Atypical Hemolytic-Uremic Syndrome - Causes, Symptoms, Diagnosis, and Treatment

What Is an Atypical Hemolytic Uremic Syndrome?

Atypical hemolytic uremic syndrome (aHUS) is a rare disease that causes abnormal blood clots in small blood vessels, primarily in your kidneys and also in other organs. These clots prevent blood flow to your kidneys, leading to serious medical complications, including kidney failure. There is no cure, but treatment can be helpful in managing the condition.

Besides kidney failure, other complications caused by aHUS may include:

• Hemolytic anemia (red blood cells dying before their life span).

• Thrombocytopenia (low platelet count in the blood).

The atypical hemolytic uremic syndrome (aHUS) varies from "typical" hemolytic uremic syndrome, a more common condition. The typical hemolytic uremic syndrome presents with different symptoms and causes.

The aHUS can occur at any age. In children, boys and girls are equally at risk of getting it. Later in life, women tend to get it more than men because pregnancy can be a triggering factor for the disease.

What Causes Atypical Hemolytic Uremic Syndrome?

Most cases of aHUS occur because of changes or alterations in a gene called a mutation. The mutation itself is not enough for the disease to happen. The symptoms of the disease appear after certain factors that act as a trigger, such as:

• Infection.

• Pregnancy.

• Certain Medications.

• Certain chronic diseases like systemic sclerosis (hardening and tightening of the skin) or malignant hypertension (very high blood pressure suddenly and quickly).

• Cancer.

• Organ Transplant.

Doctors did not find any gene mutation in up to half of the people with aHUS. This type of aHUS is termed "idiopathic," meaning the cause is unknown. Researchers suggest that these idiopathic cases of aHUS occur may be due to gene mutations that have not been identified.

What Are the Signs and Symptoms of Atypical Hemolytic Uremic Syndrome?

The onset of aHUS ranges from before birth (prenatally) to adulthood. In young children, the disease often occurs suddenly and follows an infection, particularly an upper respiratory tract infection or gastroenteritis (intestinal infection).

Many affected people have vague feelings of irritability, fatigue, illness, and lethargy, potentially leading to hospitalization. The early stages may be challenging to diagnose, and the disease tends to be progressive. Because relapse and complications are common, aHUS must be recognized at this stage.

The primary findings of aHUS are-

• Hemolytic Anemia.

• Thrombocytopenia.

• Acute kidney failure.

Although most patients develop these three conditions, some will not.

• Hemolytic anemia is a condition with premature destruction (hemolysis) of red blood cells.

• Thrombocytopenia is a condition in which the platelet levels (blood clotting cells) decrease in the blood.

• Kidney disease can range from mild to severe. The damage to the kidneys tends to worsen with each subsequent episode. The presence of blood and protein in the urine (hematuria and proteinuria, respectively) are frequent indicators of kidney disease, especially during acute attacks. Kidney damage is progressive and can lead to end-stage renal failure, necessitating chronic dialysis or a kidney transplant.

• Hypertension (high blood pressure) is expected. It can occur due to kidney disease or lack of blood flow (ischemia) due to the formation of abnormal small blood clots (microthrombi). Hypertension can be severe and may be associated with headaches and seizures.

• Because these abnormal small blood clots can potentially form in blood vessels of other body organs, organ damage, and failure can also occur elsewhere besides the kidneys (which is the organ that is most commonly affected). The brain, digestive tract, lungs, liver, and heart can also be affected. Specific symptoms can be different based on the particular organ involved. Cardiovascular complications may include heart muscle disease (cardiomyopathy) or heart attack (myocardial infarction). Neurological complications include headaches, irritability, facial paralysis, double vision (diplopia), drowsiness, seizures, stroke, and coma. Gastrointestinal bleeding may also occur. The lungs can also get affected, and bleeding or fluid accumulation in the lungs (pulmonary edema) can occur.

How to Diagnose Atypical Hemolytic Uremic Syndrome?

The diagnosis of aHUS can be tricky if the affected individual does not have a family history of the disease. A nephrologist (kidney specialist) or hematologist (blood specialist) will most likely know about aHUS. These doctors will look for the following signs:

• Hemolytic anemia.

• Low count of platelets (blood cells that help with clotting).

• Kidney problems.

A complete blood count (CBC) is often ordered to measure the platelet count and red blood cell levels. The healthcare provider will also check for the normal functioning of the kidneys with a routine test called eGFR (estimated glomerular filtration rate). This test checks for the blood's creatinine levels, a waste product.

Because aHUS looks similar to a condition called thrombotic thrombocytopenic purpura (TTP), the doctor will also test the blood for a specific protein called ADAMTS13. If the levels of this protein are low, it indicates TTP instead of aHUS.

How Is Atypical Hemolytic Uremic Syndrome Treated?

The FDA has approved two drugs for the treatment of aHUS:

• Eculizumab.

• Ravulizumab.

Both the drugs mentioned above are monoclonal antibodies. These are artificial proteins that act like natural antibody proteins in the body. They get attached to other proteins called antigens and direct the immune system to destroy cells.

Eculizumab can increase the blood platelet and red blood cell counts. If taken early, it can also help in reversing any kidney damage.

The doctor will administer Eculizumab by injection. The drug may have some side effects, including:

• Headache.

• Back pain.

• Cold or flu-like symptoms.

• Irritated nose or throat.

• Dizziness and tiredness.

• Constipation.

• Nausea and vomiting.

• Stomach pain and diarrhea.

• Trouble sleeping.

• Muscle or joint pain.

• Muscle spasms.

• Hair loss.

The doctor can also give Ravulizumab as an injection. Common side effects of this drug include headache, cold symptoms, and high blood pressure. Digestive system problems include diarrhea, nausea, and vomiting. Eculizumab and Ravulizumab are a type of drugs called complement inhibitors.

Plasma therapy can also be used to treat the symptoms of aHUS. Plasma is the liquid portion of the blood that carries essential nutrients, proteins, and hormones throughout the body.

If the kidneys do not respond to treatment, kidney dialysis or a kidney transplant may be needed.

Conclusion:

Atypical hemolytic uremic syndrome is a rare disease in which abnormal blood clots get formed in the kidney's small blood vessels. The three main findings of this disease include low platelet count, hemolytic anemia, and kidney disease, which can progress into kidney failure. Although being a lifelong condition, early treatment can help to manage the symptoms.