Thrombotic Thrombocytopenic Purpura

(TTP; Moschcowitz Syndrome)

Definition

Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder. It makes blood clot in the small blood vessels all over the body. These small clots can block the flow of blood to major organs, such as the kidneys, brain, or heart.
Excessive clotting with TTP uses up platelets causing low levels of platelets, which makes bleeding more likely. This leads to bruising and purpura, a rash made of purple or red spots.
There are 2 types of TTP:
  • Acquired—more common, resulting from other causes
  • Inherited—present from birth
TTP is serious and requires treatment right away. It may occur once or repeat in flare ups that can last from a few days to a few months.

Causes

Blood clotting is managed by a number of factors. One such factor is a type of enzyme that breaks down the protein which prevents excess clotting. Low levels of this enzyme, faulty enzymes, or delay with the enzyme, leads to the extreme clotting associated with TTP.
People with acquired TTP have normal enzymes, but their activity is blocked or slowed by outside factors. It may be triggered by medical treatments or infections, especially those that affect the immune system. Normally, the immune system creates antibodies to fight foreign matter in the body like germs. However, sometimes these antibodies can affect healthy tissue. With TTP, the antibodies block the action of the enzymes.
Inherited TTP is caused by a defect of a specific gene. The defect prevents the body from creating the enzyme or creating effective enzymes.

Risk Factors

TTP is more common in females and in young adults. Inherited TTP is more likely to show up in babies or children.
Health conditions that may be associated with TTP include:
Medical procedures or treatments that are associated with TTP include:
  • Bone marrow or stem cell transplants
  • Medications, such as:
    • Antiplatelet or anticoagulant drugs—block blood clot growth
    • Chemotherapy—used to treat cancer
    • Immunosuppressants—reduces the effects of the immune system on the body
    • Hormone therapies—used to treat certain health conditions or the effects of aging
    • Quinine—found in certain medications and health products

Symptoms

Symptoms can appear when TTP first begins or during a flare-up. Many symptoms occur because of damage to platelets and red blood cells caused by extreme clotting. Damage to platelets can cause bleeding problems. Damage to the red blood cells can lead to anemia and difficulty bringing oxygen in the blood. Other symptoms will depend on which organs are affected by the blood clots.
General symptoms may include:
  • Bruising (purpura) or red spots (petechiae)
  • Fatigue
  • Fever
  • Rapid heart rate
  • Trouble breathing
  • Gastrointestinal problems—abdominal pain, vomiting, nausea, and/or bloody diarrhea
  • Hematuria—blood in the urine
  • Jaundice—yellowing of skin and whites of eyes
  • Neurological problems—hallucinations, headache, numbness, paralysis, and changes in behavior or mental state
  • Fever
Red Blood Cells
Nucleus factsheet image
Red blood cell damage can cause fatigue and anemia.
Copyright © Nucleus Medical Media, Inc.

Diagnosis

The doctor will ask about your symptoms and medical history, looking for conditions or medications that may be related to symptoms. A physical exam will be done with careful exam of bruises or other blood under the skin.
Blood tests will be done to:
  • Assess the number of platelets, red blood cells, and other blood cells
  • Look for signs of damage to red blood cells (hemolysis) and anemia
  • Assess clotting status
  • Assess kidney and liver function
Other tests may be done if you have symptoms of damage to kidneys, liver, brain, or heart.

Treatment

TTP requires treatment right away to prevent damage to major organs from blood clots and manage damage to blood cells. Left untreated, TTP can lead to serious concerns such as kidney failure or stroke. You may be referred to a hematologist who specializes in blood disorders.
TTP can be managed by removing the antibodies causing the problem and/or adding the missing enzyme. TTP may occur once and not come back or there may be repeated flare ups.

Plasma Therapy

Plasma is the fluid part of blood. It contains many products including the enzyme related to TTP, as well as antibodies. Exchanging the plasma can help remove harmful antibodies and add missing enzymes. This process, also called plasmapheresis, is done by passing blood out of the body into a machine. The machine separates plasma from the blood cells and mixes the blood cells with donated, healthy plasma. The combined blood is then returned to the body.
If plasma exchange is not available right away, a plasma infusion may be used. Donated plasma will be passed into the blood flow through an IV. This plasma may provide the missing enzymes.
Plasma infusion or plasma exchange is started as soon as TTP is suspected. The therapy will be delivered until symptoms stop and blood tests show the condition is under control. Hospitalization is needed until therapy is complete and the risk of severe complications has passed. Therapy may need to be delivered over days or weeks.

Medications

The primary treatment for TTP is plasma therapy. TTP that does not fully respond to plasma therapy or TTP that has frequent flare ups may also be treated with medication. Medications may assist recovery by:
  • Slowing destruction of red blood cells
  • Stimulating the bone marrow to increase platelet production
  • Suppressing the immune system to decrease antibodies, for example with corticosteroids

Surgery

Splenectomy is an option for those with acquired TTP who do not respond to treatments or have repeated flare ups. The spleen is a small organ under the rib cage on the left side of the body. It is where high numbers of lymphocytes (a type of white blood cell) that make the antibodies that delay the clotting process are focused. Removing the spleen deters the growth of those antibodies.

Prevention

There are no current guidelines to prevent TTP because the cause is unknown.

RESOURCES

American Society of Hematology http://www.hematology.org

National Heart, Lung, and Blood Institute http://www.nhlbi.nih.gov

CANADIAN RESOURCES

Canadian Blood Services https://www.blood.ca

Public Health Agency of Canada http://www.phac-aspc.gc.ca

References

Explore thrombotic thrombocytopenic purpura. National Heart, Lung, and Blood Institute website. Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/ttp. Updated March 21, 2014. Accessed March 8, 2016.

Schaller M, Vogel M, Kentouche K, Lammie B, Kremer Hovinga JA. The splenic autoimmune response to ADAMTS13 in thrombotic thrombocytopenic purpura contains recurrent antigen-binding CDR3 motifs. Blood. 2014;134(23):3469-3479.

Thrombotic thrombocytopenic purpura. Genetics Home Reference website. Available at: https://ghr.nlm.nih.gov/condition/thrombotic-thrombocytopenic-purpura. Updated March 7, 2016. Accessed March 8, 2016.

Thrombotic thrombocytopenic purpura (TTP). EBSCO DynaMed Plus website. Available at: http://www.dynamed.com/topics/dmp~AN~T115863/Thrombotic-thrombocytopenic-purpura-TTP. Updated August 15, 2014. Accessed March 8, 2016.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS). Merck Manual Professional Version website. Available at: http://www.merckmanuals.com/professional/hematology-and-oncology/thrombocytopenia-and-platelet-dysfunction/thrombotic-thrombocytopenic-purpura-ttp-and-hemolytic-uremic-syndrome-hus. Updated September 2014. Accessed March 8, 2016.

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