Thrombotic Thrombocytopenic Purpura (TTP)
Characteristics
Thrombotic thrombocytopenic purpura (TTP) is a rare, but life-threatening blood disorder in which blood clots form in small blood vessels throughout the body. These clots limit or block the blood flow to vital organs, such as the brain, kidneys, or heart. The resulting lack of oxygen prevent organs from working properly, ultimately leading to organ damage. Furthermore, the formation of blood clots throughout the body uses up large amounts of platelets. As a result, patients may not have enough platelets to form blood clots when necessary, leading to bleeding episodes and bruising.
TTP can be inherited or acquired. In patients with inherited TTP the disease is passed down from parents to children due to variants in the ADAMTS13 gene. This gene encodes for the ADAMTS13 enzyme, which plays an important role in controlling the blood clotting process. In the majority of patients, however, the TTP is acquired, which means that it develops later in life. Acquired TTP develops when the body mistakenly makes antibodies that block the activity of the ADAMTS13 enzyme.
While TTP can affect people of all ages, it most frequently occurs in people aged 20 to 50 years old. Furthermore, pregnancy and HIV are associated with a higher risk for the development of TTP.
Symptoms
The symptoms of TTP may develop suddenly and are generally caused by the development of blood clots, a low platelet count, and damaged red blood cells. The most common symptoms include the development of small, flat red spots under the skin (petechiae) caused by blood leaking from blood vessels (petechiae) and the formation of red, purple, or brownish-yellow spots caused by bleeding in the skin (purpura).
TTP may also lead to paleness, a yellowish color of the skin or whites of the eyes (jaundice), extreme tiredness, fever, a fast heart rate and shortness of breath. When the blood flow to the brain is impacted, TTP can be associated with (severe) headaches, speech changes, confusion, coma, stroke, or seizure. In addition to this, TTP may cause nausea, vomiting, or diarrhea.
Diagnostic tests
When there is a suspicion of TTP, a number of diagnostic test will be performed. This includes a complete blood count to evaluate the number of blood platelets, a blood smear to evaluate the shape of red blood cells and urine tests to see if the kidney is functioning properly. Other tests, such as a bilirubin and a lactate dehydrogenase test, are performed to assess whether there is an excessive breakdown of red blood cells.
As TTP is caused by a lack of ADAMTS13 activity, the diagnostic work-up for TTP also includes an ADAMTS13 assay. For this test, a sample of blood is drawn from a vein, and sent to a special lab to evaluate the enzyme’s activity.
Treatments
The standard of care for patients with TTP consists of intravenous plasma exchange. In the procedure, blood is removed from the body and passed through a centrifuge to remove the abnormal plasma. In a second step, healthy plasma is added to the blood after which it is re-infused in the patient.
For patients with acquired TTP who do not respond properly to plasma exchange, medication that suppresses the immune system (i.e., corticosteroids or the monoclonal antibody rituximab). The goal of these therapies is to prevent the formation of anti-ADAMTS13 antibodies.
More recently, also a nanobody called caplacizumab has been approved for the treatment of acquired TTP. This nanobody blocks the function of a specific blood clotting protein, preventing the formation of the typical TTP microthrombi.
In rare cases, a splenectomy (i.e., surgical removal of the spleen) is performed in patients who are refractory to the other treatment options.
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