Hemolytic uremic syndrome

Background

• 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

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

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
• Malignant hypertension
• Antiphospholipid syndrome
• Scleroderma
• Antiphospholipid Syndrome (APS)
• Paroxysmal Nocturnal Hemoglobinuria (PNH)
• 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)
• Congentital 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, thiazides/furosemide

Comparision by Etiology

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

Evaluation

• 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
• LFT
  • Increased bilirubin
• Chemistry
  • Creatinine, hyperkalemia (renal failure)

Management

• Plasma exchange (plasmapheresis)
  • Usually performed if Anuria
• Eculizumab
• 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
  • Often needed for renal failure and hyperkalemia treatment
• AVOID Antibiotics
  • May lead to worsening lysis of bacteria and further toxin release
• AVOID Antimotility agents
  • Leads to prolonged gut exposure to toxins

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

Authors

Jordan Swartz, Daniel Ostermayer, Ross Donaldson, Kevin Lu, Jesse Gentiluomo, Daniel Eggeman, Claire, Neil Young, Jonathan Osgood