Diagnostic Considerations

Atypical HUS (aHUS) is a genetic-related subtype. It is previous known as diarrhea-negative subtype. As the matter of fact, diarrhea is not uncommon in aHUS anymore. Therefore, the term diarrhea-negative HUS is no longer accepted. This genetic defect causes predispose to develop aHUS via mostly alternative pathway of immune complement system. The other noncomplement-associated genetic defect in aHUS includes mutation of diacylglycerol kinase epsilon (DGKE) and deficiencies in Cobalamin C. It is an extremely rare disease with incidence of just between 0.5 and 2 per million. Although aHUS is commonly found in very young children especially age under 2 years old, it may be presented in older children and adult.^{[62, 64]}

Genetic defect in aHUS

Complement-associated

Mutations in Factor H (FH)
Mutations in Factor I (FI)
Mutations in Factor B (FB)
Mutations in Membrane Cofactor Protein (MCP/CD46)
C3 Mutations
Antibodies Against Complement Factor H
Thrombomodulin Mutations
Noncomplement-associated
- diacylglycerol kinase epsilon (DGKE) Mutations
- Cobalamin C

Potential characteristics of aHUS include:

lack of infection-associated cause
non-synchronous HUS in a family member
recurrent disease
a prolonged relapsing/remitting course
indolent course of illness
onset prior to age 6 months

Differential Diagnoses

Workup

Gasser C, Gautier E, Steck A. Haemolotisch-uraemisch syndrome: bilaterale nierindennekrosen bei akuten erworbenen haemolytichen anaemien. Schwiz Med Wochenschr. 1955. 85:174-92.
Lieberman E. Hemolytic-uremic syndrome. J Pediatr. 1972 Jan. 80(1):1-16. [QxMD MEDLINE Link].
Gianantonio CA, Vitacco M, Mendilaharzu F, et al. The hemolytic-uremic syndrome. Nephron. 1973. 11(2):174-92. [QxMD MEDLINE Link].
Vitacco M, Sanchez Avalos J, Gianantonio CA. Heparin therapy in the hemolytic-uremic syndrome. J Pediatr. 1973 Aug. 83(2):271-5. [QxMD MEDLINE Link].
de Chadarevian JP, Kaplan BS. The hemolytic uremic syndrome of childhood. Perspect Pediatr Pathol. 1978. 4:465-502. [QxMD MEDLINE Link].
Silverstein A. Thrombotic thrombocytopenic purpura. The initial neurologic manifestations. Arch Neurol. 1968 Apr. 18(4):358-62. [QxMD MEDLINE Link].
Remuzzi G. HUS and TTP: variable expression of a single entity. Kidney Int. 1987 Aug. 32(2):292-308. [QxMD MEDLINE Link].
Ruggenenti P, Remuzzi G. Thrombotic microangiopathies. Crit Rev Oncol Hematol. 1991 Dec. 11(4):243-65. [QxMD MEDLINE Link].
Wardle EN. Protection against recurrence of acute renal failure. Nephron. 1988. 50(1):81. [QxMD MEDLINE Link].
Drummond KN. Hemolytic uremic syndrome--then and now. N Engl J Med. 1985 Jan 10. 312(2):116-8. [QxMD MEDLINE Link].
Karlsberg RP, Lacher JW, Bartecchi CE. Adult hemolytic-uremic syndrome. Familial variant. Arch Intern Med. 1977 Sep. 137(9):1155-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Malbrain ML, Lambrecht GL, Brans B. Acute renal failure in non-fulminant hepatitis A. Clin Nephrol. 1994 Mar. 41(3):180-1. [QxMD MEDLINE Link].
Remuzzi G, Bertani T. Thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and acute cortical necrosis. Diseases of the Kidney. 1988. 2301.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Tsai HM. Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura. J Mol Med. 2002 Oct. 80(10):639-47. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Tsai HM. Deficiency of ADAMTS-13 in thrombotic and thrombocytopenic purpura. J Thromb Haemost. 2003 Sep. 1(9):2038-40; discussion 2040-5. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Barnham M, Weightman N. Clostridium septicum infection and hemolytic uremic syndrome. Emerg Infect Dis. 1998 Apr-Jun. 4(2):321-4. [QxMD MEDLINE Link].
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.
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Warwicker P, Goodship JA, Goodship TH. Factor H--US?. Nephrol Dial Transplant. 1998 Aug. 13(8):1921-3. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Goldstein MH, Churg J, Strauss L, Gribetz D. Hemolytic-uremic syndrome. Nephron. 1979. 23(6):263-72. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Balgradean M, Croitoru A, Leibovitz E. An outbreak of hemolytic uremic syndrome in southern Romania during 2015-2016: Epidemiologic, clinical, laboratory, microbiologic, therapeutic and outcome characteristics. Pediatr Neonatol. 2019 Feb. 60 (1):87-94. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
[Guideline] Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, et al. Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol. 2009 Apr. 24 (4):687-96. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
Reyes, Laura Castellanos Saland, Jeffrey M. Hemolytic Uremic Syndrome, Genetic. Trachtman H., Herlitz L., Lerma E., Hogan J. Glomerulonephritis. Springer, Cham; 667-679. [Full Text].
Fong JS, de Chadarevian JP, Kaplan BS. Hemolytic-uremic syndrome. Current concepts and management. Pediatr Clin North Am. 1982 Aug. 29(4):835-56. [QxMD MEDLINE Link].
Sarode R, Bandarenko N, Brecher ME, Kiss JE, Marques MB, Szczepiorkowski ZM, et al. Thrombotic thrombocytopenic purpura: 2012 American Society for Apheresis (ASFA) consensus conference on classification, diagnosis, management, and future research. J Clin Apher. 2014 Jun. 29 (3):148-67. [QxMD MEDLINE Link]. [Full Text].
Sadler JE. What's new in the diagnosis and pathophysiology of thrombotic thrombocytopenic purpura. Hematology Am Soc Hematol Educ Program. 2015. 2015:631-6. [QxMD MEDLINE Link]. [Full Text].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Remuzzi G, Ruggenenti P. The hemolytic uremic syndrome. Kidney Int. 1995 Jul. 48(1):2-19. [QxMD MEDLINE Link].
Ruggenenti P, Remuzzi G. Treatment of adult hemolytic-uremic syndrome. Adv Nephrol Necker Hosp. 2000. 30:83-94. [QxMD MEDLINE Link].
Arenson EB, August CS. Preliminary report: treatment of the hemolytic-uremic syndrome with aspirin and dipyridamole. J Pediatr. 1975 Jun. 86(6):957-61. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Soliris (eculizumab) [package insert]. Cheshire, CT: Alexion Pharmaceuticals. Sept 2011. Available at [Full Text].
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.
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.
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. [QxMD MEDLINE Link].
Ultomiris (ravulizumab) [package insert]. Boston, MA: Alexion Pharmaceuticals, Inc. October 2019. Available at [Full Text].
Vitacco M, Sanchez Avalos J, Gianantonio CA. Heparin therapy in the hemolytic-uremic syndrome. J Pediatr. 1973 Aug. 83(2):271-5. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Van Dyck M, Proesmans W. Renoprotection by ACE inhibitors after severe hemolytic uremic syndrome. Pediatr Nephrol. 2004 Jun. 19(6):688-90. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Siegler RL. Postdiarrheal Shiga toxin-mediated hemolytic uremic syndrome. JAMA. 2003 Sep 10. 290(10):1379-81. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Placeholder.
Baker KR, Moake JL. Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Curr Opin Pediatr. 2000 Feb. 12(1):23-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Cimolai N, Carter JE. Antimotility agents for paediatric use. Lancet. 1990 Oct 6. 336(8719):874. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Drews RE, Weinberger SE. Thrombocytopenic disorders in critically ill patients. Am J Respir Crit Care Med. 2000 Aug. 162(2 Pt 1):347-51. [QxMD MEDLINE Link].
Ekberg M, Holmberg L, Denneberg T. Hemolytic uremic syndrome. Results of treatment with hemodialysis. Acta Paediatr Scand. 1977 Nov. 66(6):693-8. [QxMD MEDLINE Link].
Elliott MA, Nichols WL. Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Mayo Clin Proc. 2001 Nov. 76(11):1154-62. [QxMD MEDLINE Link].
Fakhouri F, Vincent F, Legendre C. Pathological and therapeutic distinctions in HUS/TTP. Lancet. 2000 Feb 5. 355(9202):497; author reply 497-8. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Fong JS, Kaplan BS. Impairment of platelet aggregation in hemolytic uremic syndrome: evidence for platelet "exhaustion". Blood. 1982 Sep. 60(3):564-70. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Gallo EG, Gianantonio CA. Extrarenal involvement in diarrhoea-associated haemolytic-uraemic syndrome. Pediatr Nephrol. 1995 Feb. 9(1):117-9. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Hammond D, Lieberman E. The hemolytic uremic syndrome. Renal cortical thrombotic microangiopathy. Arch Intern Med. 1970 Nov. 126(5):816-22. [QxMD MEDLINE Link].
Heusser. hemolytic uremic syndrome. 1966.
Jeong YK, Kim IO, Kim WS, et al. Hemolytic uremic syndrome: MR findings of CNS complications. Pediatr Radiol. 1994. 24(8):585-6. [QxMD MEDLINE Link].
Kakishita E. Pathophysiology and treatment of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). Int J Hematol. 2000 Jun. 71(4):320-7. [QxMD MEDLINE Link].
Kaplan BS, Thomson PD. Hyperuricemia in the hemolytic-uremic syndrome. Am J Dis Child. 1976 Aug. 130(8):854-6. [QxMD MEDLINE Link].
Kaplan BS, Thomson PD, de Chadarevian JP. The hemolytic uremic syndrome. Pediatr Clin North Am. 1976 Nov. 23(4):761-77. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Marques MB, Mayfield CA, Blackall DP. Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma. Am J Clin Pathol. 2004 Jun. 121 Suppl:S89-96. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ray PE, Liu XH. Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome. Pediatr Nephrol. 2001 Oct. 16(10):823-39. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Remuzzi G, Ruggenenti P. The hemolytic uremic syndrome. Kidney Int Suppl. 1998 May. 66:S54-7. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Ruggenenti P, Remuzzi G. The pathophysiology and management of thrombotic thrombocytopenic purpura. Eur J Haematol. 1996 Apr. 56(4):191-207. [QxMD MEDLINE Link].
Sheth KJ, Swick HM, Haworth N. Neurological involvement in hemolytic-uremic syndrome. Ann Neurol. 1986 Jan. 19(1):90-3. [QxMD MEDLINE Link].
Siegler R, Oakes R. Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr. 2005 Apr. 17(2):200-4. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
Tarr PI, Tsai HM, Chandler WL. Thrombotic microangiopathies. N Engl J Med. 2002 Dec 26. 347(26):2171-3; author reply 2171-3. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].
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. [QxMD MEDLINE Link].

Media Gallery

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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Author

Sombat Muengtaweepongsa, MD, MSc Professor, Center of Excellence in Stroke, Associate Dean for Research and Innovations, Department of Neurology, Faculty of Medicine, Thammasat University, Thailand

Sombat Muengtaweepongsa, MD, MSc is a member of the following medical societies: American Academy of Neurology, Royal College of Physicians of Thailand

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Boehringer Ingelheim; Astra Zeneca; Novo Nordisk; Daiichi Sankyo; Bayer<br/>Received research grant from: Faculty of Medicine, Thammasat University.

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 (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

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.

Robert Stanley Rust, Jr, MD, MA Former 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: American Academy of Neurology, American Epilepsy Society, American Headache Society, American Neurological Association, Child Neurology Society, International Child Neurology Association, Society for Pediatric Research

Disclosure: Nothing to disclose.