What is Thrombotic Microangiopathy (TMA)?

Thrombotic Microangiopathy (often known simply as TMA) is a rare but serious medical disease. It is a pattern of damage that
can occur in the smallest blood vessels inside many of your bodys vital organs most commonly the kidney and
brain. "Microangiopathy" literally translates to "small blood vessel problem."
"Thrombotic" means that blood clots are involved.

How does TMA affect my kidneys?

In the normal kidney (as in the rest of the body), there are small blood vessels called capillaries. They are lined with a slippery
coating of cells known as endothelial cells (see Figure 1).

When the endothelial cells of capillaries become damaged, blood flow through the kidney slows (Figure 2).

The liquid part of the blood, called plasma, helps waste flow to the
kidney to be removed from your body through urine. There are also
solid particles in the blood, including red blood cells and
platelets. Red blood cells carry oxygen from your lungs to the rest of
your body, including the cells of your kidney. Platelets have the job of
plugging up any damaged part of the blood vessel to keep it from
leaking.

Defects in the blood vessel wall lining can produce rough patches that
are like potholes on a road they can slow traffic and cause a lot of
damage. Red blood cells can become deformed and then burst.
Platelets can activate and cause clots to form. The wreckage from all these events can close off entire blood vessels. In the end,
parts of your kidney can die from lack of blood flow, and your body can run low on red blood cells and platelets.

What does it look like (under the microscope)?

TMA causes changes in your kidney that can be seen under a microscope. The pictures below show blood vessels in the main
filter of the kidney (called the glomerulus). A healthy blood vessel appears as a circle with an open (white) center. Vessels
affected by TMA will be filled with a pinkish material, which is clot. Over time, parts of the kidney may die from lack of blood
flow.

TMA also changes how a drop of your blood looks under a microscope. Normal blood has completely round red blood cells and
plenty of tiny platelets. When you suffer from TMA your blood will have deformed red blood cells (called schistocytes) and no
platelets.

How did I get it?

There are several complex and often quite serious illnesses that
Diseases that cause TMA Abbreviation can lead to TMA these are listed in the table below. This article
Thrombotic Thrombocytopenic Purpura TTP will discuss the first two of these: Thrombotic
Hemolytic Uremic Syndrome HUS Thrombocytopenic Purpura and Hemolytic Uremic Syndrome.
Atypical TTP/HUS Atypical TTP/HUS Given their complicated names, it is best to refer to these by the
Malignant Hypertension --- abbreviations TTP and HUS.
Disseminated Intravascular Coagulation DIC
Syndrome of Hemolysis, Elevated Liver What are TTP and HUS?
HELLP
Enzymes, and Low Platelets
Scleroderma Renal Crisis SRC
 TTP usually occurs when platelets stick together too easily
(Figure 3). Platelets use a glue in the plasma called von
Willebrand Factor (vWF) to hold themselves together in the
form of a clot. The glue can be more or less sticky depending
on the size of its molecules so if the glue molecules become
too long, the platelets will form clots even when theyre not
supposed to. Usually the body keeps vWF glue cut to exactly
the right length with an enzyme called ADAMTS13. TTP
develops when a shortage of that enzyme results in unwanted
clotting in the small blood vessels of the kidney. The shortage
can be caused by one of the following:

a genetic problem that keeps you from producing

enough clipping enzyme

an overly active immune system that attacks and destroys your supply of clipping enzyme

In summary, your body becomes unable to keep vWF glue short enough to prevent abnormal clot and damage to the small blood
vessels of your body.

Figure 3: Summary of how TTP usually develops

In contrast, HUS most often occurs when your body is exposed to a certain type of toxin (Figure 4). The toxin usually comes
from a bacterial infection of the intestines. Generally this infection must be serious enough to cause bloody diarrhea. The toxin
makes its way into the blood stream and then damages endothelial cells in the kidney. This triggers platelets to clot and red blood
cells to burst as described above. For unknown reasons HUS usually occurs in children rather than adults.

Figure 4: Summary of how HUS usually

develops

There are also many less typical patterns of TTP and HUS.
Doctors have not yet determined exactly why they occur,
but they usually only happen to people who already have
another chronic medical condition. Examples of conditions
that can lead to this atypical TTP and HUS include
pregnancy, organ transplant, and diseases like HIV, lupus,
and cancer.

Who can get TTP and HUS?

TTP and HUS are quite rare. A city with a population of 1 million will average only about 11 cases in a given year. Women and
blacks are somewhat more likely to develop the diseases. For unknown reasons HUS is much more common in children, and TTP
is more common in adults.

What are the symptoms?

TTP, HUS, and the other varieties of TMA have a number of symptoms in common. These are listed below:

Symptom Reason symptom occurs

Fatigue, Dizziness, Shortness of breath
Bruises, Gum/nose bleeds, Minor cuts bleed a lot
Confusion, Sleepiness, Seizures
Decreased urine, Swollen legs, High blood pressure
Fever (more common with TTP)
Low red blood cell count
Low platelet count
Damage to blood cells in the brain
Damage to blood vessels in the kidney
How is it diagnosed?

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. The following test results
raise significant concern for TTP or HUS:

Extremely low platelet count with otherwise normal clotting factors

Mild to moderately low red blood cell count

Abnormal kidney functioned (measured with a lab test called creatinine)

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.

What is the treatment?

Figure 5: Diagram of Plasma Exchange

TTP and HUS have different treatments. To prevent death and serious organ damage
TTP requires immediate treatment with plasma exchange (PLEX) see Figure 5 for a
diagram. The process occurs as follows:

1. A large IV called a PLEX catheter is placed into one of your veins (usually in your neck or groin).

2. Your blood is then carried from that catheter through tubing to a plasma exchange machine.

3. The plasma (liquid) part of your blood is removed and then replaced with plasma from a blood donor.

4. The treated blood is returned to the catheter and then back into your body.

This process allows the abnormal glue (vWF) that causes TTP to be exchanged for normal vWF. Treatments usually last a few
hours each and continue every 1-2 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.

In many of the more atypical TTP/HUS disease patterns the optimal treatment has not yet been standardized. These are often
treated (like TTP) with plasma exchange, but there is currently some debate about this.

What are the chances that I will get better?

TTP was once fatal in 90% of individuals who developed the disease. Now that plasma exchange is available, survival can be as
high as 80%. 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