Pediatric Hemolytic Uremic Syndrome Workup

Updated: Nov 12, 2018
  • Author: Robert S Gillespie, MD, MPH; Chief Editor: Craig B Langman, MD  more...
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Workup

Laboratory Studies

Hematology

Classic findings in hemolytic-uremic syndrome (HUS) include anemia and thrombocytopenia, with fragmented RBCs (eg, schistocytes, helmet cells, burr cells), as shown in the image below.

Peripheral blood smear in hemolytic-uremic syndrom Peripheral blood smear in hemolytic-uremic syndrome (HUS) showing many schistocytes and RBC fragments due to hemolysis, and relatively few platelets reflective of thrombocytopenia.

Testing for ADAMTS13 activity may help distinguish between atypical hemolytic-uremic syndrome (aHUS) and thrombotic thrombocytopenic purpura (TTP). ADAMTS13 activity less than 10% is consistent with a diagnosis of TTP. Patients with low levels of ADAMTS13 activity should also be tested for the presence of antibody to ADAMTS13. If plasma exchange is planned, specimens should be obtained before starting plasma exchange, as the donor plasma may confound the results. Rapid diagnosis is very helpful. Several laboratories offer 24-hour turnaround service.

WBC differential may reveal a left shift (ie, immature WBCs, including bands, myelocytes, metamyelocytes). Patients with Shiga toxin–producing E coli hemolytic-uremic syndrome (STEC-HUS) may have extremely high WBC counts, in the range of 50,000-60,000/µL.

Coombs test results are negative, except with S pneumoniae –associated hemolytic-uremic syndrome.

Reticulocyte count is elevated.

levels of serum haptoglobin, which binds hemoglobin, are decreased.

Prothrombin time (PT) and activated partial thromboplastin time (aPTT) are normal.

Fibrin degradation products are increased.

Fibrinogen levels are increased or within reference range.

Serum chemistry testing

BUN and creatinine levels are elevated.

Various electrolyte and ion derangements may be present because of vomiting, diarrhea, dehydration, and renal failure; these may include hyponatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidosis. Phosphorus concentration is elevated.

Uric acid level may be increased because of acute renal failure, dehydration, and cell breakdown.

Protein (see Serum Protein Electrophoresis) and albumin levels may be mildly decreased.

Bilirubin and aminotransferase (see Alanine Aminotransferase and Aspartate Aminotransferase) levels are typically elevated.

Lactate dehydrogenase (LDH) level is elevated. Serial measurements of LDH help track the approximate level of hemolytic activity.

Urinalysis

Urinalysis should be performed to assess the following:

  • Protein

  • Heme

  • Bilirubin

  • RBCs (dysmorphic)

  • WBCs

  • Casts - Cellular, granular, pigmented, hyaline

Stool testing

Usually, culture yield is low after 7 days of diarrhea. The standard method used to detect and isolate STEC involves sorbitol MacConkey (SMAC) agar plates that enable identification of characteristic sorbitol nonfermenting colonies of STEC O157:H7. E coli 0157:H7 does not grow on agar plates used for routine stool cultures. Notify the laboratory and request specific testing for this organism when hemolytic-uremic syndrome is suspected. Even patients with documented bloody diarrhea and other classic features of STEC-HUS often do not yield a causative organism on stool culture. This reflects the limited sensitivity of stool culture, not the absence of disease. The diagnosis of hemolytic-uremic syndrome is a clinical one and is not excluded by a negative stool culture.

Stx may be detected using specific antibody testing, gene studies, and enzyme-linked immunosorbent assay (ELISA).

Stool leukocytes have little value in detecting E coli 0157:H7. They are absent in approximately 50% of cases.

Other tests

A test for serum antibodies to STEC 0157:H7 is available, but its clinical use is not well defined.

Complement C3 may be decreased in patients with aHUS.

Genetic testing for complement factor mutations is available from a limited number of laboratories, in some cases only on a research basis. Consult with an expert in this area before ordering such tests.

Genetic tests may take weeks or months to perform, so they are not useful in the immediate management of a patient with hemolytic-uremic syndrome, and acute treatment decisions should not be delayed while awaiting results. Results may be helpful in determining long-term prognosis (eg, the presence of factor H mutations portends a very high risk of recurrence). Tests done on a fee basis may be very expensive. Tests done on a research basis require informed consent. Check with the facility regarding applicable policies for research testing.

Laboratories offering specialized genetic, ADAMTS13, and/or complement testing are listed below. This is not intended to be an exclusive listing; other laboratories may also offer these services. For additional details, contact the laboratories; information on some laboratories is also summarized in the guidelines from Ariceta et al, which is cited in the references. [6]

Service d’Immunologie Biologique

Hospital Europeén George Pompidou

20–40 rue Leblanc

75908 Paris cedex 15

France

veronique.fremeaux-bacchi@egp.aphp.fr

The Northern Genetics Service

Institute of Human Genetics

Newcastle upon Tyne Hospitals

NHS Foundation Trust

International Centre for Life

Newcastle upon Tyne NE1 3BZ

UK

lisa.strain@nuth.nhs.uk

Mario Negri Institute for Pharmacological Research

Via Gavazzeni 11

24125 Bergamo

Italy

gremuzzi@marionegri.it

noris@marionegri.it

Department of Biological Infection

Leibniz Institute for Natural Product Research and Infection Biology

Hans Knoell Institute for Natural Product Research

Beutenbergstr. 11a

07745 Jena

Germany

peter.zipfel@hki-jena.de

Department of Pediatrics

BMC C14

Lund University,

Klinikgatan 28, 22184 Lund, Sweden

diana.karpman@med.lu.se

Laboratory for Paediatrics and Neurology

Radboud University Nijmegen Medical Center

Postbus 9101

6500 HB Nijmegen

Geert Grooteplein 10 6525 GA Nijmegen

The Netherlands

B.vandenHeuvel@cukz.umcn.nl

Immunology Unit and Research Unit

Hospital Universitario La Paz

Paseo de la Castellana 261

28046 Madrid

Spain

srdecordoba@cib.csic.es

psanchez.hulp@salud.madrid.org

Laboratory of Complement Genetics

Centro de Investigaciones Biológicas

Ramiro de Maeztu 9

28040 Madrid

Spain.

srdecordoba@cib.csic.es

psanchez.hulp@salud.madrid.org

U770 INSERM

Hopital de Bicetre

80 rue du General Leclerc

94276 Le Kremlin-Bicetre cedex

France

agnes.veyradier@abc.aphp.fr

Haemostasis Research Unit

Haematology Department

University College London

1st floor

51 Chenies Mews

London WC1E 6HX

UK

i.Mackie@ucl.ac.uk

g.purdy@ucl.ac.uk

University Medical Center Hamburg-Eppendorf

Department of Pediatric Hematology and Oncology

Molecular Genetics Laboratory

Martinistrasse 52

20246 Hamburg

Germany

schneppenheim@uke.de

f.oyen@uke.de

Molecular Otolaryngology Research Laboratories

University of Iowa

Telephone: 319-335-7997

Address: 5270 CBRB Otolaryngology—Head & Neck Surgery

University of Iowa

Iowa City, Iowa 52242

E-mail: carla-nishimura@uiowa.edu

E-mail:nic-meyer@uiowa.edu

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Imaging Studies

Consider performing chest radiography to evaluate for pulmonary congestion or edema, if clinically indicated.

Renal ultrasound typically reveals nonspecific findings (eg, increased echogenicity) and is of little use. Ultrasonography may be helpful if the diagnosis is uncertain or if one needs evaluation of blood flow in the large renal vessels.

Abdominal ultrasonography or CT scanning may help if clinical findings raise suspicion of intestinal obstruction or perforation.

Noncontrast CT scanning or MRI of the head is indicated in patients with CNS symptoms or acute mental status changes. [7] Avoid iodinated contrast or gadolinium in patients with decreased renal function.

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Other Tests

Patients with hyperkalemia may require ECG monitoring.

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Histologic Findings

Renal biopsy is not usually necessary for diagnosis and may be contraindicated due to thrombocytopenia. Histologic analysis of kidney specimens reveals thrombotic microangiopathy, with swollen glomerular endothelial cells and red cells and platelets in the capillaries. Accumulation of fibrinlike material in the subendothelial space creates a thickened appearance to the capillary walls. Thrombi may be observed in the glomerular capillaries and arterioles. These findings can progress to acute cortical necrosis involving both glomeruli and convoluted tubules.

Histological slides are presented below.

Peripheral blood smear in hemolytic-uremic syndrom Peripheral blood smear in hemolytic-uremic syndrome (HUS) showing many schistocytes and RBC fragments due to hemolysis, and relatively few platelets reflective of thrombocytopenia.
Micrograph of a glomerulus in hemolytic-uremic syn Micrograph of a glomerulus in hemolytic-uremic syndrome, showing thrombi and red blood cell fragments in the capillary space. Courtesy of Xin J (Joseph) Zhou, MD, Renal Path Diagnostics, Pathologists BioMedical Labs.

Tissue section of the gut shows microangiopathy, with endothelial cell injury, and thrombosis, with submucosal edema and hemorrhage.

Microthrombi may be observed in other organs, including the lungs, liver, heart, adrenal glands, brain, thyroid, pancreas, thymus, lymph nodes, and ovaries.

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