998 Apr. 57(4):293-302. [Medline].

  32. Tsai HM, Rice L, Sarode R, et al. Antibody inhibitors to von Willebrand factor metalloproteinase and increased binding of von Willebrand factor to platelets in ticlopidine-associated thrombotic thrombocytopenic purpura. Ann Intern Med. 2000 May 16. 132(10):794-9. [Medline].

  33. Tsai HM. Deficiency of ADAMTS-13 in thrombotic and thrombocytopenic purpura. J Thromb Haemost. 2003 Sep. 1(9):2038-40; discussion 2040-5. [Medline].

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

  35. Siegler RL, Pysher TJ, Lou R, Tesh VL, Taylor FB Jr. Response to Shiga toxin-1, with and without lipopolysaccharide, in a primate model of hemolytic uremic syndrome. Am J Nephrol. 2001 Sep-Oct. 21(5):420-5. [Medline].

  36. 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. 2000 Jun 29. 342(26):1930-6. [Medline].

  37. Barnham M, Weightman N. Clostridium septicum infection and hemolytic uremic syndrome. Emerg Infect Dis. 1998 Apr-Jun. 4(2):321-4. [Medline].

  38. Richardson SE, Jagadha V, Smith CR, Becker LE, Petric M, Karmali MA. Annual Meeting of the American Society for Microbiology, Atlanta, 1-6 March 1987 (abstract). Pathological effects on injected H.30 verotoxin (VT) in rabbits.

  39. Tzipori S, Chow CW, Powell HR. Cerebral infection with Escherichia coli O157:H7 in humans and gnotobiotic piglets. J Clin Pathol. 1988 Oct. 41(10):1099-103. [Medline].

  40. Palomeque Rico A, Pastor Durán X, Molinero Egea C, Roca González A. [Hemolytic uremic syndrome. Evaluation of clinical and prognostic factors]. An Esp Pediatr. 1993 Nov. 39(5):391-4. [Medline].

  41. Upadhyaya K, Barwick K, Fishaut M, Kashgarian M, Siegel NJ. The importance of nonrenal involvement in hemolytic-uremic syndrome. Pediatrics. 1980 Jan. 65(1):115-20. [Medline].

  42. Kovacs MJ, Roddy J, Gregoire S, et al. Thrombotic thrombocytopenic purpura following hemorrhagic colitis due to Escherichia coli O157:H7. Am J Med. 1990 Feb. 88(2):177-9. [Medline].

  43. Warwicker P, Goodship JA, Goodship TH. Factor H--US?. Nephrol Dial Transplant. 1998 Aug. 13(8):1921-3. [Medline].

  44. Noris M, Ruggenenti P, Perna A, et al. Hypocomplementemia discloses genetic predisposition to hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: role of factor H abnormalities. Italian Registry of Familial and Recurrent Hemolytic Uremic Syndrome/Thrombotic Thrombocytopenic Pur. J Am Soc Nephrol. 1999 Feb. 10(2):281-93. [Medline].

  45. Noris M, Brioschi S, Caprioli J, Todeschini M, Bresin E, Porrati F, et al. Familial haemolytic uraemic syndrome and an MCP mutation. Lancet. 2003 Nov 8. 362(9395):1542-7. [Medline].

  46. Cooper M, McGraw ME, Unsworth DJ, Mathieson P. Familial mesangio-capillary glomerulonephritis with initial presentation as haemolytic uraemic syndrome. Nephrol Dial Transplant. 2004 Jan. 19(1):230-3. [Medline].

  47. Pérez-Caballero D, González-Rubio C, Gallardo ME, Vera M, López-Trascasa M, Rodríguez de Córdoba S, et al. Clustering of missense mutations in the C-terminal region of factor H in atypical hemolytic uremic syndrome. Am J Hum Genet. 2001 Feb. 68(2):478-84. [Medline].

  48. Richards A, Goodship JA, Goodship TH. The genetics and pathogenesis of haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Curr Opin Nephrol Hypertens. 2002 Jul. 11(4):431-5. [Medline].

  49. Galbusera M, Noris M, Rossi C, et al. Increased fragmentation of von Willebrand factor, due to abnormal cleavage of the subunit, parallels disease activity in recurrent hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and discloses predisposition in families. The Italian R. Blood. 1999 Jul 15. 94(2):610-20. [Medline].

  50. Rodríguez de Cordoba S, Esparza-Gordillo J, Goicoechea de Jorge E, Lopez-Trascasa M, Sanchez-Corral P. The human complement factor H: functional roles, genetic variations and disease associations. Mol Immunol. 2004 Jun. 41(4):355-67. [Medline].

  51. Fortin MC, Schürch W, Cardinal H, Hébert MJ. Complement factor H deficiency in acute allograft glomerulopathy and post-transplant hemolytic uremic syndrome. Am J Transplant. 2004 Feb. 4(2):270-3. [Medline].

  52. Fremeaux-Bacchi V, Dragon-Durey MA, Blouin J, Vigneau C, Kuypers D, Boudailliez B, et al. Complement factor I: a susceptibility gene for atypical haemolytic uraemic syndrome. J Med Genet. 2004 Jun. 41(6):e84. [Medline].

  53. Elliott MK, Jarmi T, Ruiz P, Xu Y, Holers VM, Gilkeson GS. Effects of complement factor D deficiency on the renal disease of MRL/lpr mice. Kidney Int. 2004 Jan. 65(1):129-38. [Medline].

  54. Rougier N, Kazatchkine MD, Rougier JP, et al. Human complement factor H deficiency associated with hemolytic uremic syndrome. J Am Soc Nephrol. 1998 Dec. 9(12):2318-26. [Medline].

  55. Goldstein MH, Churg J, Strauss L, Gribetz D. Hemolytic-uremic syndrome. Nephron. 1979. 23(6):263-72. [Medline].

  56. Lin CC, King KL, Chao YW, Yang AH, Chang CF, Yang WC. Tacrolimus-associated hemolytic uremic syndrome: a case analysis. J Nephrol. 2003 Jul-Aug. 16(4):580-5. [Medline].

  57. Kinney JS, Gross TP, Porter CC, Rogers MF, Schonberger LB, Hurwitz ES. Hemolytic-uremic syndrome: a population-based study in Washington, DC and Baltimore, Maryland. Am J Public Health. 1988 Jan. 78(1):64-5. [Medline].

  58. Cummings KC, Mohle-Boetani JC, Werner SB, Vugia DJ. Population-based trends in pediatric hemolytic uremic syndrome in California, 1994-1999: substantial underreporting and public health implications. Am J Epidemiol. 2002 May 15. 155(10):941-8. [Medline].

  59. Tarr PI, Neill MA, Allen J, et al. The increasing incidence of the hemolytic-uremic syndrome in King County, Washington: lack of evidence for ascertainment bias. Am J Epidemiol. 1989 Mar. 129(3):582-6. [Medline].

  60. Olotu AI, Mithwani S, Newton CR. Haemolytic uraemic syndrome in children admitted to a rural district hospital in Kenya. Trop Doct. 2008 Jul. 38(3):165-7. [Medline].

  61. Ardissino G, Tel F, Testa S, Marzano AV, Lazzari R, Salardi S, et al. Skin Involvement in Atypical Hemolytic Uremic Syndrome. Am J Kidney Dis. 2013 Nov 26. [Medline].

  62. Fong JS, de Chadarevian JP, Kaplan BS. Hemolytic-uremic syndrome. Current concepts and management. Pediatr Clin North Am. 1982 Aug. 29(4):835-56. [Medline].

  63. Wang R, Zhang Y, Li S, Chen H, Zeng C, Chen H, et al. Hemolytic uremic syndrome complicated with IgA nephropathy: a case report and literature review. Clin Nephrol. 2013 Dec 2. [Medline].

  64. Steinborn M, Leiz S, Rüdisser K, Griebel M, Harder T, Hahn H. CT and MRI in haemolytic uraemic syndrome with central nervous system involvement: distribution of lesions and prognostic value of imaging findings. Pediatr Radiol. 2004 Oct. 34(10):805-10. [Medline].

  65. Remuzzi G, Ruggenenti P. The hemolytic uremic syndrome. Kidney Int. 1995 Jul. 48(1):2-19. [Medline].

  66. Ruggenenti P, Remuzzi G. Treatment of adult hemolytic-uremic syndrome. Adv Nephrol Necker Hosp. 2000. 30:83-94. [Medline].

  67. Arenson EB, August CS. Preliminary report: treatment of the hemolytic-uremic syndrome with aspirin and dipyridamole. J Pediatr. 1975 Jun. 86(6):957-61. [Medline].

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

  69. Soliris (eculizumab) [package insert]. Cheshire, CT: Alexion Pharmaceuticals. Sept 2011. Available at [Full Text].

  70. Verweyen HM, Karch H, Allerberger F, Zimmerhackl LB. Enterohemorrhagic Escherichia coli (EHEC) in pediatric hemolytic-uremic syndrome: a prospective study in Germany and Austria. Infection. 1999 Nov-Dec. 27(6):341-7. [Medline].

  71. Loirat C, Babu S, Furman R, Sheerin N, Cohen D, Gaber O, et al. Eculizumab Efficacy and Safety in Patients With Atypical Hemolytic Uremic Syndrome (aHUS) Resistant to Plasma Exchange/Infusion [poster]. Presented at the 16th Congress of European Hematology Association (EHA). 2011. London, UK.

  72. Loirat C, Muus P, Legendre C, Douglas K, Hourmant M, Delmas Y, et al. A Phase II Study of Eculizumab in Patients With Atypical Hemolytic Uremic Syndrome Receiving Chronic Plasma Exchange/Infusion [poster]. Presented at the 16th Congress of European Hematology Association (EHA). 2011. London, UK.

  73. Hu H, Nagra A, Haq MR, Gilbert RD. Eculizumab in atypical haemolytic uraemic syndrome with severe cardiac and neurological involvement. Pediatr Nephrol. 2013 Dec 8. [Medline].

  74. Vitacco M, Sanchez Avalos J, Gianantonio CA. Heparin therapy in the hemolytic-uremic syndrome. J Pediatr. 1973 Aug. 83(2):271-5. [Medline].

  75. Van Damme-Lombaerts R, Proesmans W, Van Damme B, Eeckels R, Binda ki Muaka P, Mercieca V. Heparin plus dipyridamole in childhood hemolytic-uremic syndrome: a prospective, randomized study. J Pediatr. 1988 Nov. 113(5):913-8. [Medline].

  76. Armstrong GD, Rowe PC, Goodyer P, Orrbine E, Klassen TP, Wells G. A phase I study of chemically synthesized verotoxin (Shiga-like toxin) Pk-trisaccharide receptors attached to chromosorb for preventing hemolytic-uremic syndrome. J Infect Dis. 1995 Apr. 171(4):1042-5. [Medline].

  77. Van Dyck M, Proesmans W. Renoprotection by ACE inhibitors after severe hemolytic uremic syndrome. Pediatr Nephrol. 2004 Jun. 19(6):688-90. [Medline].

  78. Greinacher A, Friesecke S, Abel P, Dressel A, Stracke S, Fiene M, et al. Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial. Lancet. 2011 Sep 24. 378(9797):1166-73. [Medline].

  79. Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA. 2003 Sep 10. 290(10):1360-70. [Medline].

  80. Siegler RL. Postdiarrheal Shiga toxin-mediated hemolytic uremic syndrome. JAMA. 2003 Sep 10. 290(10):1379-81. [Medline].

  81. Placeholder.

  82. Baker KR, Moake JL. Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Curr Opin Pediatr. 2000 Feb. 12(1):23-8. [Medline].

  83. Banatvala N, Griffin PM, Greene KD, et al. The United States National Prospective Hemolytic Uremic Syndrome Study: microbiologic, serologic, clinical, and epidemiologic findings. J Infect Dis. 2001 Apr 1. 183(7):1063-70. [Medline].

  84. Bassani CE, Ferraris J, Gianantonio CA, et al. Renal transplantation in patients with classical haemolytic-uraemic syndrome. Pediatr Nephrol. 1991 Sep. 5(5):607-11. [Medline].

  85. Beattie TJ, Murphy AV, Willoughby ML, Belch JJ. Prostacyclin infusion in haemolytic-uraemic syndrome of children. Br Med J (Clin Res Ed). 1981 Aug 15. 283(6289):470. [Medline].

  86. Beattie TJ, Murphy AV, Willoughby ML, et al. Plasmapheresis in the haemolytic-uraemic syndrome in children. Br Med J (Clin Res Ed). 1981 May 23. 282(6277):1667-8. [Medline].

  87. Blaker F, Altrogge H, Hellwege HH, et al. Treatment of severe haemolytic-uraemic syndrome by dialysis [in German]. Dtsch Med Wochenschr. 1978 Aug 4. 103(31):1229-32. [Medline].

  88. Bohle A, Helmchen U, Grund KE, et al. Malignant nephrosclerosis in patients with hemolytic uremic syndrome (primary malignant nephrosclerosis). Curr Top Pathol. 1977. 65:81-113. [Medline].

  89. Bukowski RM, Hewlett JS, Harris JW, et al. Exchange transfusions in the treatment of thrombotic thrombocytopenic purpura. Semin Hematol. 1976 Jul. 13(3):219-32. [Medline].

  90. Byrnes JJ, Moake JL. Thrombotic thrombocytopenic purpura and the haemolytic-uraemic syndrome: evolving concepts of pathogenesis and therapy. Clin Haematol. 1986 May. 15(2):413-42. [Medline].

  91. Caprioli A, Luzzi I, Rosmini F, et al. Hemolytic-uremic syndrome and Vero cytotoxin-producing Escherichia coli infection in Italy. The HUS Italian Study Group. J Infect Dis. 1992 Jul. 166(1):154-8. [Medline].

  92. Caprioli A, Tozzi AE, Rizzoni G, Karch H. Non-O157 Shiga toxin-producing Escherichia coli infections in Europe. Emerg Infect Dis. 1997 Oct-Dec. 3(4):578-9. [Medline].

  93. Cimolai N, Basalyga S, Mah DG, et al. A continuing assessment of risk factors for the development of Escherichia coli O157:H7-associated hemolytic uremic syndrome. Clin Nephrol. 1994 Aug. 42(2):85-9. [Medline].

  94. Cimolai N, Carter JE. Antimotility agents for paediatric use. Lancet. 1990 Oct 6. 336(8719):874. [Medline].

  95. Cimolai N, Carter JE. Bacterial genotype and neurological complications of Escherichia coli O157:H7-associated haemolytic uraemic syndrome. Acta Paediatr. 1998 May. 87(5):593-4. [Medline].

  96. Cimolai N, Carter JE, Morrison BJ, Anderson JD. Risk factors for the progression of Escherichia coli O157:H7 enteritis to hemolytic-uremic syndrome. J Pediatr. 1990 Apr. 116(4):589-92. [Medline].

  97. Cimolai N, Morrison BJ, Carter JE. Risk factors for the central nervous system manifestations of gastroenteritis-associated hemolytic-uremic syndrome. Pediatrics. 1992 Oct. 90(4):616-21. [Medline].

  98. Coad NA, Marshall T, Rowe B, Taylor CM. Changes in the postenteropathic form of the hemolytic uremic syndrome in children. Clin Nephrol. 1991 Jan. 35(1):10-6. [Medline].

  99. Decludt B, Bouvet P, Mariani-Kurkdjian P, et al. Haemolytic uraemic syndrome and Shiga toxin-producing Escherichia coli infection in children in France. The Societe de Nephrologie Pediatrique. Epidemiol Infect. 2000 Apr. 124(2):215-20. [Medline].

  100. Drews RE, Weinberger SE. Thrombocytopenic disorders in critically ill patients. Am J Respir Crit Care Med. 2000 Aug. 162(2 Pt 1):347-51. [Medline].

  101. Ekberg M, Holmberg L, Denneberg T. Hemolytic uremic syndrome. Results of treatment with hemodialysis. Acta Paediatr Scand. 1977 Nov. 66(6):693-8. [Medline].

  102. Elliott MA, Nichols WL. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Mayo Clin Proc. 2001 Nov. 76(11):1154-62. [Medline].

  103. Fakhouri F, Vincent F, Legendre C. Pathological and therapeutic distinctions in HUS/TTP. Lancet. 2000 Feb 5. 355(9202):497; author reply 497-8. [Medline].

  104. Fitzpatrick MM, Walters MD, Trompeter RS, et al. Atypical (non-diarrhea-associated) hemolytic-uremic syndrome in childhood. J Pediatr. 1993 Apr. 122(4):532-7. [Medline].

  105. Fong JS, Kaplan BS. Impairment of platelet aggregation in hemolytic uremic syndrome: evidence for platelet "exhaustion". Blood. 1982 Sep. 60(3):564-70. [Medline].

  106. 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. 2005 Nov. 42(11):852-6. [Medline].

  107. Furlan M, Lammle B. Haemolytic-uraemic syndrome and thrombotic thrombocytopenic purpura--new insights into underlying biochemical mechanisms. Nephrol Dial Transplant. 2000 Aug. 15(8):1112-4. [Medline].

  108. Gallo EG, Gianantonio CA. Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome. Pediatr Nephrol. 1995 Feb. 9(1):117-9. [Medline].

  109. Gianviti A, Perna A, Caringella A, et al. Plasma exchange in children with hemolytic-uremic syndrome at risk of poor outcome. Am J Kidney Dis. 1993 Aug. 22(2):264-6. [Medline].

  110. Griffin PM, Tauxe RV. The epidemiology of infections caused by Escherichia coli O157:H7, other enterohemorrhagic E. coli, and the associated hemolytic uremic syndrome. Epidemiol Rev. 1991. 13:60-98. [Medline].

  111. Hammond D, Lieberman E. The hemolytic uremic syndrome. Renal cortical thrombotic microangiopathy. Arch Intern Med. 1970 Nov. 126(5):816-22. [Medline].

  112. Heusser. hemolytic uremic syndrome. 1966.

  113. Jeong YK, Kim IO, Kim WS, et al. Hemolytic uremic syndrome: MR findings of CNS complications. Pediatr Radiol. 1994. 24(8):585-6. [Medline].

  114. Kakishita E. Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Int J Hematol. 2000 Jun. 71(4):320-7. [Medline].

  115. Kaplan BS, Thomson PD. Hyperuricemia in the hemolytic-uremic syndrome. Am J Dis Child. 1976 Aug. 130(8):854-6. [Medline].

  116. Kaplan BS, Thomson PD, de Chadarevian JP. The hemolytic uremic syndrome. Pediatr Clin North Am. 1976 Nov. 23(4):761-77. [Medline].

  117. Karmali MA, Petric M, Lim C, et al. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis. 1985 May. 151(5):775-82. [Medline].

  118. Lieberman E, Heuser E, Donnell GN, et al. Hemolytic-uremic syndrome. Clinical and pathological considerations. N Engl J Med. 1966 Aug 4. 275(5):227-36. [Medline].

  119. Loirat C, Beaufils F, Sonsino E, et al. Treatment of childhood hemolytic-uremic syndrome with urokinase. Cooperative controlled trial [in French]. Arch Fr Pediatr. 1984 Jan. 41(1):15-9. [Medline].

  120. Loirat C, Niaudet P. The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children. Pediatr Nephrol. 2003 Nov. 18(11):1095-101. [Medline].

  121. Lopez EL, Devoto S, Fayad A, et al. Association between severity of gastrointestinal prodrome and long-term prognosis in classic hemolytic-uremic syndrome. J Pediatr. 1992 Feb. 120(2 Pt 1):210-5. [Medline].

  122. Marques MB, Mayfield CA, Blackall DP. Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma. Am J Clin Pathol. 2004 Jun. 121 Suppl:S89-96. [Medline].

  123. Ohali M, Shalev H, Schlesinger M, et al. Hypocomplementemic autosomal recessive hemolytic uremic syndrome with decreased factor H. Pediatr Nephrol. 1998 Oct. 12(8):619-24. [Medline].

  124. Olinsky A, Thomson P, Kaplan B, Abrahams C. Analysis of 10 cases of the haemolytic-uraemic syndrome seen at the Transvaal Memorial Hospital for Children in the 18-month period January 1970 to June 1971. S Afr Med J. 1972 Jun 17. 46(25):848. [Medline].

  125. Ostroff SM, Tarr PI, Neill MA, et al. Toxin genotypes and plasmid profiles as determinants of systemic sequelae in Escherichia coli O157:H7 infections. J Infect Dis. 1989 Dec. 160(6):994-8. [Medline].

  126. Pichette V, Querin S, Schurch W, et al. Familial hemolytic-uremic syndrome and homozygous factor H deficiency. Am J Kidney Dis. 1994 Dec. 24(6):936-41. [Medline].

  127. Ray PE, Liu XH. Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. Pediatr Nephrol. 2001 Oct. 16(10):823-39. [Medline].

  128. Remis RS, MacDonald KL, Riley LW, et al. Sporadic cases of hemorrhagic colitis associated with Escherichia coli O157:H7. Ann Intern Med. 1984 Nov. 101(5):624-6. [Medline].

  129. Remuzzi G, Ruggenenti P. The hemolytic uremic syndrome. Kidney Int Suppl. 1998 May. 66:S54-7. [Medline].

  130. Remuzzi G, Zoja C, de Gaetano G, Rossi EC. Prostacyclin and hemolytic uremic syndrome: from the laboratory to an international registry. Int J Artif Organs. 1987 Nov. 10(6):337-40. [Medline].

  131. Renaud C, Niaudet P, Gagnadoux MF, et al. Haemolytic uraemic syndrome: prognostic factors in children over 3 years of age. Pediatr Nephrol. 1995 Feb. 9(1):24-9. [Medline].

  132. Rizzoni G, Claris-Appiani A, Edefonti A, et al. Plasma infusion for hemolytic-uremic syndrome in children: results of a multicenter controlled trial. J Pediatr. 1988 Feb. 112(2):284-90. [Medline].

  133. Ruggenenti P, Remuzzi G. The pathophysiology and management of thrombotic thrombocytopenic purpura. Eur J Haematol. 1996 Apr. 56(4):191-207. [Medline].

  134. Sheth KJ, Swick HM, Haworth N. Neurological involvement in hemolytic-uremic syndrome. Ann Neurol. 1986 Jan. 19(1):90-3. [Medline].

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

  136. Siegler RL, Milligan MK, Burningham TH, et al. Long-term outcome and prognostic indicators in the hemolytic-uremic syndrome. J Pediatr. 1991 Feb. 118(2):195-200. [Medline].

  137. Siegler RL, Pavia AT, Christofferson RD, Milligan MK. A 20-year population-based study of postdiarrheal hemolytic uremic syndrome in Utah. Pediatrics. 1994 Jul. 94(1):35-40. [Medline].

  138. Siegler RL, Pavia AT, Hansen FL, et al. Atypical hemolytic-uremic syndrome: a comparison with postdiarrheal disease. J Pediatr. 1996 Apr. 128(4):505-11. [Medline].

  139. Spizzirri FD, Rahman RC, Bibiloni N, et al. Childhood hemolytic uremic syndrome in Argentina: long-term follow-up and prognostic features. Pediatr Nephrol. 1997 Apr. 11(2):156-60. [Medline].

  140. Tarr PI, Tsai HM, Chandler WL. Thrombotic microangiopathies. N Engl J Med. 2002 Dec 26. 347(26):2171-3; author reply 2171-3. [Medline].

  141. Tozzi AE, Caprioli A, Minelli F, et al. Shiga toxin-producing Escherichia coli infections associated with hemolytic uremic syndrome, Italy, 1988-2000. Emerg Infect Dis. 2003 Jan. 9(1):106-8. [Medline].

  142. Trompeter RS, Schwartz R, Chantler C, et al. Haemolytic-uraemic syndrome: an analysis of prognostic features. Arch Dis Child. 1983 Feb. 58(2):101-5. [Medline].

  143. Walters MD, Matthei IU, Kay R, et al. The polymorphonuclear leucocyte count in childhood haemolytic uraemic syndrome. Pediatr Nephrol. 1989 Apr. 3(2):130-4. [Medline].

  144. Wells JG, Davis BR, Wachsmuth IK, et al. Laboratory investigation of hemorrhagic colitis outbreaks associated with a rare Escherichia coli serotype. J Clin Microbiol. 1983 Sep. 18(3):512-20. [Medline].

 
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Peripheral smear in hemolytic uremic syndrome, with findings of microangiopathic hemolytic anemia. Note schistocytes/helmet cells, as well as decrease in platelets. Image courtesy of Emma Z Du, MD.
 
 
 
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