Pediatric Hemolytic Uremic Syndrome Workup

  • Author: Robert S Gillespie, MD, MPH; Chief Editor: Craig B Langman, MD   more...
 
Updated: Sep 26, 2011
 

Laboratory Studies

  • Hematology
    • Classic findings in hemolytic-uremic syndrome (HUS) include anemia and thrombocytopenia, with fragmented RBCs (eg, schistocytes, helmet cells, burr cells).Peripheral blood smear in hemolytic-uremic syndromPeripheral blood smear in hemolytic-uremic syndrome (HUS) showing many schistocytes and RBC fragments due to hemolysis, and relatively few platelets reflective of thrombocytopenia.
    • WBC differential may reveal a left shift (ie, immature WBCs, including bands, myelocytes, metamyelocytes). Patients with diarrhea-associated hemolytic-uremic syndrome (D+ HUS) may have extremely high WBC counts, in the range of 50-60,000/mcL.
    • 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 due to vomiting, diarrhea, dehydration and renal failure; these may include hyponatremia, hyperkalemia, hyperphosphatemia, hypocalcemia, and acidosis. Phosphorous concentration is elevated.
    • Uric acid level may be increased because of acute renal failure, dehydration, and cell breakdown.
    • Protein and albumin levels may be mildly decreased.
    • Bilirubin and aminotransferase levels are typically elevated.
    • Lactate dehydrogenase (LDH) level is elevated. Serial measurements of LDH help track the approximate level of hemolytic activity.
  • Urinalysis
    • Protein
    • Heme
    • Bilirubin
    • RBCs (dysmorphic)
    • WBCs
    • Casts - Cellular, granular, pigmented, hyaline
  • Stool testing
    • Culture: Usually, culture yield is low after 7 days of diarrhea. The standard method used to detect and isolate Shigella toxin (Stx)–producing E coli (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 D+ hemolytic-uremic syndrome 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 genetic forms of hemolytic-uremic syndrome.
    • Genetic testing for complement factor mutations is available from a limited number of laboratories, in some cases only on a research basis. For a list of some laboratories offering such testing see Special Concerns. 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 poor renal prognosis).
      • 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.
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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.
  • Non-contrast CT scanning or MRI of the head is indicated in patients with CNS symptoms or acute mental status changes. Avoid iodinated contrast or gadolinium in patients with decreased renal function.
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Other Tests

  • Patients with hyperkalemia may require EKG 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.Peripheral blood smear in hemolytic-uremic syndromPeripheral blood smear in hemolytic-uremic syndrome (HUS) showing many schistocytes and RBC fragments due to hemolysis, and relatively few platelets reflective of thrombocytopenia.
  • 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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Contributor Information and Disclosures
Author

Robert S Gillespie, MD, MPH  Department of Pediatrics, Cook Children's Medical Center

Robert S Gillespie, MD, MPH is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, and Texas Medical Association

Disclosure: Nothing to disclose.

Coauthor(s)

Craig S Wong, MD, MPH  Assistant Professor, Division of Pediatric Nephrology, Department of Pediatrics, University of New Mexico School of Medicine; Director of Pediatric Kidney Transplantation, Division of Pediatric Nephrology, Department of Pediatrics, University of New Mexico Transplant Services, Children's Hospital of New Mexico

Craig S Wong, MD, MPH is a member of the following medical societies: American Society of Nephrology and American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Ronald D Prauner  MD, Assistant Professor of Pediatrics, F Edward Herbert School of Medicine, Uniformed Services of the Health Sciences; Assistant Deputy Commander for Medicine; Fort Belvoir Community Hospital, Fort Belvoir, VA; Consultant to the Army Surgeon General for Pediatric Subspecialties; Staff Pediatric Hematologist-Oncologist, Fort Belvoir Community Hospital

Ronald D Prauner is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and Christian Medical & Dental Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Richard Neiberger, MD, PhD  Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group

Disclosure: The Osler Institute Honoraria Speaking and teaching

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Luther Travis, MD  Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine

Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, and Texas Pediatric Society

Disclosure: Nothing to disclose.

Howard Trachtman, MD  Program Director, Pediatrics Research, Schneider Children's Hospital, Department of Pediatrics, Division of Nephrology, Professor, Albert Einstein College of Medicine

Howard Trachtman, MD is a member of the following medical societies: American Society of Hypertension, American Society of Nephrology, American Society of Pediatric Nephrology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD  The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, Children's Memorial Hospital

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: Merck Grant/research funds None; NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Additional Contributors

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tamara Biega, MD, to the original writing and development of this article.

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