Hemolytic-Uremic Syndrome Workup
- Author: Malvinder S Parmar, MB, MS; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP more...
Laboratory studies for hemolytic-uremic syndrome (HUS) may include the following:
Urinalysis: Benign mild proteinuria is frequently present; red blood cells (RBCs) and RBC casts may be present
Measurement of blood urea nitrogen (BUN), serum creatinine, and serum electrolyte levels
Hematologic determination: Severe anemia may be present. Perform peripheral smear for schistocytes (count >1% or two or more schistocytes in a 100× magnification field strongly suggests microangiopathic hemolysis).  The degree of thrombocytopenia is not correlated with the severity or the length of illness HUS. The platelet count usually returns to normal within 2 weeks. Determine activated partial thromboplastin time (aPTT), fibrinogen degradation product (FDP), and D-dimer values.
Hemolytic workup: Results may show anemia. Bilirubin levels may be elevated. Lactate dehydrogenase (LDH) levels may be elevated. Haptoglobin levels may be decreased.
Stool culture: Obtain a sample for stool culture. Evaluate especially for E coli 0157:H7 and Shigella bacteria.
ADAMTS-13 activity: ADAMTS-13 activity is often severely deficient (< 10% of normal) in patients with classic thrombotic thrombocytopenic purpura (TTP), but can be seen in patients with severe sepsis (especially in association with disseminated intravascular coagulation or multiorgan failure) and in patients with severe liver disease.
Perform renal ultrasonography in patients with renal failure to rule out obstruction.
Biopsy findings pathologically establish the diagnosis of hemolytic-uremic syndrome (HUS). However, kidney biopsy is not required in children. In adults, kidney biopsy is rarely required.
The characteristic pathologic findings of hemolytic-uremic syndrome (HUS) are occlusive lesions of the arterioles and small arteries and consequent tissue microinfarctions. In HUS, the lesions are usually limited to the kidneys, whereas the lesions are more widespread in thrombotic thrombocytopenic purpura (TTP). Renal lesions are primarily focal and involve both the glomerular capillaries and the afferent arterioles. The venous side of the circulation is usually spared.
A fully developed vascular lesion consists of amorphous-appearing, hyalinelike, thrombi-containing platelet aggregates and a small amount of fibrin that partially or fully occludes the involved small vessels (see images below). Despite extensive arterial changes, no perivascular cellular infiltration or evidence of associated vasculitis is present. Subendothelial deposits with overlying endothelial proliferation may be present.
As a rule, changes in renal function and the course of renal failure are well correlated with the pathologic findings in the kidney. Obliterative arteriolar lesions are correlated with hypertension and progressive loss of renal function. Glomerular thrombotic microangiopathic lesions and cortical necrosis are the most frequent histologic findings in Stx-HUS, whereas arterial thrombotic microangiopathic lesions are the most frequent features in non – Stx-HUS.
Keir LS. Shiga toxin associated hemolytic uremic syndrome. Hematol Oncol Clin North Am. 2015 Jun. 29 (3):525-39. [Medline].
Conway EM. HUS and the case for complement. Blood. 2015 Oct 29. 126 (18):2085-90. [Medline].
Siegler RL. Management of hemolytic-uremic syndrome. J Pediatr. 1988 Jun. 112(6):1014-20. [Medline].
Siegler R, Oakes R. Hemolytic uremic syndrome; pathogenesis, treatment, and outcome. Curr Opin Pediatr. 2005 Apr. 17(2):200-4. [Medline].
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. 1998 Nov 26. 339(22):1578-84. [Medline]. [Full Text].
George JN. ADAMTS13, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. Curr Hematol Rep. 2005 May. 4(3):167-9. [Medline].
Haspel RL, Jarolím P. The "cutting" edge: von Willebrand factor-cleaving protease activity in thrombotic microangiopathies. Transfus Apher Sci. 2005 Apr. 32(2):177-84. [Medline].
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].
Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005 Mar 19-25. 365(9464):1073-86. [Medline].
Frank C, Werber D, Cramer JP, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011 Nov 10. 365(19):1771-80. [Medline].
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. 2001 Feb. 12(2):297-307. [Medline]. [Full Text].
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. 2005 Nov. 42(11):852-6. [Medline]. [Full Text].
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. 2008 Mar. 51(3):487-90. [Medline].
Lapeyraque AL, Wagner E, Phan V, et al. Efficacy of plasma therapy in atypical hemolytic uremic syndrome with complement factor H mutations. Pediatr Nephrol. 2008 Aug. 23(8):1363-6. [Medline].
Kojouri K, Vesely SK, George JN. Quinine-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: frequency, clinical features, and long-term outcomes. Ann Intern Med. 2001 Dec 18. 135(12):1047-51. [Medline].
Schuppner R, Maehlmann J, Dirks M, Worthmann H, Tryc AB, Sandorski K, et al. Neurological Sequelae in Adults After E coli O104: H4 Infection-Induced Hemolytic-Uremic Syndrome. Medicine (Baltimore). 2016 Feb. 95 (6):e2337. [Medline].
Santos AH Jr, Casey MJ, Wen X, Zendejas I, Faldu C, Rehman S, et al. Outcome of kidney transplants for adults with hemolytic uremic syndrome in the U.S.: a ten-year database analysis. Ann Transplant. 2014 Jul 21. 19:353-61. [Medline].
Burns ER, Lou Y, Pathak A. Morphologic diagnosis of thrombotic thrombocytopenic purpura. Am J Hematol. 2004 Jan. 75(1):18-21. [Medline].
McGannon CM, Fuller CA, Weiss AA. Different classes of antibiotics differentially influence Shiga toxin production. Antimicrob Agents Chemother. 2010 Sept. 54(9):3790-3798.
Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev. 2009 Jan 21. CD003595. [Medline].
FDA approves Soliris for rare pediatric blood disorder. U.S. Food and Drug Administration. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm272990.htm. Accessed: December 14, 2014.
Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013 Jun 6. 368(23):2169-81. [Medline]. [Full Text].
Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO, et al. Terminal Complement Inhibitor Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome: A Single-Arm, Open-Label Trial. Am J Kidney Dis. 2016 Mar 16. [Medline].
Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016 Mar. 89 (3):701-11. [Medline]. [Full Text].
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]. [Full Text].
Davis AK, Makar RS, Stowell CP, Kuter DJ, Dzik WH. ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial localization of ADAMTS13. Transfusion. 2009 Feb. 49(2):206-13. [Medline].
Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009 Oct 22. 361(17):1676-87. [Medline].