What Is Thrombotic Thrombocytopenic Purpura?
Thrombotic thrombocytopenic purpura (TTP) is a rare
blood condition. It causes blood clots to form in small blood vessels
throughout the body. These blood clots can cause serious problems if they block
blood vessels and limit blood flow to the brain, kidneys, or heart.
Blood clots form when blood cells called platelets
(PLATE-lets) clump together. Platelets are made in your bone marrow along with
other kinds of blood cells. They stick together to seal small cuts or breaks
and stop bleeding.
In TTP, when blood clots form, there are fewer
platelets in the blood. This can cause bleeding into the skin (purpura),
prolonged bleeding from cuts, and internal bleeding. It also causes small blood
clots to form suddenly throughout the body, including in the brain and
kidneys.
Thrombotic (throm-BOT-ik) refers to the blood clots
that form. Thrombocytopenic (throm-bo-cy-toe-PEE-nick) means theres a
lower than normal number of platelets in the blood. Purpura (PURR-purr-ah) are
purple bruises caused by bleeding into the skin.
Purpura
The photograph show purpura
(bleeding) in the skin. Bleeding under the skin causes the purple, brown, and
red color of the purpura.
TTP also can cause red blood cells to break apart
faster than the body can replace them. This leads to
hemolytic
anemia (HEE-moh-lit-ick uh-NEE-me-uh)a rare form of
anemia.
Anemia is a condition in which a persons blood doesnt have enough
red blood cells.
A lack of activity in the ADAMTS13 enzyme (a type of
protein in the blood) causes TTP. The ADAMTS13 gene controls the enzyme, which
is involved in blood clotting. The enzyme breaks up a large protein called von
Willebrand factor that clumps together with platelets to form blood clots.
Types of Thrombotic Thrombocytopenic Purpura
TTP has two main types: inherited and acquired
(noninherited) TTP.
Inherited means the condition is passed
from parents to children. This type of TTP mainly affects newborns and
children. In inherited TTP, the ADAMTS13 gene is faulty and doesnt prompt
the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is
lacking or is changed.
Acquired TTP is the more common type.
Acquired means you arent born with the condition, but you
develop it. This type of TTP occurs mostly in adults, but it sometimes affects
children.
In acquired TTP, the ADAMTS13 gene isnt
changed. Instead, the body makes proteins called antibodies that block the
ADAMTS13 enzymes activity.
What triggers inherited and acquired TTP isnt
known, but some factors may play a role. These include:
- Diseases and conditions such as pregnancy,
cancer, HIV, infection, and lupus
- Medical procedures such as surgery and bone
marrow transplant
- Medicines such as chemotherapy, ticlopidine,
clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
Outlook
TTP is a rare condition. It can be fatal or cause
lasting damage, such as brain damage or stroke, if its not treated right
away. About 1,200 people develop acquired TTP each year in the United States.
TTP usually occurs suddenly and lasts for days and
weeks, but it can continue for months. Most people recover fully from TTP when
treated promptly. Relapses (or flareups) can occur in 30 to 60 percent of
people with acquired TTP. Many people with inherited TTP have frequent flareups
that need to be treated.
Treatments for TTP include infusions of fresh frozen
plasma and plasma exchange (also called plasmapheresis (PLAZ-ma-fe-RE-sis)).
These treatments have greatly improved the outlook of the disease.
Other Names for Thrombotic Thrombocytopenic
Purpura
Inherited Thrombotic Thrombocytopenic Purpura
- Familial thrombotic thrombocytopenic purpura
- Upshaw-Schulman syndrome (USS)
Acquired Thrombotic Thrombocytopenic Purpura
- Moschcowitz disease
- Microangiopathic hemolytic anemia
What Causes Thrombotic Thrombocytopenic Purpura?
A lack of activity in the ADAMTS13 enzyme (a type of
protein in the blood) causes thrombotic thrombocytopenic purpura (TPP). The
ADAMTS13 gene controls the enzyme, which is involved in blood clotting.
Not having enough enzyme activity causes platelets
to clump together, forming blood clots. In TTP, when blood clots form, there
are fewer platelets in the blood. This can cause bleeding into the skin
(purpura), drawn-out bleeding from cuts, and internal bleeding. It also causes
small blood clots to form suddenly throughout the body, including in the brain
and kidneys.
TTP also can cause red blood cells to break apart
faster than the body can replace them. This leads to
hemolytic
anemia.
Inherited Thrombotic Thrombocytopenic Purpura
In the inherited form of TTP, changes in the
ADAMTS13 gene affect the enzymes function. The gene doesnt prompt
the body to make a normal ADAMTS13 enzyme. As a result, enzyme activity is
lacking or is altered.
Inherited means that the condition is
passed from parents to children. In inherited TTP, a person is born with two
copies of the altered geneone from each parent. Most often, the parents
each have one copy of the altered gene, but have no signs or symptoms of the
disorder.
Acquired Thrombotic Thrombocytopenic Purpura
In the acquired type of TTP, the ADAMTS13 gene
isnt changed. Instead, the body makes proteins called antibodies that
block the ADAMTS13 enzymes activity.
Acquired means you arent born with
the condition, but you develop it.
Triggers for Thrombotic Thrombocytopenic
Purpura
What triggers TTP isnt known, but some factors
may play a role. These include:
- Diseases and conditions such as pregnancy,
cancer, HIV, infection, and lupus
- Medical procedures such as surgery and bone
marrow transplant
- Medicines such as chemotherapy, ticlopidine,
clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
Who Is At Risk for Thrombotic Thrombocytopenic
Purpura?
Thrombotic thrombocytopenic purpura (TTP) is a rare
condition. About 1,200 new cases occur each year in the United States.
Most cases of TTP are the acquired type. Acquired
TTP mostly occurs in adults, but it can affect children. The condition is seen
more often in women than in men.
Inherited TTP mainly affects newborns and children.
Most people who have inherited TTP begin to have symptoms soon after birth.
Some, however, dont have their first episode of disease until
theyre adults.
What triggers TTP isnt known, but some factors
may play a role. These include:
- Diseases and conditions such as pregnancy,
cancer, HIV, infection, and lupus
- Medical procedures such as surgery and bone
marrow transplant
- Medicines such as chemotherapy, ticlopidine,
clopidogrel, cyclosporine A, and hormone replacement therapy and estrogens
What Are the Signs and Symptoms of Thrombotic
Thrombocytopenic Purpura?
Signs and symptoms of thrombotic thrombocytopenic
purpura (TTP) are due to blood clots, a low platelet count, and damaged red
blood cells.
The signs and symptoms include:
- Purplish spots called purpura on the skin or
mucous membranes (such as on the mouth) due to bleeding under the skin
- Paleness or jaundice (a yellowish color of the
skin or eyes)
- Feeling tired or weak
- Fever
- A fast heart rate or feeling short of breath
- Headache, speech changes, confusion, coma,
stroke, or seizure
- A low amount of urine, or protein or blood in the
urine
If youve had TTP and have any of these signs
and symptoms, call your doctor right away.
How Is Thrombotic Thrombocytopenic Purpura
Diagnosed?
Your doctor will diagnosis thrombotic
thrombocytopenic purpura (TTP) based on your medical history, a physical exam,
and test results.
If TTP is suspected or diagnosed, a hematologist (a
doctor who specializes in blood diseases) will be involved in your care.
Medical History
Your doctor will ask about factors that may affect
TTP, such as:
- Diseases or conditions you may have, such as
pregnancy, cancer, HIV, infection, or lupus
- Previous medical procedures, such as a bone
marrow transplant
- Medicines you take, such as ticlopidine,
clopidogrel, cyclosporine A, chemotherapy, and hormone replacement therapy and
estrogens
Physical Exam
Your doctor will do a physical exam and look for
signs such as:
- Bruising and bleeding under your skin
- Fever
- Paleness or jaundice (a yellowish color of the
skin or eyes)
- A fast heart rate
- Speech changes or changes in awareness that can
range from confusion to loss of consciousness, or passing out
- Stroke or seizures
- Changes in urine
Diagnostic Tests
Your doctor also may order tests to help find out if
you have TTP.
Complete Blood Count
This test measures the number of red and white blood
cells and platelets in your blood. For this test, a small amount of blood is
drawn from a vein (blood vessel), usually in your arm.
If you have TTP, your platelet count will be low and
you will have a lower than normal number of red blood cells (anemia).
Blood Smear
For this test, a small amount of blood is drawn from
a vein, usually in your arm. Some of your blood is put on a glass slide. A
microscope is then used to look at your red blood cells. In TTP, the red blood
cells are torn and broken.
Platelet Count
This test counts the number of platelets in a blood
smear (see above). People with TTP have a lower than normal number of platelets
in their blood. This test is used with the blood smear to help diagnose
TTP.
Bilirubin Test
When red blood cells die, they release a protein
called hemoglobin (HEE-muh-glow-bin) into the bloodstream. The body breaks down
hemoglobin into a compound called bilirubin. High levels of bilirubin in the
bloodstream cause jaundice.
For this blood test, a small amount of blood is
drawn from a vein, usually in your arm. In TTP, bilirubin may be high because
your body is breaking down red blood cells at a faster than normal rate.
Kidney Function Tests and Urine Tests
These tests are done to see whether your kidneys are
working well. In TTP, your urine may contain protein or blood cells. Also your
blood creatinine level may be high. Creatinine is a blood product that normally
is removed by the kidneys.
Coombs Test
This blood test is used to see whether TTP is the
cause of
hemolytic
anemia. For this test, a small amount of blood is drawn from a vein,
usually in your arm.
In TTP, hemolytic anemia occurs when red blood cells
are broken into pieces as they try to squeeze around blood clots.
When TTP is the cause of hemolytic anemia, the
Coombs test is negative. It's positive when antibodies that bind to red blood
cells cause your immune system to destroy the cells.
Lactate Dehydrogenase Test
This blood test measures a protein called lactate
dehydrogenase (LDH). For this test, a small amount of blood is drawn from a
vein, usually in your arm.
Hemolytic anemia causes red blood cells to break and
release this protein into the blood. LDH also is released from tissues that are
injured by blood clots as a result of TTP.
ADAMTS13 Assay
A lack of activity of the ADAMTS13 enzyme causes
TTP. For this test, a small amount of blood is drawn from a vein, usually in
your arm. The blood is sent to a special lab to test for the enzyme's
activity.
How Is Thrombotic Thrombocytopenic Purpura
Treated?
Thrombotic thrombocytopenic purpura (TTP) can be
fatal or cause lasting damage, such as brain damage or stroke, if its not
treated promptly.
In most cases, TTP occurs suddenly and lasts for
days and weeks, but it can go on for months. Most people recover fully when
treated right away. Relapses (flareups) can occur in 30 to 60 percent of people
with acquired TTP. Flareups also occur in most people with inherited TTP.
Plasma treatments are the most common way to treat
TTP. Other treatments include medicines and surgery. Treatments are done in a
hospital.
Plasma Therapy
Plasma is the liquid part of your blood. It carries
blood cells, hormones, enzymes, and nutrients to your body.
TTP is treated with plasma therapy. This includes
fresh frozen plasma for newborns and children with inherited TTP, and plasma
exchange for people with acquired TTP. Plasma therapy is started in the
hospital as soon as TTP is diagnosed or suspected.
For inherited TTP, fresh frozen plasma is given
through an intravenous (IV) line in a vein (blood vessel). This is done to
replace the missing or changed ADAMTS13 enzyme.
For acquired TTP, plasma exchange (also called
plasmapheresis) is done. This is a lifesaving procedure. It removes antibodies
from the blood that damage your ADAMTS13 enzyme. It also replaces the ADAMTS13
enzyme. If plasma exchange isnt available, you may be given fresh frozen
plasma until it is available.
During plasma exchange, an IV needle or tube is
placed in your arm to remove blood. The blood then goes through a cell
separator, which removes plasma from the blood. The nonplasma part of the blood
is saved, and donated plasma is added to it.
The blood is then put back into you through an IV
line in one of your blood vessels. The time the procedure takes varies, but it
often takes about 2 hours.
Treatments of fresh frozen plasma or plasma exchange
usually continue until your blood tests and signs and symptoms improve. This
can be days or weeks depending on your condition. You will stay in the hospital
during this time.
Some people who recover from TTP have flareups. This
can happen in the hospital or after you go home. If you have a flareup, plasma
infusion or plasma exchange will be restarted.
Other Treatments
Other treatments are used when plasma infusions or
plasma exchange doesnt work well or when flareups occur often.
Medicines are used to slow or stop antibodies from
forming. In acquired TTP, antibodies block the activity of the ADAMTS13 enzyme.
Medicines used to treat TTP include glucocorticoids, vincristine, rituximab,
and cyclosporine A.
Surgery to remove the spleen (an organ in the
abdomen) is sometimes needed. This is because cells in the spleen make
antibodies that block the activity of the ADAMTS13 enzyme.
How Can Thrombotic Thrombocytopenic Purpura Be
Prevented?
Both inherited and acquired thrombotic
thrombocytopenic purpura (TTP) appear suddenly with no clear cause. You
cant prevent either type.
If youve had TTP, its important to watch
for signs and symptoms of a relapse (flareup). (See "Living With Thrombotic Thrombocytopenic
Purpura for more information.)
You also should talk to your doctor about factors
that may trigger TTP or a flareup, including:
- Diseases or conditions you may have, such as
pregnancy, cancer, HIV, infection, or lupus.
- Any prior medical procedures, such as a bone
marrow transplant.
- Medicines you may take, such as ticlopidine,
clopidogrel, cyclosporine A, chemotherapy, and hormone replacement therapy and
estrogens. Your doctor may change some of these medicines.
Living With Thrombotic Thrombocytopenic Purpura
Most people recover fully from thrombotic
thrombocytopenic purpura (TTP) when treated promptly. Relapses (or flareups)
can occur in 30 to 60 percent of cases.
If this happens, plasma therapy and/or medicines
will need to be restarted.
If youve had TTP, you should call your doctor
right away if you have signs or symptoms of a relapse. These signs and symptoms
include:
- Purplish spots called purpura on the skin or
mucous membranes (such as on the mouth) due to bleeding under the skin
- Unexplained or prolonged bleeding
- Paleness or jaundice (a yellowish color of the
skin or eyes)
- Feeling tired or weak
- Fever
- A fast heart rate or feeling short of breath
- Headaches, speech changes, confusion, coma,
stroke, or seizures
- A low amount of urine, or protein or blood in the
urine
If you have been successfully treated for TTP, you
should talk to your doctor about using any medicinessuch as aspirin and
ibuprofenthat can raise your risk of bleeding during a relapse. Also,
tell your doctor about all over-the-counter medicines you take, including
vitamins, supplements, or herbal remedies.
If your child has inherited TTP, ask the doctor
whether you need to restrict your childs activities.
Report any symptoms of infection, such as a fever,
to your doctor. This is very important for people who have had their spleens
removed.
Talk to your doctor about changing medicines that
may raise your risk for TTP, such as ticlopidine and clopidogrel.
Key Points
- Thrombotic thrombocytopenic purpura (TTP) is a
rare blood condition. It causes blood clots to form in small blood vessels
throughout the body. These blood clots can cause serious problems if they block
blood vessels and limit blood flow to the brain, kidneys, or heart.
- Blood clots form when blood cells called
platelets clump together. When this happens, there are fewer platelets in the
blood. This can cause bleeding into the skin (purpura), prolonged bleeding from
cuts, and internal bleeding.
- TTP also can cause red blood cells to break apart
faster than the body can replace them. This leads to
hemolytic
anemia.
- TTP has two main types: inherited and acquired.
Inherited TTP mainly affects newborns and children. Acquired TTP occurs mostly
in adults, but sometimes affects children.
- A lack of activity in the ADAMTS13 enzyme (a type
of protein in the blood) causes TTP. The ADAMTS13 gene controls the enzyme,
which is involved in blood clotting. Not having enough enzyme activity causes
platelets to clump together, forming blood clots.
- What triggers inherited and acquired TTP
isnt known, but some diseases or conditions, medical procedures, and
medicines may contribute to it.
- About 1,200 new cases of TTP occur each year in
the United States. Most cases of TTP are the acquired type. The condition is
seen more often in women than in men.
- Signs and symptoms of TTP include purplish spots
called purpura on the skin or mucous membranes, paleness or jaundice (a
yellowish color of the skin or eyes), fatigue (tiredness) and weakness, fever,
a fast heart rate or feeling short of breath, headache, speech changes,
confusion, coma, stroke, seizure, a low amount of urine, or protein or blood in
the urine. If you have any of these signs and symptoms, call your doctor right
away.
- A diagnosis of TTP is based on your medical
history, a physical exam, and test results.
- TTP is usually treated with infusions of fresh
frozen plasma or plasma exchange. Other treatments, such as medicines and
surgery, are used when plasma treatment doesnt work well or relapses
(flareups) occur often.
- Both inherited and acquired TTP appear suddenly
with no clear cause. You cant prevent either type.
- You should call your doctor right away if you
have signs or symptoms of a TTP flareup. These are the same as the initial
signs and symptoms of TTP.
- You also should report any symptoms of infection.
Talk to your doctor about changing medicines that may raise your risk for TTP
or bleeding.
- Most people recover fully from TTP when treated
promptly. Flareups can occur in 30 to 60 percent of people with acquired TTP.
They also occur in most people with inherited TTP.
Links to Other Information About Thrombotic
Thrombocytopenic Purpura
Non-NHLBI Resources
Clinical Trials
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