Hemolytic uremic syndrome

Background

Schistocytes as seen in a person with hemolytic–uremic syndrome.

• Abbreviation: HUS
• Similar to TTP (which is more common in adults), but associated with less central nervous system and more renal involvement.
• Most cases occur in children <10yr (⅔ of cases in < 5yr)
• 80-90% cases due to E. coli O157:H7 infection
• Shiga toxin may induce autoantibody to CD36 (found on endothelial cells and platelets)
• May also be caused by shigella, yersinia, campylobacter, salmonella

Types

1. Typical
   • Occurs 2-14d after development of infectious diarrhea (bloody, no fever)
2. Atypical
   • Occurs in older children and adults
   • Extrarenal involvement is common (difficult to distinguish from TTP)
   • May be caused by atypical pathogens (EBV, S. pneumo) or immunosuppression

Clinical Features

• Consider in any child with diarrheal illness (especially bloody) with renal dysfunction

Triad

1. Acute renal failure
2. Thrombocytopenia
3. Microangiopathic Hemolytic Anemia (MAHA)

Other Associated Conditions

• Enteritis
• Nausea/vomiting, diarrhea (usually bloody), +/- fever
• Hyperglycemia
  • Pancreatic beta-cell death due to microthrombi within pancreas

Differential Diagnosis

• Gastroenteritis
• Appendicitis
• Colitis
• Intussusception
• IBD
• Perforation
• SLE

Causes of Glomerulonephritis

• Poststreptococcal glomerulonephritis
• Hemolytic-uremic syndrome
• Henoch-Schonlein purpura
• IgA nephropathy
• Lupus nephritis
• Alport syndrome
• Goodpasture syndrome
• Paraneoplastic

Microangiopathic Hemolytic Anemia (MAHA)

• Disseminated Intravascular Coagulation (DIC)
• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome (HUS)
• HELLP syndrome
• Heparin-Induced Thrombocytopenia (HIT)
• Hereditary spherocytosis
• Paroxysmal nocturnal hemoglobinuria (PNH)
• Malignant hypertension
• Scleroderma
• Antiphospholipid Syndrome (APS)
• Other medical causes: malignancy, renal allograft rejection, vasculitides like polyarteritis nodosa and Wegener's granulomatosis
• Drugs: chemotherapy; Clopidogrel (Plavix) associated with TTP
• Nonvascular causes: prosthetic valve (more common with mechanical, more common at aortic valve), LVAD, TIPS, coil embolization, patched AV shunt, AVM

Thrombocytopenia

Decreased production

• Marrow infiltration (tumor or infection)
• Viral infections (rubella, HIV)
• Marrow suppression (commonly chemotherapy or radiation)
• Congenital thrombocytopenia
  • Fanconi anemia
  • Alport syndrome
  • Bernand Soulier
• Vitamin B12 and/or folate deficiency

Increased platelet destruction or use

• Idiopathic thrombocytopenic purpura
• Thrombotic Thrombocytopenic Purpura (TTP)
• Hemolytic Uremic Syndrome (HUS)
• Disseminated Intravascular Coagulation (DIC)
• Viral infections (HIV, mumps, varicella, EBV)
• Drugs (heparin, protamine)
• Postransfusion or Posttransplantation
• Autoimmune destruction (SLE or Sarcoidosis)
• Mechanical destruction
  • Artificial valves
  • ECMO
• HELLP syndrome
• Excessive hemorrhage
• Hemodialysis, extracorporeal circulation
• Splenic Sequestration
  • Occurs in Sickle cell disease and Cirrhosis

Drug Induced

• sulfa antibiotics, ETOH, ASA, thiazide diuretics/furosemide

Comparison by Etiology

	ITP	TTP	HUS	HIT	DIC
↓ PLT	Yes	Yes	Yes	Yes	Yes
↑PT/INR	No	No	No	+/-	Yes
MAHA	No	Yes	Yes	No	Yes
↓ Fibrinogen	No	No	No	No	Yes
Ok to give PLT	Yes	No	No	No	Yes

Evaluation

Workup

• CBC
  • Anemia
  • Thrombocytopenia
  • Peripheral smear checking for schistocytes, burr cells, helmet cells, spherocytes and segmented red blood cells
• LDH (elevated)
• Haptoglobin (decreased)
• Reticulocyte count (appropriate)
• PT/PTT/INR (normal; differentiates from DIC)
• Stool tests
  • Shiga toxin, E. coli O157:H7 test
• Urinalysis
  • Hematuria, casts
• LFTs
  • Increased bilirubin
• Chemistry
  • Creatinine elevation (often more pronounced than TTP), uremia, hyperkalemia (renal failure)

Management

• Initial management largely supportive with early fluid resuscitation
• Insulin therapy if hyperglycemic and ketones (pancreatic insufficiency complication)
• Antihypertensives
  • NifedipineER (0.25-0.5 mg/kg/day oral)
  • Labetalol 1-3 mg/kg/day, divided into twice daily dosing (12 mg/kg/day up to 1200 mg/day)
  • Nitroprusside 0.3-0.5 ug/kg/min IV (max 10 ug/kg/min)
• Plasma exchange (plasmapheresis)
  • Usually performed if anuria or neurologic sequela
• Eculizumab
  • Monoclonal anti-C5 antibody that interrupts complement cascade. Shown to be effective in cases of atypical HUS (those not due to shiga toxin forming bacteria).
• Transfusion of RBCs(only severe bleeding)
  • Generally only indicated if plasma exchange cannot be performed immediately
• Platelet transfusion is AVOIDED
  • Only used for life-threatening bleeding or intracranial hemorrhage under guidance from hematologist
  • Platelet infusion may lead to acutely worsened thrombosis, renal failure, and death
• Hemodialysis/Hemoperfusion
  • Usually reserved for symptomatic uremia, azotemia (BUN >80 mg/dL), fluid overload or electrolyte abnormalities refractory to medical therapy
• AVOID Antibiotics
  • May lead to worsening lysis of bacteria and further shiga toxin release
• AVOID Antimotility agents
  • Leads to prolonged gut exposure to toxins
  • Risk of toxic megacolon

Disposition

• Admit

See Also

• TTP

References

• Corrigan J. Boineau FG. Hemolytic-uremic syndrome. Pediatr Rev. Nov 2001;22(11):365-9
• George J. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006; 354:1927