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
- Typical
- Occurs 2-14d after development of infectious diarrhea (bloody, no fever)
- Atypical
Clinical Features
- Consider in any child with diarrheal illness (especially bloody) with renal dysfunction
Triad
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)
Diagnosis
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
- 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
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
- ↑ Niaudet P, Boyer OG. Overview of hemolytic uremic syndrome in children. Post TW, ed. UpToDate. UpToDate Inc. Accessed February 1st, 2021.