Thrombotic Thrombocytopenic Purpura

Blood Clot
Blood Clot. Science Photo Library - STEVE GSCHMEISSNER/Brand X Pictures/Getty Images

Definition

Thrombotic Thrombocytopenic Purpura (TTP) is a rare life-threatening blood disorder causing small thrombi (clots) to form in the blood vessels.  TTP results from low levels of ADAMTS13, an enzyme (protein) that helps to break down von Willebrand factor (vWF).  When vWF is not broken down appropriately, it clumps with platelets causing clots to form.  This causes the number of platelets circulating to drop (called thrombocytopenia).

 

Symptoms of TTP

Symptoms are related to the low platelet count which causes bleeding and blocked blood flow from clots forming in blood vessels.

  • Bleeding under the skin called petechiae (pinpoint red dots) and purpura (bruises)
  • Bleeding from nose or mouth
  • Fatigue secondary to anemia
  • Fever
  • Neurological changes:  These vary greatly and include: confusion, headache, seizure
  • Dark urine
  • Jaundice (yellowing of the skin)

Types of TTP 

Congenital (or inherited) TTP:  As the name suggests, a person is born with this form of TTP.  This is caused by a decreased amount of the ADAMTS13 enzyme being produced by the body.  

Acquired TTP:  Acquired TTP can either be idiopathic (a cause cannot be found) or secondary TTP meaning it is caused by another condition or medications.  These include pregnancy, chemotherapy, cancer, hepatitis, HIV, medications (cyclosporine, quinine, etc), autoimmune disease, and bone marrow transplantation.

 In general, acquired TTP occurs when the body develops an antibody to ADAMTS13, resulting in destruction of this enzyme. 

Diagnosis

The two most helpful tests to diagnose TTP are a complete blood count (CBC) and a peripheral blood smear.  The CBC identifies both anemia and thrombocytopenia.  The peripheral blood smear reveals schistocytes, fragmented red blood cells.

 The red blood cells are fragmented as they are cut by the small clots in the blood.  This is called a hemolysis, destruction of the red blood cells.    

Another test commonly used is a lactate dehydrogenase (LDH).  LDH is an enzyme found red blood cells (as well as other cells in the body).  LDH levels go up during hemolysis.  An elevated LDH in the presence of anemia, thrombocytopenia, and schistocytes is consistent with TTP.

Testing can be sent to measure an ADAMTS13 enzyme level and an ADAMTS13 inhibitor (antibody) level.  These are consider confirmatory testing and not mandatory for diagnosis. Treatment should not be held while awaiting results. 

Treatment

Congenital TTP is treated with infusions of fresh frozen plasma.  Plasma from donors without TTP has normal levels of the ADAMTS13 enzyme.  

Acquired or idiopathic TTP is treated with a combination of treatments.

  • Therapeutic plasma exchange (TPE):  Tis is also called plasmapheresis.  TPE uses a machine to remove plasma from the patient (containing the antibody against ADAMTS13) and replaces it with fresh frozen plasma (containing normal amounts of ADAMTS13).  TPE is repeated daily until symptoms (i.e., neurological symptoms resolve) and laboratory data (increased platelet count, decrease in LDH) improve.  It is then weaned as tolerated.  Length of treatment is very patient specific.  
  • Steroids:  Steroids like prednisone and methylprednisolone are used to reduce the body's immune response (the production of ADAMTS13 antibodies).  These are generally initiated during TPE and slowly weaned over several weeks.
  • Rituximab:  This may be used for patients who have a poor response to TPE or who relapse after remission.  Rituximab helps to remove the B-cells (a white blood cell that produces antibodies) temporarily.  When the body is able to make B-cells again, the hope is that they will no longer produce the antibody to ADAMTS13.

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