Now, TTP manifests as TMA with neurological syndrome—neurological symptoms of headache, confusion, signs and symptoms of stroke, and other features. It is one of the causes of TMA. Falk: There used to be described what is known as a pentad, or five different features of TTP. What were those? Saha: The pentad that was described, many years ago, included fever, low platelet count—also known as thrombocytopenia, neurological symptoms, kidney injury and low hemoglobin or anemia.
This pentad was described years ago, but recent studies show that less than five percent of patients with TTP had the pentad of symptoms. TTP does not need to present with all of these features—they can just have one marker and still have TTP. There are various ways of pronouncing that acronym of a metalloproteinase. What is it? It is called metalloprotease because it requires a metal like calcium or zinc for this action. So, if somebody has a vessel injury, the body makes another protein known as ultra large von Willebrand factor, which is a clotting factor.
It helps in forming a clot at the site of injury of the blood vessel. Saha: This is normal. Once the platelet plug is formed and the blood vessel is repaired, you want the process to stop there. What this enzyme does, it controls the process. How does one as an individual, then, not have enough of this enzyme? Saha: In two ways. One is known as congenital TTP, where people have a defect in the genetic material that makes this enzyme.
So, if you have a genetic mutation, you do not make enough of this enzyme. These patients present early in life, also known as congenital TTP. What is that? Saha: HUS is hemolytic uremic syndrome. When it was initially described, they found that patients with TMA, instead of having neurological symptoms like in TTP, they have kidney failure. Patients with TMA who primarily have kidney involvement have something called hemolytic syndrome.
It can be caused mainly by two different entities. The first, and common one, is infections, and these infections are mainly from E. Falk: The most common one in the state of North Carolina, was at one point, a petting zoo at the North Carolina state fair. Petting goats that carried, on their fur, those bugs.
You can also get those microorganisms or bacteria from food. Saha: Yes, uncooked meat, including hamburgers , beef and other produces may be a source of this E. Saha: Correct. Complement pathway is one of our defense mechanisms that fights infections. A genetic defect or an antibody in one of these regulators lets this alternate complement pathway get activated uncontrollably and result in thrombotic microangiopathy. Falk: In terms of the genetic causes of these thrombotic microangiopathies, there is the absence or deficiency of an enzyme that cleaves the protein that stops you from bleeding, and another genetic cause of the same kind of thrombotic microangiopathy is a defect in the way we control infection.
So, both of these are genetic abnormalities that pertain to regulation of bleeding or regulation of infection—handling infections. Falk: What is the most common place for a patient to discover that they have thrombotic microangiopathy?
These are listed below:. A diagnosis of TTP and HUS should be considered whenever a person comes to the hospital with several of the symptoms mentioned above. Your doctor will perform a careful physical exam and then check some blood work.
Your doctor may examine the blood under a microscope to determine if there are any damaged red blood cells known as schistocytes. Positive testing in a child who has recently had bloody diarrhea will lead to a diagnosis of HUS. Positive testing in an adult makes TTP the most likely diagnosis.
The process occurs as follows:. Treatments usually last a few hours each and continue every days for about 2 weeks. For those with repeated episodes of TTP, a medication called rituximab is being tested to see if its use can prevent recurrences of the disease. In contrast, HUS usually improves on its own.
Patients will require hospitalization for fluids and monitoring while the disease is worsening. If kidney function declines too much, manual blood cleaning with dialysis may be necessary. As the causative bacterial infection resolves, toxin leaves the body and symptoms of HUS begin to improve.
These are often treated like TTP with plasma exchange, but there is currently some debate about this. In many cases the blood vessel damage in the kidneys and brain will reverse with time. HUS has a good prognosis. During the active phase of the disease kidney failure can often be severe enough to require manual blood cleaning with dialysis. Fortunately this is usually temporary.
In fact kidney function almost always returns to the normal range within a few months. Interested in a clinical trial? How does TMA affect my kidneys? Typical organ damage includes very high blood pressure malignant hypertension , kidney injury, abdominal pain, diarrhea, stroke, confusion, heart injury, and eye damage. Identifying the specific cause for TMA requires specialized blood and genetic testing to evaluate for the different causative diseases. Some of this testing can take weeks to months to return.
Since treatment must be initiated immediately, it is important to have a team of doctors experienced in the diagnosis and management of TMA. A team at Johns Hopkins has developed a research test that may be capable of diagnosing TMA due to problems in the complement system aHUS within several hours. Many patients are treated with therapeutic plasma exchange, a procedure in which plasma water and protein portion of blood is removed from the body and replaced with fresh donor plasma. This is effective therapy for TTP, and patients are usually treated with a combination of plasma exchange and immune suppression including corticosteroids.
For aHUS, patients are treated with an intravenous medication that blocks the complement system. For other diseases that cause TMA, the treatment focuses on managing the underlying disease. For example, infectious causes of TMA might be treated with antibiotics and supportive care.
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