Acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia, associated with diarrhea.
Thrombocytopenia secondary to platelet activation and consumption.
It is a non autoimmune process.
One of the thrombotic microangiopathies, along with thrombotic thrombocytopenia purpura, and preeclampsia.
Acute renal failure secondary to vascular damage.
In contrast to thrombotic thrombocytopenic purpura, renal failure is the predominant organ manifestation with neurologic symptoms and signs less common.
Differentiation from thrombotic thrombocytopenic purpura can be difficult.
In HUS of fiber rich, microthrombi dominate and thrombocytopenia is defined as platelet count less than 150,000 or less than 25% of baseline.
Catastrophic atypical HUS can occur even with normal platelet counts.
Approximately half of patients require dialysis during acute process, but most recover their renal function.
Hemolysis secondary to mechanical injury to red blood cells.
Associated with familial forms, pregnancy related diseases, toxin associated disease, chemotherapy and cancer associated therapy.
Majority of cancer-associated disease related to adenocarcinomas.
Associated primarily with mitomycin chemotherapy but also reported to be related to 5 FU, bleomycin and cis-platinum therapy.
Typically develops after a prodromal diarrheal illness-diarrhea associated hemolytic uremic syndrome.
Shiga toxin producing strains of Escherichia coli predominant etiology of HUS in children.
90% of cases associated with Shiga toxin producing organisms in children, and alternative complement pathway dysregulation accounts for an additional 6% of cases (Besbas N et al).
Diarrhea associated with hemolytic-uremic syndrome and neurologic complications is generally related to E. Coli that produce Shiga toxin (Kaper JB et al).
Shiga toxin mediated endothelial cell damage causes thrombotic occlusion of capillaries leading to acute renal failure, and severe CNS symptoms including coma, seizures or stroke.
A higher percentage of patients with CNS symptoms die or develop permanent end-stage renal disease.
Most cases of diarrhea caused by Shiga toxin producing E coli.O157:H7 (STEC).
HUS develops in 15 to 20% of infected children, with the greatest risk among those who were younger than five years of age.
HUS almost always manifest between days five and 14 of illness.
Rapid and progressive thrombocytopenia is the sentinel and universal hematologic abnormality in patients with HUS and as often accompanied by hemoglobin-uria and elevated serum LDH.
Early plasma exchange might ameliorate the course of diarrhea associated with hemolytic uremic syndrome in adults(Colic E et al).
Shiga toxin producing E. coli O104:H4 infections in northern Germany in 2011 was associated with HUS in more than 800 patients, with about 30% of patients developing neurologic complications ranging from delirium to status epilepticus.
Diarrhea associated hemolytic uremic syndrome is the most common cause of acute renal failure in previously healthy children in the U.S.
About 40% of children require temporary dialysis, up to 20% develop serious extrarenal events, and the mortality rate is 3-5%.
During outbreaks of diarrhea associated-HUS mortality is high, with a review of 49 studies-12% of patients died in the developed and stage renal disease.
More than 85% of cases are typical and are preceded by diarrhea caused by E. Coli producing Shigella like toxins with proinflammatory and prothrombotic effects on the vascular endothelium.
Very rare in adults-0.5-2.1 cases per 100,000 people per year, but is more frequent in children 6.1 cases per 100,000 children younger than 5 years per year.
Most cases of typical HUS have a good prognosis with 25% of patients have residual renal dysfunction.
Peak incidence in children is in those younger than five years of age.
Neurologic sequelae is rare.
In children neurologic manifestations tend to occur early and within the first week of diarrheal illness.
Complement activity is increased in HUS and potentiates thrombosis in brain microvasculature.
Shigella toxin induces neuronal apoptosis by up regulation of inflammatory cytokines in glial cells.
The atypical form is not associated with shiga toxin producing bacteria and may be familial or sporadic.
Atypical forms tend to recur and usually follows an aggressive course.
About 50% of patients with atypical disease develop end-stage renal failure and 25% die as a result.
Atypical disease associated with uncontrolled complement activation (Jokiranta).
Atypical hemolytic uremic syndrome is a genetic and progressive inflammatory disease that affects patients of all ages.
Atypical hemolytic-uremic syndrome is caused by defects in the complement system regulation.
Defects in the atypical hemolytic uremic syndrome are inherited, acquired, or both.
In the atypical hemolytic uremic syndrome there is chronic, uncontrolled activation of the complement system leading to platelet, leukocyte, and endothelial cell activation, and a systemic thrombotic microangiopathy.
Affected individuals have lifelong risk of systemic clinical manifestations of thrombotic mileage microangiopathy, including damage to CNS, kidneys, heart, and gastrointestinal tract.
Regulation of the complement system in atypical hemolytic uremic syndrome may be acquired, or inherited, resulting in chronic uncontrolled activation of the complement system with platelet, leukocyte, and endothelial cell activation and systemic thrombotic microangiopathy.
Patients with atypical hemolytic uremic syndrome have a lifelong risk of systemic clinical complications from thrombotic microangiopathy, including damage to multiples organ systems including the CNS, kidneys, heart, and G.I. tract.
Atypical uremic syndrome is a genetic, life-threatening, chronic disease of complement mediated thrombotic microangiopathy.
ADAMTS13 activities often reduced from the normal range of 67 to 120%, but it typically remains greater than 5 to 10%.
Plasma exchange or plasma infusion may transiently maintain normal levels of hematologic measures, but does not treat the underlying systemic disease.
It is a progressive inflammatory process that affects patients of all ages.
Plasma exchange or infusions to manage atypical hemolytic uremic syndrome may provide transient normalization of the platelet count and LDH levels in some patients, however the underlying complement dysregulation and thrombotic microangiopathy processes are likely to persist.
End-stage renal disease or death occurs in approximately 33-40% of patients during the initial clinical manifestations of atypical hemolytic uremic syndrome.
Within one year of the diagnosis of atypical hemolytic uremic syndrome up to 65% of patients treated with plasma exchange or plasma infusions develop permanent real damage, progress to end-stage renal disease or die (Caprioli J et al).
Among patients with atypical hemolytic uremic syndrome that undergo renal transplant, graft failure occurs in 60-90% of patients within one year.
In children supportive care is the current management, since plasma infusion, plasmapheresis, intravenous IgG, fibrinolytic agents, antiplatelet drugs, steroids and antioxidants have been ineffective in controlled trials.
Non-Shiga toxin associated disease has a clinical outcome which is unfavorable with up to 50% of cases progressing to renal failure and 25% dying during the acute illness.