This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of hemolytic uremic syndrome

Smidt-Afek, Naomi

University of Missouri: MOspace

Hemolytic Uremic Syndrome Page 1 of 5    10.23.09 Hemolytic Uremic Syndrome (HUS) Background 1. Definition  o Triad of   Hemolytic anemia (microangiopathic)  Thrombocytopenia  Renal insufficiency  Pathophysiology 1. Pathology  o Proinflammatory process, caused by bacterial toxins or intrinsic factor invasion (commonly intestinal mucosa) o Infection spreads from intestine to beef in slaughterhouses o Toxin causes end organ damage (mesangial cells, renal tubular epithelium, etc) o Prothrombotic factors cause microangiopathic hemolytic anemia (Coomb's negative) o Microthrombi, platelet aggregates leading to occlusion of renal arterioles and capillaries o Possible predisposition familial, genetic or HLA-type o 2 forms of disease   Diarrhea associated (D+)   Most common type  Most cases secondary to Shiga toxin-producing E. coli (STEC) which may be part of normal flora in cattle, but not in humans  Non-diarrhea associated (D-) 2. Incidence/prevalence  o 8% of infected children will develop HUS o Incidence higher in rural areas o Outbreaks occur in developing and developed countries 3. Risk factors  o Undercooked beef o Young age (1-10 yo) o Antibiotic use for bloody diarrhea o Anti-motility/anti-diarrheal drugs o HIV o Autoimmune dz o Pregnancy o Caring for infected cattle 4. Morbidity/mortality  o Diarrhea-induced HUS   Mortality 9%   CNS involvement correlated highly with death  ESRD 3%  Renal impairment, including hypertension 25%  Hemolytic Uremic Syndrome Page 2 of 5    10.23.09 Diagnostics 1. History and physical exam  o Prodrome   Bloody diarrhea   Mainly in children, especially when STEC as pathogen  Can be asymptomatic, esp in adults o Fever o Abdominal cramps o Classic triad (after 3-14 d)   Anemia  Thrombocytopenia  Acute renal failure (oliguria, anuria, hypertension) o Neuro Sx in 32%   Irritability, seizures, altered mental status 2. Diagnostic testing  o Stool culture for STEC o CBC o Haptoglobins (decreased) o Peripheral blood smear (fragmented RBCs, burr cells, helmet cells) o Reticulocytes (elevated) o LDH (increased) o Coomb's test (negative) o Coagulation components - PT, PTT (usually normal), fibrin degradation products (normal) o Leukocytosis o Thrombocytopenia (<150,000) o Renal function tests (azotemia) o C-reactive protein (elevated) o Urinalysis (hematuria, proteinuria or normal) 3. Diagnostic "criteria"  o Clinical triad   Microangiopathic anemia  Thrombocytopenia  Renal failure 4. Recommendation  o Stool culture for STEC while having the diarrhea stage (SOR:C)3,4   Differential Diagnosis 1. Other types of dysentery 2. Henoch-Schonlein purpura  o Renal disease o Purpura but no thrombocytopenia o Arthritis o Abdominal pain 3. DIC  o Low fibrinogen o Thrombin time prolonged o Low fibrin degradation products (FDP) Hemolytic Uremic Syndrome Page 3 of 5    10.23.09 4. TTP  o Hemolytic anemia, thrombocytopenia and CNS involvement   Occasionally renal failure, making clinical distinction difficult o Neurological changes   In 90% of TTP and 15% of HUS o Acute renal failure and anuria   In 2% of TTP and 98% of HUS o Protease activity   Decreased more in TTP (89% vs 13% in HUS) o Protease inhibitor   Exists in 51% of TTP and not in HUS o Important to distinguish TTP from HUS   TTP needs prompt plasma exchange otherwise mortality rate very high  Therapeutics 1. Acute treatment  o Do not treat with antibiotics or antidiarrheals (SOR:C)5,6  o Fluid and electrolytes   Some evidence suggests early rehydration after diarrhea and sodium replacement may prevent severe complications  Caution to avoid overload of fluids when HUS develops  Monitor fluids in/out, weight and vital signs, electrolytes o Anemia   Replace blood if H&H <6/18 o Platelets   Rarely needed, only if bleeding and <10K o Acute renal failure   Adjust medication dose  Avoid nephrotoxic medications  Restrict fluid to insensible loss plus urine output  Correct electrolytes  Consider dialysis if uremia symptoms present, severe fluid overload, electrolyte abnormalities, early dialysis related to better outcome o Hypertension   Calcium channel blockers   1st-line  Nifedipine  ACE inhibitors   2nd-line, controversial data   Enalapril  Other antihypertensives medication may be considered as well o In rare cases when there is CNS involvement, some evidence suggests use of plasmapheresis, similar to adult patients with TTP (where CNS involvement is a major manifestation) o HUS is a reportable disease   Hemolytic Uremic Syndrome Page 4 of 5    10.23.09 2. Further management  o ACE inhibitors   Recommended for long-term, but have to be watched for possible worsening renal function o Monitor platelets 3. Prevention  o Avoid ingestion of infected food   Once infection occurs, no management proven to prevent development of HUS  Follow-Up 1. Blood pressure monitoring / treatment (ACEi) 2. Renal function tests   Prognosis 1. Complications  o Gastrointestinal   Intestinal strictures/perforations  Intussusception  Pancreatitis  Severe colitis o Neurologic (rare and may confuse with TTP)   Altered mental status  Focal neurologic signs  Seizures o Renal   Chronic renal failure  Hematuria  Hypertension  Proteinuria o Cardiac   Fluid overload  Pericarditis due to uremia  Prevention  1. Avoid eating contaminated / undercooked meat (beef) 2. Avoid swimming in contaminated/dirty water 3. Wash hands  Patient Education 1. http://familydoctor.org/online/famdocen/home/common/kidney/905.printerview.html  References 1. Noris M, Remuzzi G. Hemolytic uremic syndrome. J Am Soc Nephrol 2005; 16:1035. 2. Razzaq S. Hemolytic uremic syndrome: An Emerging Health Risk. Am Fam Physician 2006; 74: 991-6 Hemolytic Uremic Syndrome Page 5 of 5    10.23.09 3. Banatyala N, Griffin PM, et al. The US national prospective hemolytic uremic syndrome study: microbiologic, serologic, clinical, and epidemiologic findings. J infect Dis 2001;183:1063-70. 4. Gerber A, Karch H, Allerberger F et al. Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients. J infect Dis 2002;186:493-500. 5. Bin Saeed AA, El Bushra HE, Al-Hamdan . Does treatment of bloody diarrhea due to Shigella dysenteriae type 1 with ampicillin precipitate hemolytic uremic syndrome? Emerg Infect Dis 1995;1:134-7. 6. Wong CS, Jelacic S et al. The risk of the hemolytic-uremic syndrome after treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342:1930-6 7. Centers for Disease Control and Prevention. Summary of notifiable diseases, United States, 1996. MMWR Morb Mortal Wkly Rep 1997; 45:1-87. 8. Chandler WL, Jelacic S, Boster DR, et al. Prothrombotic coagulation abnormalities preceding the Hemolytic –uremic syndrome. N Engl L Med 2002; 346:23-32 9. Grabowski EF,. The Hemolytic-uremic syndrome-Toxin, Thrombin, And Thrombosis. N Engl L Med 2002; 346:23-32 10. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food--selected sites, United States, 2003. MMWR Morb Mortal Wkly Rep 2004; 53:338. 11. Garg AX, Suri RS, et al. Long term renal prognosis of diarrhea associated producing hemolytic uremic syndrome: a systematic review, and meta regression. JAMA 2003;290:1360-70.   Author:  Naomi Smidt-Afek, MD, North Shore University Hospital Glen Cove, NY  Editor:  Brett White, MD, Oregon Health & Sciences University 

Hemolytic uremic syndrome (HUS)

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