Hemolytic-uremic syndrome (HUS) is a rare but serious medical condition characterized by the simultaneous occurrence of hemolytic anemia, acute kidney injury, and low platelet count.
This syndrome primarily affects the blood and blood vessels, leading to potentially life-threatening complications, particularly in young children and the elderly.
HUS presents as a medical emergency, requiring prompt diagnosis and immediate medical intervention. While it predominantly affects children, adults can also develop this condition, especially if they have certain underlying health conditions or compromised immune systems.
Epidemiology
Incidence: In the US, there are roughly 2.2 instances of hemolytic uremic syndrome for every 100,000 people. Children under the age of five have the highest incidence in the US.
HUS is relatively rare but can occur in both children and adults. It is more commonly seen in children, especially those under the age of 5. In pediatric populations, it’s one of the most common causes of acute kidney injury.
Seasonal Variation: Cases of HUS, especially those related to E. coli infections, often show a seasonal pattern, with higher incidences reported during the summer months. This pattern might be linked to increased exposure to contaminated food or water during warmer weather.
Transmission: The primary mode of transmission for HUS caused by E. coli O157:H7 is through ingestion of food that are contaminated like ground beef undercooked, unpasteurized milk or juice, contaminated vegetables, and sometimes through contact with animals or their environment.
Outbreaks: HUS outbreaks can occur, often associated with foodborne outbreaks of E. coli infections. Contaminated food supplies or water sources can lead to multiple cases in a community or across regions.
Anatomy
Pathophysiology
Typical Hemolytic-Uremic Syndrome (tHUS):
Most cases (about 90%) of HUS in children are caused by infection with Shiga toxin-producing Escherichia coli (STEC), primarily E. coli O157:H7.
The bacteria release shiga toxin when contaminated food or water is consumed, which enters the bloodstream and primarily targets the endothelial cells lining the blood vessels, especially in the kidneys and gastrointestinal tract.
Shiga toxin causes damage to the endothelial cells, leading to inflammation, activation of the clotting system, and damage to red blood cells (hemolysis), resulting in hemolytic anemia and the formation of blood clots in small blood vessels.
The blood clots occlude small blood vessels, particularly in the kidneys, leading to ischemia and damage to the kidneys’ delicate filtering units, the glomeruli. This damage results in acute kidney injury and impaired renal function.
Atypical Hemolytic-Uremic Syndrome (aHUS):
Atypical HUS is less common and is associated with abnormalities in the complement system, a part of the immune system involved in clearing pathogens and cellular debris.
In aHUS, there is dysregulation of the complement system, leading to excessive activation of the complement cascade. This dysregulation can be due to genetic mutations affecting complement regulatory proteins or acquired abnormalities in the complement system.
Excessive complement activation leads to inflammation, endothelial cell damage, platelet activation, and the accumulation of blood clots in the kidneys and other minor blood arteries throughout the body.
The resulting thrombotic microangiopathy (TMA) causes mechanical damage to RBC, which leads to hemolysis, and compromises blood flow in the kidneys, contributing to acute kidney injury.
Etiology
Certain medications: Some medications, particularly immunosuppressants and chemotherapeutic drugs, might elevate the likelihood of HUS development in people who are susceptible to it.
Other infections: Besides STEC, other infections like certain viruses and parasites may rarely trigger HUS.
Autoimmune conditions: In rare cases, autoimmune conditions affecting the blood vessels can contribute to the development of HUS.
Genetics
Prognostic Factors
The average HUS patient has a good prognosis, with a 5% total estimated mortality rate. However, with a glomerular filtration rate <80 mL/min/1.73 m2 or proteinuria, up to 25% of individuals with HUS experience long-term renal insufficiency, which may put them at risk for worsening renal insufficiency as they age.
The duration of dialysis is a major prognostic factor for continued renal failure, with long-term consequences becoming apparent after two to three weeks of dialysis use. Adults over 60, who account for most fatalities, are an exception to the low usual HUS mortality rate.
Clinical History
Age group
Hemolytic-uremic syndrome (HUS) can affect individuals of any age group, but it is more commonly seen in young children, especially those under the age of 5. But older children and adults can also experience it.
The incidence of HUS varies across different age groups but is most frequently associated with young children, often following a gastrointestinal infection caused by certain strains of Escherichia coli (E. coli), particularly O157:H7.
Physical Examination
Vital Signs: Blood pressure may be elevated, especially in severe cases. Other vital signs such as heart rate, respiratory rate, and temperature may be within normal limits unless there are complications or associated infections.
Skin: Examination of the skin might reveal pallor due to anemia, or in severe cases, evidence of bruising, petechiae (small red or purple spots caused by bleeding under the skin), or purpura (larger areas of bleeding into the skin). Jaundice may be present due to the breakdown of red blood cells.
Abdomen: Tenderness or discomfort in the abdominal region may be present. Abdominal examination may reveal signs of distension, which could indicate bloating or fluid accumulation due to kidney dysfunction.
Neurological Examination: In some cases, patients might exhibit neurological symptoms such as confusion, seizures, or altered mental status, especially in severe cases or when there’s involvement of the central nervous system due to uremia (buildup of waste products in the blood).
Age group
Associated comorbidity
Infection with E. coli O157:H7: This strain of E. coli is commonly linked to cases of HUS, especially in young children. One may ingest these bacteria through contaminated food, drink, or direct contact with diseased animals, leading to subsequent illness and potentially HUS.
Other less common causes or associations with HUS may include:
Other Infections: Besides E. coli O157:H7, other infections like certain viruses or bacteria may also trigger HUS in rare cases.
Genetic Predisposition: There are genetic factors that can increase susceptibility to developing HUS, though these instances are less frequent.
Associated activity
Acuity of presentation
Prodromal Phase: HUS often begins with a prodromal phase, usually characterized by non-specific symptoms such as fatigue, irritability, abdominal pain, vomiting, and diarrhea. This phase can last for several days before progressing to more severe symptoms.
Hemolytic Anemia: As the condition progresses, patients may develop signs of hemolytic anemia, which can include pale skin, weakness, fatigue, jaundice & dark-colored urine due to the presence of hemoglobin breakdown products.
Acute Kidney Injury (AKI): One of the characteristic features of HUS is the development of acute kidney injury. This can manifest as decreased urine output, swelling (edema) in the legs, ankles, or other parts of the body, high blood pressure, and signs of uremia such as nausea, vomiting, and confusion because of the blood’s accumulation of waste materials.
Low Platelet Count: HUS can also lead to thrombocytopenia, a low platelet count, which may result in increased bleeding tendencies.
Neurological Symptoms: In severe cases or if the central nervous system is affected, patients may experience seizures, altered mental status, or even coma. These neurological symptoms can occur due to complications related to kidney failure or as a direct result of the underlying disease process affecting the brain.
Multi-organ Involvement: HUS can affect multiple organ systems beyond the kidneys and blood, potentially leading to complications in the heart, pancreas, and central nervous system.
Differential Diagnoses
Thrombotic Thrombocytopenic Purpura (TTP): Often confused with HUS due to similar symptoms. TTP involves widespread microscopic blood clots in small blood vessels, leading to thrombocytopenia and microangiopathic hemolytic anemia.
Disseminated Intravascular Coagulation (DIC): A condition causing abnormal blood clotting throughout the body, resulting in both bleeding and clotting, which can lead to thrombocytopenia and hemolysis.
Acute Kidney Injury (AKI) due to other causes: Conditions such as acute tubular necrosis, glomerulonephritis, or other forms of renal injury can present similarly to HUS.
Systemic Infections: Certain bacterial infections, particularly those caused by Escherichia coli (E. coli), Shigella, Salmonella, or other pathogens, can cause a similar clinical presentation, leading to hemolytic-uremic syndrome.
Autoimmune Hemolytic Anemia: Conditions where the immune system mistakenly attacks red blood cells, leading to their destruction and potentially causing similar symptoms of anemia and low platelet count.
Medication-Induced Hemolytic Anemia: Some medications or toxins can induce hemolysis, leading to anemia and potentially kidney damage.
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Hospitalization and Supportive Care:
Patients with HUS often require hospitalization, especially if they have severe symptoms such as kidney failure or complications like seizures.
Supportive care involves close monitoring of vital signs, fluid balance, and electrolyte levels.
Intravenous fluids may be administered to maintain hydration and support kidney function.
Management of Complications:
Kidney Failure: Management of kidney failure may involve dialysis or plasmapheresis (a procedure to remove harmful substances from the blood).
Hypertension: Controlling blood pressure is crucial to prevent further damage to the kidneys. Medications like ACE inhibitors & ARBs may be prescribed.
Anemia and Low Platelet Count: Blood transfusions might be necessary to manage anemia and low platelet count.
Avoidance of Nephrotoxic Medications: Medications that can potentially harm the kidneys, such as certain antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs), should be avoided.
Treatment of Underlying Cause:
HUS is often caused by infection with certain strains of Escherichia coli (E. coli), particularly E. coli O157:H7. For E. Coli infections linked to HUS, antibiotics are typically not advised since they may raise the risk of consequences.
If the cause is related to other conditions or factors, such as certain medications or genetic factors, addressing these underlying causes is crucial.
Nutritional Support:
A balanced diet and nutritional support may be necessary to maintain overall health, especially if kidney function is compromised.
Follow-up Care:
Long-term follow-up care is essential for patients who have had HUS, in especially to track renal function and handle any possible side effects.
Preventive Measures:
Emphasizing proper hygiene, safe food handling, and avoiding contaminated food or water sources can help prevent certain types of infections that may lead to HUS.
Food Safety: HUS is often associated with bacterial infections, particularly from E. coli O157:H7. Ensuring proper food safety measures such as thoroughly cooking meats, washing fruits and vegetables, and preventing cross-contamination can reduce the risk of infection.
Hygiene Practices: Emphasize good hygiene, including regular handwashing with soap and water, especially after using the restroom, changing diapers, and before handling food. This helps in reducing the transmission of infectious agents that can lead to HUS.
Safe Water: Ensure access to clean and safe drinking water. Avoid drinking untreated water or water from potentially contaminated sources.
Proper Medical Care: Promptly treat any gastrointestinal infections, as some cases of HUS can develop after an infection. Seek medical attention if you or your child experiences persistent diarrhea or any concerning symptoms.
Childcare Practices: In childcare settings, ensure proper hygiene practices, including frequent handwashing for both children and caregivers. Promptly dispose of diapers and maintain a clean environment to prevent the spread of infections.
Vaccinations: Stay up to date with vaccinations, as some infections, such as those caused by certain strains of E. coli, can lead to HUS. Vaccination against specific bacterial infections can reduce the risk of developing HUS.
Educational Awareness: Educate yourself and others, especially parents and caregivers of young children, about the symptoms and risks associated with HUS. Awareness helps in prompt recognition and seeking medical attention if necessary.
Effectiveness of monoclonal antibody for treating aHUS
The FDA approved eculizumab in 2011 for the treatment of atypical HUS. A humanised monoclonal antibody directed against C5, eculizumab prevents the activation of complement’s terminal components.
Eculizumab’s safety and efficacy in treating atypical HUS were demonstrated in two single-arm trials including 37 adults and adolescents, as well as one retrospective research with 11 adult and 19 paediatric patients.
Treatment with eculizumab improved kidney function in those studies, and in numerous individuals that had not responded to plasma therapy, dialysis was no longer necessary. Additionally, platelet counts, and other blood indicators improved in patients receiving eculizumab treatment.
For the treatment of aHUS in adult and paediatric patients one month of age and more, ravelizumab was approved by the FDA in 2019 october.
A monoclonal blocking antibody for complement protein C5 is called ravulizumab; by suppressing cleavage to C5a and C5b, it prevents the formation of the final complement complex C5b-9, which in turn stops RBC hemolysis.
When used in conjunction with aHUS, it prevents complement-mediated thrombotic microangiopathy and terminal complement-mediated intravascular hemolysis in individuals with paroxysmal nocturnal hemoglobinuria.
Kidney Transplant: In extremely severe cases of kidney failure due to HUS, a kidney transplant might be considered as a treatment option. This involves a surgical procedure where a healthy kidney from a donor is implanted to replace the failed kidney.
Prompt recognition and diagnosis of HUS based on clinical presentation, laboratory tests (such as blood tests, urine tests, and stool cultures), and medical history.
Immediate medical intervention to stabilize the patient, especially if there are signs of severe kidney involvement, electrolyte imbalances, or other complications.
Supportive Care:
Fluid and electrolyte management: Intravenous fluids to maintain hydration and electrolyte balance. Monitoring and correction of electrolyte abnormalities, especially potassium and sodium levels, are crucial.
Nutrition support: Ensuring adequate nutrition either through oral intake or, if necessary, through alternative methods such as tube feeding or intravenous nutrition.
Treatment of Complications:
Renal support: Dialysis may be necessary in severe cases to manage kidney failure and remove waste products from the blood.
Management of hypertension (high blood pressure): Medications may be prescribed to control blood pressure, which can help protect the kidneys and other organs.
Red blood cell transfusions or other interventions to address anemia if present.
Monitoring and Management of Long-Term Effects:
Ongoing monitoring of kidney function and other affected organs.
Follow-up care to assess recovery, manage any residual complications, and prevent recurrence.
Preventive Measures:
Infection control: Preventing and promptly treating infections, especially those caused by certain strains of E. coli that can lead to HUS.
Public health measures: Educating the public about food safety, proper hygiene, and measures to prevent the transmission of infectious agents that can cause HUS.
Rehabilitation and Support:
Rehabilitation services may be needed for patients who experienced severe complications or prolonged hospital stays to regain strength, mobility, and functionality.
Hemolytic-uremic syndrome (HUS) is a rare but serious medical condition characterized by the simultaneous occurrence of hemolytic anemia, acute kidney injury, and low platelet count.
This syndrome primarily affects the blood and blood vessels, leading to potentially life-threatening complications, particularly in young children and the elderly.
HUS presents as a medical emergency, requiring prompt diagnosis and immediate medical intervention. While it predominantly affects children, adults can also develop this condition, especially if they have certain underlying health conditions or compromised immune systems.
Incidence: In the US, there are roughly 2.2 instances of hemolytic uremic syndrome for every 100,000 people. Children under the age of five have the highest incidence in the US.
HUS is relatively rare but can occur in both children and adults. It is more commonly seen in children, especially those under the age of 5. In pediatric populations, it’s one of the most common causes of acute kidney injury.
Seasonal Variation: Cases of HUS, especially those related to E. coli infections, often show a seasonal pattern, with higher incidences reported during the summer months. This pattern might be linked to increased exposure to contaminated food or water during warmer weather.
Transmission: The primary mode of transmission for HUS caused by E. coli O157:H7 is through ingestion of food that are contaminated like ground beef undercooked, unpasteurized milk or juice, contaminated vegetables, and sometimes through contact with animals or their environment.
Outbreaks: HUS outbreaks can occur, often associated with foodborne outbreaks of E. coli infections. Contaminated food supplies or water sources can lead to multiple cases in a community or across regions.
Typical Hemolytic-Uremic Syndrome (tHUS):
Most cases (about 90%) of HUS in children are caused by infection with Shiga toxin-producing Escherichia coli (STEC), primarily E. coli O157:H7.
The bacteria release shiga toxin when contaminated food or water is consumed, which enters the bloodstream and primarily targets the endothelial cells lining the blood vessels, especially in the kidneys and gastrointestinal tract.
Shiga toxin causes damage to the endothelial cells, leading to inflammation, activation of the clotting system, and damage to red blood cells (hemolysis), resulting in hemolytic anemia and the formation of blood clots in small blood vessels.
The blood clots occlude small blood vessels, particularly in the kidneys, leading to ischemia and damage to the kidneys’ delicate filtering units, the glomeruli. This damage results in acute kidney injury and impaired renal function.
Atypical Hemolytic-Uremic Syndrome (aHUS):
Atypical HUS is less common and is associated with abnormalities in the complement system, a part of the immune system involved in clearing pathogens and cellular debris.
In aHUS, there is dysregulation of the complement system, leading to excessive activation of the complement cascade. This dysregulation can be due to genetic mutations affecting complement regulatory proteins or acquired abnormalities in the complement system.
Excessive complement activation leads to inflammation, endothelial cell damage, platelet activation, and the accumulation of blood clots in the kidneys and other minor blood arteries throughout the body.
The resulting thrombotic microangiopathy (TMA) causes mechanical damage to RBC, which leads to hemolysis, and compromises blood flow in the kidneys, contributing to acute kidney injury.
Certain medications: Some medications, particularly immunosuppressants and chemotherapeutic drugs, might elevate the likelihood of HUS development in people who are susceptible to it.
Other infections: Besides STEC, other infections like certain viruses and parasites may rarely trigger HUS.
Autoimmune conditions: In rare cases, autoimmune conditions affecting the blood vessels can contribute to the development of HUS.
The average HUS patient has a good prognosis, with a 5% total estimated mortality rate. However, with a glomerular filtration rate <80 mL/min/1.73 m2 or proteinuria, up to 25% of individuals with HUS experience long-term renal insufficiency, which may put them at risk for worsening renal insufficiency as they age.
The duration of dialysis is a major prognostic factor for continued renal failure, with long-term consequences becoming apparent after two to three weeks of dialysis use. Adults over 60, who account for most fatalities, are an exception to the low usual HUS mortality rate.
Age group
Hemolytic-uremic syndrome (HUS) can affect individuals of any age group, but it is more commonly seen in young children, especially those under the age of 5. But older children and adults can also experience it.
The incidence of HUS varies across different age groups but is most frequently associated with young children, often following a gastrointestinal infection caused by certain strains of Escherichia coli (E. coli), particularly O157:H7.
Vital Signs: Blood pressure may be elevated, especially in severe cases. Other vital signs such as heart rate, respiratory rate, and temperature may be within normal limits unless there are complications or associated infections.
Skin: Examination of the skin might reveal pallor due to anemia, or in severe cases, evidence of bruising, petechiae (small red or purple spots caused by bleeding under the skin), or purpura (larger areas of bleeding into the skin). Jaundice may be present due to the breakdown of red blood cells.
Abdomen: Tenderness or discomfort in the abdominal region may be present. Abdominal examination may reveal signs of distension, which could indicate bloating or fluid accumulation due to kidney dysfunction.
Neurological Examination: In some cases, patients might exhibit neurological symptoms such as confusion, seizures, or altered mental status, especially in severe cases or when there’s involvement of the central nervous system due to uremia (buildup of waste products in the blood).
Infection with E. coli O157:H7: This strain of E. coli is commonly linked to cases of HUS, especially in young children. One may ingest these bacteria through contaminated food, drink, or direct contact with diseased animals, leading to subsequent illness and potentially HUS.
Other less common causes or associations with HUS may include:
Other Infections: Besides E. coli O157:H7, other infections like certain viruses or bacteria may also trigger HUS in rare cases.
Genetic Predisposition: There are genetic factors that can increase susceptibility to developing HUS, though these instances are less frequent.
Prodromal Phase: HUS often begins with a prodromal phase, usually characterized by non-specific symptoms such as fatigue, irritability, abdominal pain, vomiting, and diarrhea. This phase can last for several days before progressing to more severe symptoms.
Hemolytic Anemia: As the condition progresses, patients may develop signs of hemolytic anemia, which can include pale skin, weakness, fatigue, jaundice & dark-colored urine due to the presence of hemoglobin breakdown products.
Acute Kidney Injury (AKI): One of the characteristic features of HUS is the development of acute kidney injury. This can manifest as decreased urine output, swelling (edema) in the legs, ankles, or other parts of the body, high blood pressure, and signs of uremia such as nausea, vomiting, and confusion because of the blood’s accumulation of waste materials.
Low Platelet Count: HUS can also lead to thrombocytopenia, a low platelet count, which may result in increased bleeding tendencies.
Neurological Symptoms: In severe cases or if the central nervous system is affected, patients may experience seizures, altered mental status, or even coma. These neurological symptoms can occur due to complications related to kidney failure or as a direct result of the underlying disease process affecting the brain.
Multi-organ Involvement: HUS can affect multiple organ systems beyond the kidneys and blood, potentially leading to complications in the heart, pancreas, and central nervous system.
Thrombotic Thrombocytopenic Purpura (TTP): Often confused with HUS due to similar symptoms. TTP involves widespread microscopic blood clots in small blood vessels, leading to thrombocytopenia and microangiopathic hemolytic anemia.
Disseminated Intravascular Coagulation (DIC): A condition causing abnormal blood clotting throughout the body, resulting in both bleeding and clotting, which can lead to thrombocytopenia and hemolysis.
Acute Kidney Injury (AKI) due to other causes: Conditions such as acute tubular necrosis, glomerulonephritis, or other forms of renal injury can present similarly to HUS.
Systemic Infections: Certain bacterial infections, particularly those caused by Escherichia coli (E. coli), Shigella, Salmonella, or other pathogens, can cause a similar clinical presentation, leading to hemolytic-uremic syndrome.
Autoimmune Hemolytic Anemia: Conditions where the immune system mistakenly attacks red blood cells, leading to their destruction and potentially causing similar symptoms of anemia and low platelet count.
Medication-Induced Hemolytic Anemia: Some medications or toxins can induce hemolysis, leading to anemia and potentially kidney damage.
Hospitalization and Supportive Care:
Patients with HUS often require hospitalization, especially if they have severe symptoms such as kidney failure or complications like seizures.
Supportive care involves close monitoring of vital signs, fluid balance, and electrolyte levels.
Intravenous fluids may be administered to maintain hydration and support kidney function.
Management of Complications:
Kidney Failure: Management of kidney failure may involve dialysis or plasmapheresis (a procedure to remove harmful substances from the blood).
Hypertension: Controlling blood pressure is crucial to prevent further damage to the kidneys. Medications like ACE inhibitors & ARBs may be prescribed.
Anemia and Low Platelet Count: Blood transfusions might be necessary to manage anemia and low platelet count.
Avoidance of Nephrotoxic Medications: Medications that can potentially harm the kidneys, such as certain antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs), should be avoided.
Treatment of Underlying Cause:
HUS is often caused by infection with certain strains of Escherichia coli (E. coli), particularly E. coli O157:H7. For E. Coli infections linked to HUS, antibiotics are typically not advised since they may raise the risk of consequences.
If the cause is related to other conditions or factors, such as certain medications or genetic factors, addressing these underlying causes is crucial.
Nutritional Support:
A balanced diet and nutritional support may be necessary to maintain overall health, especially if kidney function is compromised.
Follow-up Care:
Long-term follow-up care is essential for patients who have had HUS, in especially to track renal function and handle any possible side effects.
Preventive Measures:
Emphasizing proper hygiene, safe food handling, and avoiding contaminated food or water sources can help prevent certain types of infections that may lead to HUS.
Hematology
Food Safety: HUS is often associated with bacterial infections, particularly from E. coli O157:H7. Ensuring proper food safety measures such as thoroughly cooking meats, washing fruits and vegetables, and preventing cross-contamination can reduce the risk of infection.
Hygiene Practices: Emphasize good hygiene, including regular handwashing with soap and water, especially after using the restroom, changing diapers, and before handling food. This helps in reducing the transmission of infectious agents that can lead to HUS.
Safe Water: Ensure access to clean and safe drinking water. Avoid drinking untreated water or water from potentially contaminated sources.
Proper Medical Care: Promptly treat any gastrointestinal infections, as some cases of HUS can develop after an infection. Seek medical attention if you or your child experiences persistent diarrhea or any concerning symptoms.
Childcare Practices: In childcare settings, ensure proper hygiene practices, including frequent handwashing for both children and caregivers. Promptly dispose of diapers and maintain a clean environment to prevent the spread of infections.
Vaccinations: Stay up to date with vaccinations, as some infections, such as those caused by certain strains of E. coli, can lead to HUS. Vaccination against specific bacterial infections can reduce the risk of developing HUS.
Educational Awareness: Educate yourself and others, especially parents and caregivers of young children, about the symptoms and risks associated with HUS. Awareness helps in prompt recognition and seeking medical attention if necessary.
The FDA approved eculizumab in 2011 for the treatment of atypical HUS. A humanised monoclonal antibody directed against C5, eculizumab prevents the activation of complement’s terminal components.
Eculizumab’s safety and efficacy in treating atypical HUS were demonstrated in two single-arm trials including 37 adults and adolescents, as well as one retrospective research with 11 adult and 19 paediatric patients.
Treatment with eculizumab improved kidney function in those studies, and in numerous individuals that had not responded to plasma therapy, dialysis was no longer necessary. Additionally, platelet counts, and other blood indicators improved in patients receiving eculizumab treatment.
For the treatment of aHUS in adult and paediatric patients one month of age and more, ravelizumab was approved by the FDA in 2019 october.
A monoclonal blocking antibody for complement protein C5 is called ravulizumab; by suppressing cleavage to C5a and C5b, it prevents the formation of the final complement complex C5b-9, which in turn stops RBC hemolysis.
When used in conjunction with aHUS, it prevents complement-mediated thrombotic microangiopathy and terminal complement-mediated intravascular hemolysis in individuals with paroxysmal nocturnal hemoglobinuria.
Hematology
Kidney Transplant: In extremely severe cases of kidney failure due to HUS, a kidney transplant might be considered as a treatment option. This involves a surgical procedure where a healthy kidney from a donor is implanted to replace the failed kidney.
Hematology
Acute Phase Assessment and Diagnosis:
Prompt recognition and diagnosis of HUS based on clinical presentation, laboratory tests (such as blood tests, urine tests, and stool cultures), and medical history.
Immediate medical intervention to stabilize the patient, especially if there are signs of severe kidney involvement, electrolyte imbalances, or other complications.
Supportive Care:
Fluid and electrolyte management: Intravenous fluids to maintain hydration and electrolyte balance. Monitoring and correction of electrolyte abnormalities, especially potassium and sodium levels, are crucial.
Nutrition support: Ensuring adequate nutrition either through oral intake or, if necessary, through alternative methods such as tube feeding or intravenous nutrition.
Treatment of Complications:
Renal support: Dialysis may be necessary in severe cases to manage kidney failure and remove waste products from the blood.
Management of hypertension (high blood pressure): Medications may be prescribed to control blood pressure, which can help protect the kidneys and other organs.
Red blood cell transfusions or other interventions to address anemia if present.
Monitoring and Management of Long-Term Effects:
Ongoing monitoring of kidney function and other affected organs.
Follow-up care to assess recovery, manage any residual complications, and prevent recurrence.
Preventive Measures:
Infection control: Preventing and promptly treating infections, especially those caused by certain strains of E. coli that can lead to HUS.
Public health measures: Educating the public about food safety, proper hygiene, and measures to prevent the transmission of infectious agents that can cause HUS.
Rehabilitation and Support:
Rehabilitation services may be needed for patients who experienced severe complications or prolonged hospital stays to regain strength, mobility, and functionality.
Hemolytic-uremic syndrome (HUS) is a rare but serious medical condition characterized by the simultaneous occurrence of hemolytic anemia, acute kidney injury, and low platelet count.
This syndrome primarily affects the blood and blood vessels, leading to potentially life-threatening complications, particularly in young children and the elderly.
HUS presents as a medical emergency, requiring prompt diagnosis and immediate medical intervention. While it predominantly affects children, adults can also develop this condition, especially if they have certain underlying health conditions or compromised immune systems.
Incidence: In the US, there are roughly 2.2 instances of hemolytic uremic syndrome for every 100,000 people. Children under the age of five have the highest incidence in the US.
HUS is relatively rare but can occur in both children and adults. It is more commonly seen in children, especially those under the age of 5. In pediatric populations, it’s one of the most common causes of acute kidney injury.
Seasonal Variation: Cases of HUS, especially those related to E. coli infections, often show a seasonal pattern, with higher incidences reported during the summer months. This pattern might be linked to increased exposure to contaminated food or water during warmer weather.
Transmission: The primary mode of transmission for HUS caused by E. coli O157:H7 is through ingestion of food that are contaminated like ground beef undercooked, unpasteurized milk or juice, contaminated vegetables, and sometimes through contact with animals or their environment.
Outbreaks: HUS outbreaks can occur, often associated with foodborne outbreaks of E. coli infections. Contaminated food supplies or water sources can lead to multiple cases in a community or across regions.
Typical Hemolytic-Uremic Syndrome (tHUS):
Most cases (about 90%) of HUS in children are caused by infection with Shiga toxin-producing Escherichia coli (STEC), primarily E. coli O157:H7.
The bacteria release shiga toxin when contaminated food or water is consumed, which enters the bloodstream and primarily targets the endothelial cells lining the blood vessels, especially in the kidneys and gastrointestinal tract.
Shiga toxin causes damage to the endothelial cells, leading to inflammation, activation of the clotting system, and damage to red blood cells (hemolysis), resulting in hemolytic anemia and the formation of blood clots in small blood vessels.
The blood clots occlude small blood vessels, particularly in the kidneys, leading to ischemia and damage to the kidneys’ delicate filtering units, the glomeruli. This damage results in acute kidney injury and impaired renal function.
Atypical Hemolytic-Uremic Syndrome (aHUS):
Atypical HUS is less common and is associated with abnormalities in the complement system, a part of the immune system involved in clearing pathogens and cellular debris.
In aHUS, there is dysregulation of the complement system, leading to excessive activation of the complement cascade. This dysregulation can be due to genetic mutations affecting complement regulatory proteins or acquired abnormalities in the complement system.
Excessive complement activation leads to inflammation, endothelial cell damage, platelet activation, and the accumulation of blood clots in the kidneys and other minor blood arteries throughout the body.
The resulting thrombotic microangiopathy (TMA) causes mechanical damage to RBC, which leads to hemolysis, and compromises blood flow in the kidneys, contributing to acute kidney injury.
Certain medications: Some medications, particularly immunosuppressants and chemotherapeutic drugs, might elevate the likelihood of HUS development in people who are susceptible to it.
Other infections: Besides STEC, other infections like certain viruses and parasites may rarely trigger HUS.
Autoimmune conditions: In rare cases, autoimmune conditions affecting the blood vessels can contribute to the development of HUS.
The average HUS patient has a good prognosis, with a 5% total estimated mortality rate. However, with a glomerular filtration rate <80 mL/min/1.73 m2 or proteinuria, up to 25% of individuals with HUS experience long-term renal insufficiency, which may put them at risk for worsening renal insufficiency as they age.
The duration of dialysis is a major prognostic factor for continued renal failure, with long-term consequences becoming apparent after two to three weeks of dialysis use. Adults over 60, who account for most fatalities, are an exception to the low usual HUS mortality rate.
Age group
Hemolytic-uremic syndrome (HUS) can affect individuals of any age group, but it is more commonly seen in young children, especially those under the age of 5. But older children and adults can also experience it.
The incidence of HUS varies across different age groups but is most frequently associated with young children, often following a gastrointestinal infection caused by certain strains of Escherichia coli (E. coli), particularly O157:H7.
Vital Signs: Blood pressure may be elevated, especially in severe cases. Other vital signs such as heart rate, respiratory rate, and temperature may be within normal limits unless there are complications or associated infections.
Skin: Examination of the skin might reveal pallor due to anemia, or in severe cases, evidence of bruising, petechiae (small red or purple spots caused by bleeding under the skin), or purpura (larger areas of bleeding into the skin). Jaundice may be present due to the breakdown of red blood cells.
Abdomen: Tenderness or discomfort in the abdominal region may be present. Abdominal examination may reveal signs of distension, which could indicate bloating or fluid accumulation due to kidney dysfunction.
Neurological Examination: In some cases, patients might exhibit neurological symptoms such as confusion, seizures, or altered mental status, especially in severe cases or when there’s involvement of the central nervous system due to uremia (buildup of waste products in the blood).
Infection with E. coli O157:H7: This strain of E. coli is commonly linked to cases of HUS, especially in young children. One may ingest these bacteria through contaminated food, drink, or direct contact with diseased animals, leading to subsequent illness and potentially HUS.
Other less common causes or associations with HUS may include:
Other Infections: Besides E. coli O157:H7, other infections like certain viruses or bacteria may also trigger HUS in rare cases.
Genetic Predisposition: There are genetic factors that can increase susceptibility to developing HUS, though these instances are less frequent.
Prodromal Phase: HUS often begins with a prodromal phase, usually characterized by non-specific symptoms such as fatigue, irritability, abdominal pain, vomiting, and diarrhea. This phase can last for several days before progressing to more severe symptoms.
Hemolytic Anemia: As the condition progresses, patients may develop signs of hemolytic anemia, which can include pale skin, weakness, fatigue, jaundice & dark-colored urine due to the presence of hemoglobin breakdown products.
Acute Kidney Injury (AKI): One of the characteristic features of HUS is the development of acute kidney injury. This can manifest as decreased urine output, swelling (edema) in the legs, ankles, or other parts of the body, high blood pressure, and signs of uremia such as nausea, vomiting, and confusion because of the blood’s accumulation of waste materials.
Low Platelet Count: HUS can also lead to thrombocytopenia, a low platelet count, which may result in increased bleeding tendencies.
Neurological Symptoms: In severe cases or if the central nervous system is affected, patients may experience seizures, altered mental status, or even coma. These neurological symptoms can occur due to complications related to kidney failure or as a direct result of the underlying disease process affecting the brain.
Multi-organ Involvement: HUS can affect multiple organ systems beyond the kidneys and blood, potentially leading to complications in the heart, pancreas, and central nervous system.
Thrombotic Thrombocytopenic Purpura (TTP): Often confused with HUS due to similar symptoms. TTP involves widespread microscopic blood clots in small blood vessels, leading to thrombocytopenia and microangiopathic hemolytic anemia.
Disseminated Intravascular Coagulation (DIC): A condition causing abnormal blood clotting throughout the body, resulting in both bleeding and clotting, which can lead to thrombocytopenia and hemolysis.
Acute Kidney Injury (AKI) due to other causes: Conditions such as acute tubular necrosis, glomerulonephritis, or other forms of renal injury can present similarly to HUS.
Systemic Infections: Certain bacterial infections, particularly those caused by Escherichia coli (E. coli), Shigella, Salmonella, or other pathogens, can cause a similar clinical presentation, leading to hemolytic-uremic syndrome.
Autoimmune Hemolytic Anemia: Conditions where the immune system mistakenly attacks red blood cells, leading to their destruction and potentially causing similar symptoms of anemia and low platelet count.
Medication-Induced Hemolytic Anemia: Some medications or toxins can induce hemolysis, leading to anemia and potentially kidney damage.
Hospitalization and Supportive Care:
Patients with HUS often require hospitalization, especially if they have severe symptoms such as kidney failure or complications like seizures.
Supportive care involves close monitoring of vital signs, fluid balance, and electrolyte levels.
Intravenous fluids may be administered to maintain hydration and support kidney function.
Management of Complications:
Kidney Failure: Management of kidney failure may involve dialysis or plasmapheresis (a procedure to remove harmful substances from the blood).
Hypertension: Controlling blood pressure is crucial to prevent further damage to the kidneys. Medications like ACE inhibitors & ARBs may be prescribed.
Anemia and Low Platelet Count: Blood transfusions might be necessary to manage anemia and low platelet count.
Avoidance of Nephrotoxic Medications: Medications that can potentially harm the kidneys, such as certain antibiotics or nonsteroidal anti-inflammatory drugs (NSAIDs), should be avoided.
Treatment of Underlying Cause:
HUS is often caused by infection with certain strains of Escherichia coli (E. coli), particularly E. coli O157:H7. For E. Coli infections linked to HUS, antibiotics are typically not advised since they may raise the risk of consequences.
If the cause is related to other conditions or factors, such as certain medications or genetic factors, addressing these underlying causes is crucial.
Nutritional Support:
A balanced diet and nutritional support may be necessary to maintain overall health, especially if kidney function is compromised.
Follow-up Care:
Long-term follow-up care is essential for patients who have had HUS, in especially to track renal function and handle any possible side effects.
Preventive Measures:
Emphasizing proper hygiene, safe food handling, and avoiding contaminated food or water sources can help prevent certain types of infections that may lead to HUS.
Hematology
Food Safety: HUS is often associated with bacterial infections, particularly from E. coli O157:H7. Ensuring proper food safety measures such as thoroughly cooking meats, washing fruits and vegetables, and preventing cross-contamination can reduce the risk of infection.
Hygiene Practices: Emphasize good hygiene, including regular handwashing with soap and water, especially after using the restroom, changing diapers, and before handling food. This helps in reducing the transmission of infectious agents that can lead to HUS.
Safe Water: Ensure access to clean and safe drinking water. Avoid drinking untreated water or water from potentially contaminated sources.
Proper Medical Care: Promptly treat any gastrointestinal infections, as some cases of HUS can develop after an infection. Seek medical attention if you or your child experiences persistent diarrhea or any concerning symptoms.
Childcare Practices: In childcare settings, ensure proper hygiene practices, including frequent handwashing for both children and caregivers. Promptly dispose of diapers and maintain a clean environment to prevent the spread of infections.
Vaccinations: Stay up to date with vaccinations, as some infections, such as those caused by certain strains of E. coli, can lead to HUS. Vaccination against specific bacterial infections can reduce the risk of developing HUS.
Educational Awareness: Educate yourself and others, especially parents and caregivers of young children, about the symptoms and risks associated with HUS. Awareness helps in prompt recognition and seeking medical attention if necessary.
The FDA approved eculizumab in 2011 for the treatment of atypical HUS. A humanised monoclonal antibody directed against C5, eculizumab prevents the activation of complement’s terminal components.
Eculizumab’s safety and efficacy in treating atypical HUS were demonstrated in two single-arm trials including 37 adults and adolescents, as well as one retrospective research with 11 adult and 19 paediatric patients.
Treatment with eculizumab improved kidney function in those studies, and in numerous individuals that had not responded to plasma therapy, dialysis was no longer necessary. Additionally, platelet counts, and other blood indicators improved in patients receiving eculizumab treatment.
For the treatment of aHUS in adult and paediatric patients one month of age and more, ravelizumab was approved by the FDA in 2019 october.
A monoclonal blocking antibody for complement protein C5 is called ravulizumab; by suppressing cleavage to C5a and C5b, it prevents the formation of the final complement complex C5b-9, which in turn stops RBC hemolysis.
When used in conjunction with aHUS, it prevents complement-mediated thrombotic microangiopathy and terminal complement-mediated intravascular hemolysis in individuals with paroxysmal nocturnal hemoglobinuria.
Hematology
Kidney Transplant: In extremely severe cases of kidney failure due to HUS, a kidney transplant might be considered as a treatment option. This involves a surgical procedure where a healthy kidney from a donor is implanted to replace the failed kidney.
Hematology
Acute Phase Assessment and Diagnosis:
Prompt recognition and diagnosis of HUS based on clinical presentation, laboratory tests (such as blood tests, urine tests, and stool cultures), and medical history.
Immediate medical intervention to stabilize the patient, especially if there are signs of severe kidney involvement, electrolyte imbalances, or other complications.
Supportive Care:
Fluid and electrolyte management: Intravenous fluids to maintain hydration and electrolyte balance. Monitoring and correction of electrolyte abnormalities, especially potassium and sodium levels, are crucial.
Nutrition support: Ensuring adequate nutrition either through oral intake or, if necessary, through alternative methods such as tube feeding or intravenous nutrition.
Treatment of Complications:
Renal support: Dialysis may be necessary in severe cases to manage kidney failure and remove waste products from the blood.
Management of hypertension (high blood pressure): Medications may be prescribed to control blood pressure, which can help protect the kidneys and other organs.
Red blood cell transfusions or other interventions to address anemia if present.
Monitoring and Management of Long-Term Effects:
Ongoing monitoring of kidney function and other affected organs.
Follow-up care to assess recovery, manage any residual complications, and prevent recurrence.
Preventive Measures:
Infection control: Preventing and promptly treating infections, especially those caused by certain strains of E. coli that can lead to HUS.
Public health measures: Educating the public about food safety, proper hygiene, and measures to prevent the transmission of infectious agents that can cause HUS.
Rehabilitation and Support:
Rehabilitation services may be needed for patients who experienced severe complications or prolonged hospital stays to regain strength, mobility, and functionality.
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