Hemolytic uremic syndrome: Wikis

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Hemolytic-uremic syndrome
Classification and external resources
ICD-10 D59.3
ICD-9 283.11
OMIM 235400
DiseasesDB 13052
eMedicine ped/960
MeSH D006463

HUS was first defined as a syndrome in 1955.[1][2]

Contents

Signs and symptoms

E. coli O157:H7 increases risk of hemolytic-uremic syndrome.[3]

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Childhood HUS

HUS is part of thrombotic microangiopathies that encompass Thrombotic thrombocytopenic purpura (TTP) and HUS. The classic childhood case of HUS occurs after bloody diarrhea caused by a strain of E. coli that expresses verotoxin (also called Shiga-like toxin) which is known as SPEC (Shiga-producing E. coli) or EHEC (Enterohemorrhagic E. coli). HUS follows an influenza-like or gastrointestinal (GI) prodrome with bleeding manifestations (especially hematemesis and melena), severe oliguria, hematuria, a microangiopathic hemolytic anemia, and (in some patients) prominent neurologic changes.[4] A somewhat less common form of HUS (~10% of cases) does not follow SPEC infection and is thought to result from factor H deficiency (a complement regulatory protein) that results in uncontrolled complement activation after minor endothelial injury resulting in thrombosis.[5] In the classical form (90% of cases), the SPEC toxin enters the bloodstream, attaches to glomerular endothelium (blood vessel cell lining of kidney), causing damage to blood vessels (not just in the kidneys but in all tissues of the body), and initiates a non-inflammatory reaction leading to acute renal failure (ARF) and platelet activation that causes thrombocytopenia (low platelet count). The typical pathophysiology involves the shiga-toxin binding to proteins on the surface of glomerular endothelium and inactivating a metalloproteinase ADAMTS13 (which is also involved in TTP). Once the ADAMTS13 is disabled multimers of vWF form and initiate platelet activation and cause microthrombi formation. In contrast with typical Disseminated intravascular coagulation (DIC) seen with other causes of septicemia and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen, fibrinogen level, and assays for fibrin degradation products such as "D-Dimers", are generally normal despite the low platelet count (thrombocytopenia).

The arterioles and capillaries of the body become obscured by a resulting mesh of activated platelets which have adhered to endothelium via large multimeric vWF. As well as consuming platelets, this mesh thrombi destroys red blood cells as they squeeze through the narrowed blood vessels forming schistocytes (sheared RBC's) (which is a prominent feature used for diagnosis). This mechanism known as "microangiopathic hemolysis" which has been likened to the effect of a cheesewire or garotte across the vessel lumen. This can lead to severe thrombocytopenia. As in the related condition thrombotic thrombocytopenic purpura (TTP), reduced blood flow through the narrowed blood vessels of the microvascular leads to reduced blood flow to vital organs and ischemia may develop. As the kidneys and the central nervous system (brain and spinal cord) are the parts of the body most critically dependent on high blood flow, they are the most likely organs to be affected. However, in comparison to TTP, the kidneys tend to be more severely affected in HUS, and the central nervous system is less commonly affected. The usual age of onset is between 2 years and adolescence. Grossly, the kidneys may show patchy or diffuse renal cortical necrosis. Histologically, the glomeruli show thickened and sometimes split capillary walls due largely to endothelial swelling. Large deposits of fibrin-related materials in the capillary lumens, subendothelially, and in the mesangium are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi.[6]

HUS occurs after 2-7% of all E. coli O157:H7 infections.

Adult HUS

Adult HUS has similar symptoms and pathology but is an uncommon outcome of the following: HIV; antiphospholipid syndrome (associated with Lupus erythematosus and generalized hypercoagulability); post partum renal failure; malignant hypertension; scleroderma; and certain drugs including some chemotherapy drugs and other immunosuppressive agents (mitomycin, ciclosporin, cisplatin and bleomycin).

Familial HUS

A third category is referred to as familial HUS.

It represents 5-10% of HUS cases[citation needed] and is largely due to mutations in the complement proteins factor H, membrane cofactor protein and factor I[7] leading to uncontrolled complement system activation.

Recurrent thromboses result in a high mortality rate.

Diagnosis

Clinically, HUS can be very hard to distinguish from thrombotic thrombocytopenic purpura (TTP). The laboratory features are almost identical, and not every case of HUS is preceded by diarrhea. HUS is characterized by the triad of hemolytic anemia, thrombocytopenia, and acute renal failure. The only distinguishing feature is that in TTP, fever and neurological symptoms are often present; but this is not always the case.

The two conditions are sometimes treated as a single entity called "TTP/HUS".[8][9] However, some dispute this grouping, and TTP is now known to be caused by an acquired defect in the protein ADAMTS13.[10]

Treatment

Antibiotic treatment of E. coli O157:H7 colitis may stimulate further verotoxin production and thereby increase the risk of HUS.[11][12]

Treatment is generally supportive with dialysis as needed. However untreated HUS in adults may progress to end organ damage. Platelet transfusion may actually worsen outcome.

In most children with post-diarrheal HUS, there is a good chance of spontaneous resolution and hence observation in hospital is often all that is necessary, with supportive care such as hemodialysis where indicated. In children with neurological or other non-renal involvement, and in adult cases particularly when there is diagnostic uncertainty between HUS and TTP, plasmapheresis ("plasma exchange") is the treatment of choice. This is generally performed daily until the platelet count is normal, using fresh frozen plasma as the replacement fluid for the patient's plasma which is removed. Plasmapheresis may reverse the ongoing platelet consumption.

Prognosis

With aggressive treatment > 90% survive acute phase. About 9% may develop end stage renal disease. About one-third of persons with hemolytic-uremic syndrome have abnormal kidney function many years later, and a few require long-term dialysis. Another 8% of persons with hemolytic uremic syndrome have other lifelong complications, such as high blood pressure, seizures, blindness, paralysis, and the effects of having part of their colon removed. The overall mortality rate from HUS is 5-15%. Children and the elderly have a worse prognosis.[13]

Epidemiology

HUS has a peak incidence between 6 months and 4 years of age.[14]

HUS and the E. coli infections which caused it have been the source of much negative publicity for the Food and Drug Administration (FDA), meat industries, and fast-food restaurants since the 1990s, especially in the Jack in the Box contaminations. It was also featured in the Robin Cook novel Toxin. In 2006, an epidemic of harmful E. coli emerged in the United States due to contaminated spinach. 183 known cases have been reported, including 29 cases of HUS. In June, 2009, Nestle Toll House "cookie dough" was linked to an outbreak of E. coli 0157:H7 in the United States, which sickened 70 people in 30 states.[1]

See also

References

  1. ^ Anagnou NP, Papanicolaou N, Fessas P (1991). "Recurrent attacks of hemolytic uremic syndrome". Haematologia (Budap) 24 (2): 101–5. PMID 1816053. 
  2. ^ GAsser C, Gautier E, Steck A, Siebenmann RE, Oechslin R (September 1955). "Hemolytic-uremic syndrome: bilateral necrosis of the renal cortex in acute acquired hemolytic anemia" (in German). Schweiz Med Wochenschr 85 (38-39): 905–9. PMID 13274004. 
  3. ^ Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI (June 2000). "The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections". N. Engl. J. Med. 342 (26): 1930–6. doi:10.1056/NEJM200006293422601. PMID 10874060. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=10874060&promo=ONFLNS19. 
  4. ^ Robbins Basic Pathology, 7th edition
  5. ^ Kumar et al., Robbins Basic Pathology, 8th Edition; ISBN 978-1-4160-2973-1
  6. ^ Robbins Basic Pathology, 7th edition
  7. ^ Esparza-Gordillo J, Goicoechea de Jorge E, Buil A, et al. (March 2005). "Predisposition to atypical hemolytic uremic syndrome involves the concurrence of different susceptibility alleles in the regulators of complement activation gene cluster in 1q32". Hum. Mol. Genet. 14 (5): 703–12. doi:10.1093/hmg/ddi066. PMID 15661753. http://hmg.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=15661753. 
  8. ^ Coppo P, Bussel A, Charrier S, et al. (January 2003). "High-dose plasma infusion versus plasma exchange as early treatment of thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome". Medicine (Baltimore) 82 (1): 27–38. doi:10.1097/00005792-200301000-00003. PMID 12544708. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0025-7974&volume=82&issue=1&spage=27. 
  9. ^ Medina PJ, Sipols JM, George JN (September 2001). "Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome". Curr. Opin. Hematol. 8 (5): 286–93. doi:10.1097/00062752-200109000-00004. PMID 11604563. http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1065-6251&volume=8&issue=5&spage=286. 
  10. ^ Hosler GA, Cusumano AM, Hutchins GM (July 2003). "Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome are distinct pathologic entities. A review of 56 autopsy cases". Arch. Pathol. Lab. Med. 127 (7): 834–9. PMID 12823037. http://journals.allenpress.com/jrnlserv/?request=get-abstract&issn=0003-9985&volume=127&page=834. 
  11. ^ eMedicine - Hemolytic Uremic Syndrome : Article by William Shapiro
  12. ^ Panos GZ, Betsi GI, Falagas ME (September 2006). "Systematic review: are antibiotics detrimental or beneficial for the treatment of patients with Escherichia coli O157:H7 infection?". Aliment. Pharmacol. Ther. 24 (5): 731–42. doi:10.1111/j.1365-2036.2006.03036.x. PMID 16918877. http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=0269-2813&date=2006&volume=24&issue=5&spage=731. 
  13. ^ Chu P, Hemphill RR (2004). "222: Acuired hemolytic anemia". in Tintinalli JE, Kelen GD, Stapczynski JS. Emergency Medicine: A Comprehensive Study Guide (6th ed.). New York, NY: McGraw-Hill.  ISBN 0-07-138875-3
  14. ^ Corrigan JJ, Boineau FG (November 2001). "Hemolytic-uremic syndrome". Pediatr Rev 22 (11): 365–9. PMID 11691946. 

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