Thrombotic Thrombocytopenic Purpura (TTP) is a rare blood disorder where blood clots form in small blood vessels throughout the body, obstructing blood flow to vital organs. The condition is defined by two primary issues: the development of these small clots, known as thrombi, and a low count of platelets, the blood cells that help form clots to stop bleeding. TTP is a medical emergency that requires prompt diagnosis and treatment to prevent serious complications.
The Underlying Cause of TTP
The development of TTP is linked to an enzyme in the blood called ADAMTS13. This enzyme functions like molecular scissors, trimming a large protein known as von Willebrand factor (vWF) into smaller pieces to control blood clotting. When ADAMTS13 is deficient, vWF proteins remain unusually large, causing platelets to stick together and form unneeded clots within small blood vessels.
The condition is categorized into two main types based on why the enzyme is not working properly. The more common form is acquired TTP, where the body’s immune system produces antibodies that attack and block the ADAMTS13 enzyme. In rarer cases, an individual may have inherited TTP (Upshaw-Schulman syndrome), caused by a genetic mutation in the ADAMTS13 gene.
Recognizable Signs and Symptoms
Symptoms of TTP arise from widespread microscopic clots and a shortage of platelets. The clots can block blood flow to organs like the brain, heart, and kidneys, while the low platelet count can lead to bleeding. One of the most visible signs is purpura (purple-colored bruises) and petechiae (tiny red or purple dots that look like a rash), caused by spontaneous bleeding under the skin.
Individuals may also experience unexplained bleeding from the nose or gums. The destruction of red blood cells as they pass the clots leads to microangiopathic hemolytic anemia, causing fatigue, weakness, and pale skin. In some cases, the skin may develop a yellowish tone, a sign of jaundice.
A fever is another common symptom. Neurological issues can range from headache and confusion to seizures or stroke-like symptoms. The combination of bleeding with any change in mental status requires immediate medical evaluation.
The Diagnostic Process
Diagnosing TTP is urgent, and treatment often begins based on clinical suspicion before all lab results are confirmed. The initial evaluation involves a complete blood count (CBC) to confirm a low platelet count (thrombocytopenia) and check for anemia.
An examination of a peripheral blood smear under a microscope is also performed. This test reveals the presence of schistocytes, which are fragmented red blood cells damaged by passing the tiny clots. Doctors also test for elevated levels of lactate dehydrogenase (LDH) as evidence of cell damage.
The most definitive test is an ADAMTS13 activity assay. This specialized blood test measures the level of functional ADAMTS13 enzyme. A result showing severely deficient activity, below 10% of normal levels, confirms the diagnosis of TTP.
Primary Treatment Methods
The primary treatment for acquired TTP is a procedure called plasma exchange, or plasmapheresis. During this process, a machine separates the patient’s plasma, which contains the harmful anti-ADAMTS13 antibodies, from their blood cells. The patient’s plasma is removed and replaced with fresh donor plasma, which replenishes the body’s supply of the functional ADAMTS13 enzyme.
To address the root cause of acquired TTP, treatments are used to suppress the immune system’s attack on the ADAMTS13 enzyme. Corticosteroids are commonly administered to reduce the production of these antibodies. For a more targeted approach, a monoclonal antibody medication called rituximab may be used, which specifically targets and destroys the B-cells responsible for producing the antibodies.
Newer medications provide more direct intervention. Caplacizumab is a therapeutic agent that works by preventing the von Willebrand factor protein from binding to platelets. This action directly inhibits the formation of the microvascular clots that characterize the disease.
Prognosis and Relapse Management
With modern treatments like plasma exchange, the outlook for individuals with TTP has improved. If treatment is initiated quickly, the survival rate for an acute episode is now over 90%, a major change from the pre-treatment era when the condition was almost always fatal.
Despite successful initial treatment, acquired TTP has the potential to return, an event known as a relapse. Because of this risk, long-term follow-up is part of managing the condition. Patients undergo regular monitoring, which includes blood tests to check their platelet counts and ADAMTS13 enzyme activity levels, allowing doctors to detect a drop in enzyme activity before a clinical relapse occurs.
If ADAMTS13 levels fall to a low point, physicians may initiate pre-emptive treatment. This often involves therapies like rituximab to stop the immune system’s renewed attack and prevent the recurrence of symptoms. This approach helps transform TTP into a manageable, though serious, chronic condition for many survivors.