Thrombotic Thrombocytopenic Purpura (TTP) is a rare and serious blood disorder that can develop suddenly, making prompt recognition and intervention important. This article focuses on acquired TTP, explaining its mechanisms, presentation, diagnosis, and treatment.
What is Acquired Thrombotic Thrombocytopenic Purpura?
Acquired TTP, also known as immune-mediated TTP, is a life-threatening blood disorder characterized by the widespread formation of tiny blood clots in small blood vessels throughout the body. These microvascular clots can lead to tissue ischemia and organ damage. The root cause of acquired TTP lies in a severe deficiency of an enzyme called ADAMTS13.
Normally, ADAMTS13 is responsible for cleaving ultra-large von Willebrand factor (ULvWF) multimers, which are large proteins involved in blood clotting. Without sufficient ADAMTS13 activity, these ULvWF multimers accumulate and spontaneously bind to platelets, leading to the formation of platelet-rich microthrombi. This excessive clotting consumes platelets, resulting in a low platelet count (thrombocytopenia), and also damages red blood cells as they pass through the narrowed vessels, causing a type of anemia called microangiopathic hemolytic anemia. The deficiency in ADAMTS13 activity in acquired TTP is due to autoantibodies that inhibit the enzyme’s function or accelerate its clearance.
Recognizing the Signs
The signs and symptoms of acquired TTP can be varied and often nonspecific, making early diagnosis challenging. These symptoms are directly linked to the widespread microclots and the resulting low platelet count and red blood cell destruction. Neurological symptoms are commonly observed, including headaches, confusion, seizures, and stroke-like symptoms.
Patients may experience kidney problems, though renal involvement is less frequent in TTP. Other common signs include fever, abdominal pain, and general fatigue. Bleeding due to the low platelet count is typical, presenting as tiny red or purple spots on the skin called petechiae, larger purplish bruises known as purpura, or bleeding from the nose or gums.
How Acquired TTP is Diagnosed
Diagnosing acquired TTP involves a combination of clinical assessment and specific laboratory tests. A healthcare provider begins with a thorough review of the patient’s medical history and a physical examination, looking for signs such as pale skin or bruising. Initial blood tests, particularly a complete blood count (CBC), reveal a low platelet count (below 30 x 10^9/L) and evidence of hemolytic anemia, indicated by fragmented red blood cells (schistocytes) on a blood smear.
The definitive diagnosis of acquired TTP hinges on measuring the activity of the ADAMTS13 enzyme. A severe deficiency, defined as ADAMTS13 activity less than 10% of normal, is highly suggestive of TTP. Tests are performed to detect ADAMTS13 inhibitors, which are the autoantibodies responsible for the enzyme’s dysfunction in acquired TTP. While ADAMTS13 activity results may take some time to return, clinical judgment based on initial blood work and symptoms can guide the initiation of treatment.
Treatment Approaches
The primary treatment for acquired TTP is plasma exchange (plasmapheresis). This procedure involves removing the patient’s plasma, which contains the harmful autoantibodies and ultra-large von Willebrand factor multimers, and replacing it with healthy donor plasma containing functional ADAMTS13. Plasma exchange has significantly improved survival rates for patients with TTP, increasing them from less than 10% to approximately 80%.
Alongside plasma exchange, immunosuppressive therapies are administered to suppress the immune system’s production of autoantibodies against ADAMTS13. Corticosteroids, such as prednisone, are commonly used. Rituximab, a monoclonal antibody that targets B lymphocytes, is also used, either as part of the initial treatment regimen or for patients who do not respond to plasma exchange and corticosteroids. Rituximab can help achieve remission and reduce the likelihood of relapse.
Navigating Recovery and Long-Term Health
After an acute episode of acquired TTP, patients require ongoing monitoring and management due to the potential for relapse and long-term complications. Lifelong follow-up is recommended for all recovered patients. Regular blood tests, including complete blood counts and lactate dehydrogenase (LDH) levels, are performed during the initial recovery period to detect any signs of exacerbation or relapse.
Monitoring ADAMTS13 activity levels periodically is standard practice, as a decrease in activity (less than 10 IU/dL) can indicate an increased risk of relapse and may prompt preemptive therapy. Patients are educated about the signs and symptoms of recurrence to facilitate early detection and prompt intervention. While the risk of relapse is highest in the first two years, recurrences can happen many years later.