Hemolytic-uremic syndrome
Encyclopedia
Hemolytic-uremic syndrome (or haemolytic-uraemic syndrome), abbreviated HUS, is a disease characterized by hemolytic anemia
, acute renal failure
(uremia
) and a low platelet
count (thrombocytopenia
). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of diarrhea
caused by E. coli O157:H7
, which is acquired as a foodborne illness
. It is a medical emergency
and carries a 5–10% mortality; of the remainder, the majority recover without major consequences but a small proportion develop chronic kidney disease and become reliant on renal replacement therapy
. HUS was first defined as a syndrome
in 1955.
In May, 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4 contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 4000 cases, with hemolytic-uremic syndrome developing in more than 800 of the cases, with 50 of them resulting in death. Over 90% of the cases were in adults.
, a category of disorders that includes thrombotic thrombocytopenic purpura
(TTP).
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 shiga toxin-producing E. coli (STEC) or enterohemorrhagic E. coli (EHEC). 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.
A somewhat less common form of HUS (~10% of cases) does not follow STEC 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
.
In the classical form (90% of cases), the STEC toxin enters the bloodstream and causes damage to the body's vascular endothelium. This is especially damaging to the kidney, where the toxin attaches to the glomerular endothelium and initiates a noninflammatory reaction leading to acute renal failure
. Moreover, the generalized endothelial damage leads to platelet
activation that causes thrombocytopenia
(low platelet count). The renal glomerular endothelial cells express a receptor for the toxin.
The typical pathophysiology involves the shiga-toxin binding to proteins on the surface of glomerular endothelium and inactivating a metalloproteinase
called ADAMTS13
, which is also involved in the closely related thrombotic thrombocytopenic purpura
(TTP). Once the ADAMTS13 is disabled, multimers of von Willebrand Factor
(vWF) form and initiate platelet activation and cause microthrombi formation. Inhibition of ADAMTS13 causes activated platelets because the large multimers of uncleaved vWF are hyperactive. The arterioles and capillaries of the body become obstructed by the resulting complexes of activated platelets which have adhered to endothelium via large multimeric vWF. The growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. This mechanism, known as microangiopathic hemolysis
, has been likened to the effect of a cheesewire or garotte across the vessel lumen
. The presence of schistocytes is a key finding that helps to diagnose HUS.
The consumption of platelets as they adhere to the thrombi lodged in the small vessels can lead to severe thrombocytopenia.
As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature
leads to reduced blood flow to vital organs, and ischemia
may develop. The kidneys and the central nervous system
(brain and spinal cord) are the parts of the body most critically dependent on high blood flow, thus 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.
In contrast with typical disseminated intravascular coagulation
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).
HUS occurs after 2-7% of all E. coli O157:H7 infections. Children and adolescents are commonly affected. 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.
; antiphospholipid syndrome (associated with lupus erythematosus
and generalized hypercoagulability); postpartum renal failure; malignant hypertension
; scleroderma
; and certain drugs, including some chemotherapy
drugs and other immunosuppressive agents (mitomycin
, ciclosporin
, cisplatin
and bleomycin
).
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.
Most reported HUS cases during the 2011 Escherichia coli O104:H4 outbreak were atypical cases.
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.
A pericardial friction rub can also sometimes be heard on auscultation (uremic pericarditis).
The two conditions are sometimes treated as a single entity called TTP/HUS. However, some dispute this grouping, and TTP is now known to be caused by an acquired defect in the protein ADAMTS13
.
Treatment is generally supportive, with dialysis
as needed. Untreated HUS in adults, however, may progress to end-stage organ damage
. Platelet
transfusion
may actually worsen the outcome.
Since 2010, eculizumab
has been used experimentally in the treatment of HUS, following approval from the European Medicines Agency in 2007 for the treatment of paroxysmal nocturnal hemoglobinuria.
In most children with postdiarrheal HUS, there is a good chance of spontaneous resolution, so observation in a hospital is often all that is necessary, with supportive care such as hemodialysis
where indicated. In children with neurological or other nonrenal 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.
. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizure
s, 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.
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
. The known cases have been reported at 183, 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.http://www.cnn.com/2009/HEALTH/06/22/cookie.dough.ecoli/index.html
At least 29 people died presumably from hemolytic-uremic syndrome in the 2011 E. coli O104:H4 outbreak in Europe.
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
, acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
(uremia
Uremia
Uremia or uraemia is a term used to loosely describe the illness accompanying kidney failure , in particular the nitrogenous waste products associated with the failure of this organ....
) and a low platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
count (thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
caused by E. coli O157:H7
Escherichia coli O157:H7
Escherichia coli O157:H7 is an enterohemorrhagic strain of the bacterium Escherichia coli and a cause of foodborne illness. Infection often leads to hemorrhagic diarrhea, and occasionally to kidney failure, especially in young children and elderly persons...
, which is acquired as a foodborne illness
Foodborne illness
Foodborne illness is any illness resulting from the consumption of contaminated food, pathogenic bacteria, viruses, or parasites that contaminate food, as well as chemical or natural toxins such as poisonous mushrooms.-Causes:Foodborne illness usually arises from improper handling, preparation, or...
. It is a medical emergency
Medical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
and carries a 5–10% mortality; of the remainder, the majority recover without major consequences but a small proportion develop chronic kidney disease and become reliant on renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
. HUS was first defined as a syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
in 1955.
In May, 2011 an epidemic of bloody diarrhea caused by E. coli O104:H4 contaminated fenugreek seeds hit Germany. Tracing the epidemic revealed more than 4000 cases, with hemolytic-uremic syndrome developing in more than 800 of the cases, with 50 of them resulting in death. Over 90% of the cases were in adults.
In children
HUS is one of the thrombotic microangiopathiesThrombotic microangiopathies
Thrombotic microangiopathy, abbreviated TMA, is a pathology that results in thrombosis in capillaries and arterioles, due to an endothelial injury. It may be seen in association with thrombocytopenia, anemia, purpura and renal failure....
, a category of disorders that includes thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
(TTP).
The classic childhood case of HUS occurs after bloody diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
caused by a strain of E. coli that expresses verotoxin (also called shiga-like toxin
Shiga-like toxin
Shiga-like toxin, also known as verotoxin, is a toxin generated by some strains of Escherichia coli . It is named for its similarity to the AB5-type Shiga toxin produced by the bacteria Shigella dysenteriae....
) which is known as shiga toxin-producing E. coli (STEC) or enterohemorrhagic E. coli (EHEC). HUS follows an influenza-like or gastrointestinal (GI) prodrome
Prodrome
In medicine, a prodrome is an early symptom that might indicate the start of a disease before specific symptoms occur. It is derived from the Greek word prodromos or precursor...
with bleeding manifestations (especially hematemesis
Hematemesis
Hematemesis or haematemesis is the vomiting of blood. The source is generally the upper gastrointestinal tract. Patients can easily confuse it with hemoptysis , although the latter is more common.-Signs:...
and melena
Melena
In medicine, melena or melaena refers to the black, "tarry" feces that are associated with gastrointestinal hemorrhage. The black color is caused by oxidation of the iron in hemoglobin during its passage through the ileum and colon.-Melena vs...
), severe oliguria
Oliguria
Oliguria is the low output of urine, It is clinically classified as an output below 300-500ml/day. The decreased output of urine may be a sign of dehydration, renal failure, hypovolemic shock, HHNS Hyperosmolar Hyperglycemic Nonketotic Syndrome, multiple organ dysfunction syndrome, urinary...
, hematuria
Hematuria
In medicine, hematuria, or haematuria, is the presence of red blood cells in the urine. It may be idiopathic and/or benign, or it can be a sign that there is a kidney stone or a tumor in the urinary tract , ranging from trivial to lethal...
, a microangiopathic hemolytic anemia
Microangiopathic hemolytic anemia
In medicine microangiopathic hemolytic anemia is a microangiopathic subgroup of hemolytic anemia caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.-Presentation:It is referred as Runner's anemia...
, and (in some patients) prominent neurologic changes.
A somewhat less common form of HUS (~10% of cases) does not follow STEC infection and is thought to result from factor H
Factor H
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...
deficiency (a complement regulatory protein) that results in uncontrolled complement activation after minor endothelial
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
injury resulting in thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
.
In the classical form (90% of cases), the STEC toxin enters the bloodstream and causes damage to the body's vascular endothelium. This is especially damaging to the kidney, where the toxin attaches to the glomerular endothelium and initiates a noninflammatory reaction leading to acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
. Moreover, the generalized endothelial damage leads to platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
activation that causes thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
(low platelet count). The renal glomerular endothelial cells express a receptor for the toxin.
The typical pathophysiology involves the shiga-toxin binding to proteins on the surface of glomerular endothelium and inactivating a metalloproteinase
Metalloproteinase
Metalloproteinases constitute a family of enzymes from the group of proteases, classified by the nature of the most prominent functional group in their active site. These are proteolytic enzymes whose catalytic mechanism involves a metal. Most metalloproteases are zinc-dependent, but some use...
called ADAMTS13
ADAMTS13
ADAMTS13 —also known as von Willebrand factor-cleaving protease —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor , a large protein involved in blood clotting...
, which is also involved in the closely related thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura
Thrombotic thrombocytopenic purpura is a rare disorder of the blood-coagulation system, causing extensive microscopic thromboses to form in small blood vessels throughout the body...
(TTP). Once the ADAMTS13 is disabled, multimers of von Willebrand Factor
Von Willebrand factor
von Willebrand factor is a blood glycoprotein involved in hemostasis. It is deficient or defective in von Willebrand disease and is involved in a large number of other diseases, including thrombotic thrombocytopenic purpura, Heyde's syndrome, and possibly hemolytic-uremic syndrome...
(vWF) form and initiate platelet activation and cause microthrombi formation. Inhibition of ADAMTS13 causes activated platelets because the large multimers of uncleaved vWF are hyperactive. The arterioles and capillaries of the body become obstructed by the resulting complexes of activated platelets which have adhered to endothelium via large multimeric vWF. The growing thrombi lodged in smaller vessels destroy red blood cells (RBCs) as they squeeze through the narrowed blood vessels, forming schistocytes, or fragments of sheared RBCs. This mechanism, known as microangiopathic hemolysis
Microangiopathic hemolytic anemia
In medicine microangiopathic hemolytic anemia is a microangiopathic subgroup of hemolytic anemia caused by factors in the small blood vessels. It is identified by the finding of anemia and schistocytes on microscopy of the blood film.-Presentation:It is referred as Runner's anemia...
, has been likened to the effect of a cheesewire or garotte across the vessel lumen
Lumen (anatomy)
A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...
. The presence of schistocytes is a key finding that helps to diagnose HUS.
The consumption of platelets as they adhere to the thrombi lodged in the small vessels can lead to severe thrombocytopenia.
As in the related condition TTP, reduced blood flow through the narrowed blood vessels of the microvasculature
Microvessel
Microvessel or microvasculature can refer to:* Arteriole, a small diameter blood vessel that extends and branches out from an artery and leads to capillaries* Capillary, the smallest blood vessels...
leads to reduced blood flow to vital organs, and ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
may develop. The kidneys and the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
(brain and spinal cord) are the parts of the body most critically dependent on high blood flow, thus 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.
In contrast with typical disseminated intravascular coagulation
Disseminated intravascular coagulation
Disseminated intravascular coagulation , also known as disseminated intravascular coagulopathy or consumptive coagulopathy, is a pathological activation of coagulation mechanisms that happens in response to a variety of diseases. DIC leads to the formation of small blood clots inside the blood...
seen with other causes of septicemia and occasionally with advanced cancer, coagulation factors are not consumed in HUS (or TTP) and the coagulation screen
Coagulation screen
A combination of screening laboratory tests, designed to provide rapid non-specific information, which allows an initial broad categorization of haemostatic problems.The basic screen consists of:* platelet count* bleeding time for platelet function...
, fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...
level, and assays for fibrin degradation products such as "D-Dimers
D-dimer
D-dimer is a fibrin degradation product , a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis. It is so named because it contains two crosslinked D fragments of the fibrinogen protein....
", are generally normal despite the low platelet count (thrombocytopenia).
HUS occurs after 2-7% of all E. coli O157:H7 infections. Children and adolescents are commonly affected. Grossly, the kidneys may show patchy or diffuse renal cortical
Renal cortex
The renal cortex is the outer portion of the kidney between the renal capsule and the renal medulla. In the adult, it forms a continuous smooth outer zone with a number of projections that extend down between the pyramids. It contains the renal corpuscles and the renal tubules except for parts of...
necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
. Histologically
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
, the glomeruli
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
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
Mesangium
The mesangium is an inner layer of the glomerulus, within the basement membrane surrounding the glomerular capillaries. This term is often used interchangeably with mesangial cell, but in this context refers specifically to the intraglomerular mesangial cells. These cells are phagocytic and secrete...
are also found along with mesangiolysis. Interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
and are often occluded by thrombi.
In adults
Adult HUS has similar symptoms and pathology, but is an uncommon outcome of the following: HIVHIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
; antiphospholipid syndrome (associated with lupus erythematosus
Lupus erythematosus
Lupus erythematosus is a category for a collection of diseases with similar underlying problems with immunity . Symptoms of these diseases can affect many different body systems, including joints, skin, kidneys, blood cells, heart, and lungs...
and generalized hypercoagulability); postpartum renal failure; malignant hypertension
Malignant hypertension
Malignant hypertension or hypertensive emergency is severe hypertension with acute impairment of an organ system and the possibility of irreversible organ-damage...
; scleroderma
Scleroderma
Systemic sclerosis or systemic scleroderma is a systemic autoimmune disease or systemic connective tissue disease that is a subtype of scleroderma.-Skin symptoms:...
; and certain drugs, including some chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
drugs and other immunosuppressive agents (mitomycin
Mitomycin
The mitomycins are a family of aziridine-containing natural products isolated from Streptomyces caespitosus or Streptomyces lavendulae. One of these compounds, mitomycin C, finds use as a chemotherapeutic agent by virtue of its antitumour antibiotic activity. It is given intravenously to treat...
, ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, cisplatin
Cisplatin
Cisplatin, cisplatinum, or cis-diamminedichloroplatinum is a chemotherapy drug. It is used to treat various types of cancers, including sarcomas, some carcinomas , lymphomas, and germ cell tumors...
and bleomycin
Bleomycin
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
).
Atypical cases
A third category is referred to as familial HUS or atypical HUS (aHUS).It represents 5-10% of HUS cases and is largely due to mutations in the complement proteins factor H
Factor H
Factor H is a member of the regulators of complement activation family and is a complement control protein. It is a large , soluble glycoprotein that circulates in human plasma...
, membrane cofactor protein and factor I leading to uncontrolled complement system
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
activation.
Recurrent thromboses result in a high mortality rate.
Most reported HUS cases during the 2011 Escherichia coli O104:H4 outbreak were atypical cases.
Diagnosis
Clinically, HUS can be very hard to distinguish from thrombotic thrombocytopenic purpura. The laboratoryLaboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
features are almost identical, and not every case of HUS is preceded by diarrhea. HUS is characterized by the triad of hemolytic anemia
Hemolytic anemia
Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells , either in the blood vessels or elsewhere in the human body . It has numerous possible causes, ranging from relatively harmless to life-threatening...
, thrombocytopenia
Thrombocytopenia
Thrombocytopenia is a relative decrease of platelets in blood.A normal human platelet count ranges from 150,000 to 450,000 platelets per microliter of blood. These limits are determined by the 2.5th lower and upper percentile, so values outside this range do not necessarily indicate disease...
, and acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
. The only distinguishing feature is that in TTP, fever and neurological
Neurology
Neurology is a medical specialty dealing with disorders of the nervous system. Specifically, it deals with the diagnosis and treatment of all categories of disease involving the central, peripheral, and autonomic nervous systems, including their coverings, blood vessels, and all effector tissue,...
symptoms are often present; but this is not always the case.
A pericardial friction rub can also sometimes be heard on auscultation (uremic pericarditis).
The two conditions are sometimes treated as a single entity called TTP/HUS. However, some dispute this grouping, and TTP is now known to be caused by an acquired defect in the protein ADAMTS13
ADAMTS13
ADAMTS13 —also known as von Willebrand factor-cleaving protease —is a zinc-containing metalloprotease enzyme that cleaves von Willebrand factor , a large protein involved in blood clotting...
.
Treatment
Antibiotic treatment of E. coli O157:H7 colitis may stimulate further verotoxin production and thereby increase the risk of HUS.Treatment is generally supportive, with dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
as needed. Untreated HUS in adults, however, may progress to end-stage organ damage
Organ failure
Organ dysfunction is a condition where an organ does not perform its expected function. Organ failure is organ dysfunction to such a degree that normal homeostasis cannot be maintained without external clinical intervention.It is not a diagnosis...
. Platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
may actually worsen the outcome.
Since 2010, eculizumab
Eculizumab
Eculizumab is a monoclonal antibody directed against the complement protein C5. Eculizumab has been shown to be effective in treating paroxysmal nocturnal hemoglobinuria , a rare and sometimes life threatening disease of the blood, and is approved for this indication.Eculizumab is a recombinant...
has been used experimentally in the treatment of HUS, following approval from the European Medicines Agency in 2007 for the treatment of paroxysmal nocturnal hemoglobinuria.
In most children with postdiarrheal HUS, there is a good chance of spontaneous resolution, so observation in a hospital is often all that is necessary, with supportive care such as hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
where indicated. In children with neurological or other nonrenal involvement, and in adult cases, particularly when there is diagnostic uncertainty between HUS and TTP, plasmapheresis
Plasmapheresis
Plasmapheresis is the removal, treatment, and return of blood plasma from blood circulation. It is thus an extracorporeal therapy...
(plasma exchange) is the treatment of choice. This is generally performed daily until the platelet count is normal, using fresh frozen plasma
Fresh frozen plasma
The term fresh frozen plasma refers to the liquid portion of human blood that has been frozen and preserved after a blood donation and will be used for blood transfusion...
as the replacement fluid for the patient's plasma which is removed. Plasmapheresis may reverse the ongoing platelet consumption.
Prognosis
With aggressive treatment, more than 90% survive the acute phase. About 9% may develop end stage renal disease. About one-third of persons with HUS have abnormal kidney function many years later, and a few require long-term dialysisDialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
. Another 8% of persons with HUS have other lifelong complications, such as high blood pressure, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, blindness
Blindness
Blindness is the condition of lacking visual perception due to physiological or neurological factors.Various scales have been developed to describe the extent of vision loss and define blindness...
, paralysis
Paralysis
Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
, and the effects of having part of their colon
Colon (anatomy)
The colon is the last part of the digestive system in most vertebrates; it extracts water and salt from solid wastes before they are eliminated from the body, and is the site in which flora-aided fermentation of unabsorbed material occurs. Unlike the small intestine, the colon does not play a...
removed. The overall mortality rate from HUS is 5-15%. Children and the elderly have a worse prognosis.
Epidemiology
HUS has a peak incidence between six months and four years of age.HUS and the E. coli infections which caused it have been the source of much negative publicity for the Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(FDA), meat industries, and fast-food restaurants
Fast food
Fast food is the term given to food that can be prepared and served very quickly. While any meal with low preparation time can be considered to be fast food, typically the term refers to food sold in a restaurant or store with preheated or precooked ingredients, and served to the customer in a...
since the 1990s, especially in the Jack in the Box contaminations. It was also featured in the Robin Cook
Robin Cook (novelist)
Dr. Robin Cook is an American physician and novelist who writes about medicine and topics affecting public health....
novel Toxin
Toxin (novel)
Toxin is a 1998 suspense thriller written by Robin Cook. It tells the story of a doctor whose daughter is infected with E. coli and his investigation into how she contracted it and his battle to save her life and discover the source of her illness....
. In 2006, an epidemic of harmful E. coli emerged in the United States due to contaminated spinach
Spinach
Spinach is an edible flowering plant in the family of Amaranthaceae. It is native to central and southwestern Asia. It is an annual plant , which grows to a height of up to 30 cm. Spinach may survive over winter in temperate regions...
. The known cases have been reported at 183, 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.http://www.cnn.com/2009/HEALTH/06/22/cookie.dough.ecoli/index.html
At least 29 people died presumably from hemolytic-uremic syndrome in the 2011 E. coli O104:H4 outbreak in Europe.