Hemolytic-uremic syndrome
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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 |
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Overview
In medicine, hemolytic-uremic syndrome (or haemolytic-uraemic syndrome, abbreviated HUS) is a disease characterized by microangiopathic hemolytic anemia, acute renal failure and a low platelet count (thrombocytopenia).
History
- Described by Moschowitz in 1925 - disease with hyaline thrombi in many organs
- Pentad from 1964 case series of 271 published cases:
- Thrombocytopenia
- Microangiopathic hemolytic anemia
- Neurologic symptoms and signs
- Renal function abnormalities
- Fever
- When first described, >90% fatal
HUS first described in 1955 in 5 children with ARF who died with renal cortical necrosis
Epidemiology
HUS has a peak incidence between 6 months and 4 years of age.[1]
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 1990's, 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.
Molecular Biology
- Platelet-rich thrombi in affected organs (unclear etiology of tissue specificity CD36)
- vWF (endothelially synthesized) -> ULvWf multimers -> shear stress unfolds and causes massive platelet aggregation
- Normally, UlvWf digested by metalloprotease to “normal” size vWf multimers
- Familial forms of TTP lack metalloprotease activity
- Acquired forms of TTP have IgG antibody, which reduce metalloprotease activity during flares
Metalloprotease activity appears normal in HUS
- In HUS, and in cases of TTP without decreased metalloprotease activity, other etiologies of platelet activation have been proposed:
- Endothelial injury (esp. drug induced)
- Toxins (i.e. Shiga toxin)
- PAI – 1
- Other genetic factors (Factor H, Factor I deficiencies, complement derangements)
Pathophysiology & Etiology
- Childhood HUS
- After enterohemorrhagic E. Coli (usually O157:H7)
- Idiopathic
- Adult TTP-HUS
- Idiopathic
- Drug toxicity
- Immune mediated:
- MDS
- Conditioning for BMT
- Pregnancy or postpartum
- Autoimmune disease (APL syndrome, SLE, scleroderma)
- HIV/AIDS
- CMV
- Tuberculosis
- After enterohemorrhagic E. Coli
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. The only distinguishing feature is that in TTP, neurological symptoms occur more often, but this is not always the case.
Signs and symptoms
The classic childhood case of HUS occurs after bloody diarrhea caused by E. coli O157:H7, a strain of E. coli that expresses verotoxin (also called Shiga toxin). The toxin enters the bloodstream, attaches to renal endothelium and initiates an inflammatory reaction leading to acute renal failure (ARF) and disseminated intravascular coagulation (DIC). The fibrin mesh destroys red blood cells and captures thrombocytes, leading to a decrease of both on complete blood count. The usual age of onset is between 2 and adolescence.
HUS occurs after 2-7% of all E. coli O157:H7 infections.
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 cancer chemotherapy (mitomycin, cyclosporine, cisplatin and bleomycin).
A third category is referred to as familial HUS. It represents 5-10% of HUS cases and is largely due to mutations in the complement proteins factor H, membrane cofactor protein and factor I leading to uncontrolled complement system activation. Recurrent thromboses result in a high mortality rate.
Treatment
Treatment is generally supportive with dialysis as needed. Platelet transfusion may actually worsen outcome.
In severe cases or when there is diagnostic uncertainty between HUS and TTP, plasmapheresis is the treatment of choice.
Antibiotic treatment of O157:H7 colitis may stimulate further verotoxin production and thereby increase the risk of HUS.[1]
- Plasma exchange daily until LDH normal and platelets stable
- Renal pathology may not entirely resolve (no data on continued plasma exchange after plts and markers of hemolysis have resolved)
- Average 7-16 exchanges required to induce remission
- Caution plasmapheresis-associated thrombocytopenia (more with certain instruments)
- Cryopoor plasma exchange not better than regular FFP
Future or Investigational Therapies
- ASA and dipyridamole not effective alone, ? benefit when added to plasma exchange
- In poorly responsive or resistant disease, INCREASE PLASMA EXCHANGE
- Then consider:
- prednisone (1 mg/kg per day)
- methylprednisolone (125 mg IV bid)
- Vincristine
- IVIG
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%. Older children and adults have a worse prognosis.[1]
References
See also
External links
WikiDoc Research Resources for Hemolytic-uremic syndrome | |
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| Articles on Hemolytic-uremic syndrome | Most recent articles on Hemolytic-uremic syndrome • Most cited articles on Hemolytic-uremic syndrome • Review articles on Hemolytic-uremic syndrome • Articles on Hemolytic-uremic syndrome in N Eng J Med, Lancet, BMJ |
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| Evidence Based Medicine Regarding Hemolytic-uremic syndrome | Cochrane Collaboration on Hemolytic-uremic syndrome • Bandolier on Hemolytic-uremic syndrome • TRIP on Hemolytic-uremic syndrome |
| Cost Effectiveness of Hemolytic-uremic syndrome | Cost Effectiveness of Hemolytic-uremic syndrome |
| Clinical Trials Involving Hemolytic-uremic syndrome | Ongoing Trials on Hemolytic-uremic syndrome at Clinical Trials.gov • Trial results on Hemolytic-uremic syndrome • Clinical Trials on Hemolytic-uremic syndrome at Google |
| Guidelines / Policies / Government Resources (FDA/CDC) Regarding Hemolytic-uremic syndrome | US National Guidelines Clearinghouse on Hemolytic-uremic syndrome • NICE Guidance on Hemolytic-uremic syndrome • NHS PRODIGY Guidance • FDA on Hemolytic-uremic syndrome • CDC on Hemolytic-uremic syndrome |
| Textbook Information on Hemolytic-uremic syndrome | Books and Textbook Information on Hemolytic-uremic syndrome |
| Pharmacology Resources on Hemolytic-uremic syndrome | Dosing of Hemolytic-uremic syndrome • Drug interactions with Hemolytic-uremic syndrome • Side effects of Hemolytic-uremic syndrome • Allergic reactions to Hemolytic-uremic syndrome • Overdose information on Hemolytic-uremic syndrome • Carcinogenicity information on Hemolytic-uremic syndrome • Hemolytic-uremic syndrome in pregnancy • Pharmacokinetics of Hemolytic-uremic syndrome • |
| Genetics, Pharmacogenomics, and Proteinomics of Hemolytic-uremic syndrome | Genetics of Hemolytic-uremic syndrome • Pharmacogenomics of Hemolytic-uremic syndrome • Proteomics of Hemolytic-uremic syndrome |
| Newstories on Hemolytic-uremic syndrome | Hemolytic-uremic syndrome in the news • Be alerted to news on Hemolytic-uremic syndrome • News trends on Hemolytic-uremic syndrome |
| Commentary on Hemolytic-uremic syndrome | Blogs on Hemolytic-uremic syndrome |
| Patient Resources on Hemolytic-uremic syndrome | Patient resources on Hemolytic-uremic syndrome • Discussion groups on Hemolytic-uremic syndrome • Patient Handouts on Hemolytic-uremic syndrome • Directions to Hospitals Treating Hemolytic-uremic syndrome • Risk calculators and risk factors for Hemolytic-uremic syndrome |
| Healthcare Provider Resources on Hemolytic-uremic syndrome | Symptoms of Hemolytic-uremic syndrome • Causes & Risk Factors for Hemolytic-uremic syndrome • Diagnostic studies for Hemolytic-uremic syndrome • Treatment of Hemolytic-uremic syndrome |
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| Informatics Resources on Hemolytic-uremic syndrome | List of terms related to Hemolytic-uremic syndrome |
fr:Syndrome hémolytique et urémique no:Hemolytisk-uremisk syndrom nn:Hemolytisk uremisk syndromsr:Хемолитички уремијски синдром
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Acknowledgement and Attribution Regarding Sources of Content
Some of the initial content on this page may be incorporated in part from copyleft sources in the public domain including wikis such as Wikipedia and AskDrWiki. Drug information for patients came from the The National Library of Medicine. Infectious disease information may have come from the Centers for Disease Control (CDC). Differential Diagnoses are drawn from clinicians as well as an amalgamation of 3 sources: 1.The Disease Database; 2. Kahan, Scott, Smith, Ellen G. In A Page: Signs and Symptoms. Malden, Massachusetts: Blackwell Publishing, 2004:3; 3. Sailer, Christian, Wasner, Susanne. Differential Diagnosis Pocket. Hermosa Beach, CA: Borm Bruckmeir Publishing LLC, 2002:7 .
