What is TTP also known as? Distinguishing the different names
Thrombotic Thrombocytopenic Purpura (TTP) is a complex medical condition, and its classification has evolved over time with increased understanding of its causes. This has led to several alternative names and descriptors that provide more specific information about the disease. For instance, TTP is historically known as Moschcowitz syndrome or Moschcowitz disease after the physician who first described it in 1924. This historical name is a reminder of the initial characterization of the illness before the underlying enzymatic defect was discovered. A more general term is Thrombotic Microangiopathy (TMA), which is a broad group of disorders, including TTP, characterized by the formation of blood clots in small blood vessels.
For the inherited form, a specific name exists: Upshaw-Schulman syndrome. This describes the rare, congenital type of TTP where a genetic mutation causes a lifelong deficiency of the ADAMTS13 enzyme. The much more common acquired form of TTP is often called immune-mediated TTP (iTTP) or autoimmune TTP, because it is caused by the immune system mistakenly producing antibodies that attack and block the ADAMTS13 enzyme. If the acquired form lacks a clear trigger, it may also be termed idiopathic TTP. Understanding these different names is key to recognizing the specific variant of TTP a patient may have.
The root cause: ADAMTS13 deficiency
The core mechanism behind TTP is a severe deficiency in the activity of the enzyme ADAMTS13. This enzyme, which stands for 'a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13', plays a critical role in blood clotting. Its job is to cleave or cut large, string-like proteins called von Willebrand factor (VWF) multimers into smaller, normal-sized pieces. When ADAMTS13 activity falls below 10% of its normal level, these unusually large VWF multimers accumulate. These oversized multimers become excessively sticky, spontaneously binding to platelets and causing them to clump together and form microthrombi, or tiny blood clots. These clots are the root cause of the organ damage and other symptoms associated with TTP.
The two forms of TTP
As previously mentioned, TTP primarily presents in two distinct forms, which are differentiated by their cause.
- Acquired TTP (aTTP) / Immune-mediated TTP (iTTP): This is the most common form, accounting for the vast majority of cases. It develops when the body's immune system produces autoantibodies that target and inhibit ADAMTS13. A specific cause for this immune attack is often not identified, leading to the designation 'idiopathic', but it can be triggered by infections (including HIV and COVID-19), certain medications (e.g., clopidogrel), autoimmune diseases like lupus, pregnancy, or surgery.
- Hereditary TTP / Upshaw-Schulman syndrome: This rare form is caused by a genetic mutation in the ADAMTS13 gene, resulting in a non-functional enzyme from birth. While present from birth, symptoms may not appear until adulthood, often triggered by an event like infection or pregnancy.
Signs, symptoms, and diagnosis
The signs and symptoms of TTP arise from the formation of microthrombi and the resulting damage to blood cells and organs. While a classic pentad of symptoms (fever, neurologic changes, thrombocytopenia, renal failure, and hemolytic anemia) was once used for diagnosis, it is now known that fewer than 10% of patients present with all five. The most consistent findings are severe thrombocytopenia and microangiopathic hemolytic anemia, which are key indicators for a presumptive diagnosis.
Common symptoms include:
- Bleeding problems: Due to a dangerously low platelet count (thrombocytopenia), patients may experience easy bruising (purpura) and tiny red or purple spots on the skin (petechiae).
- Neurological issues: Blood clots in the brain can cause a wide range of symptoms, including headaches, confusion, slurred speech, seizures, and in severe cases, coma.
- Anemia and fatigue: The mechanical shearing of red blood cells by the microthrombi causes hemolytic anemia, leading to paleness, extreme fatigue, and shortness of breath.
- Organ dysfunction: The tiny clots can obstruct blood flow to other organs, including the kidneys, heart, and pancreas, causing kidney problems, chest pain, and abdominal issues.
Diagnosis requires a high index of suspicion and is confirmed with laboratory tests. The most definitive test measures ADAMTS13 activity, with a level below 10% being highly indicative of TTP. Other blood tests evaluate for signs of hemolysis (e.g., high LDH and bilirubin), low platelet count, and the presence of red blood cell fragments (schistocytes) in a blood smear.
TTP vs. HUS: A critical distinction
It is crucial to distinguish TTP from Hemolytic Uremic Syndrome (HUS), another type of thrombotic microangiopathy that can have overlapping symptoms but requires different treatment strategies. The primary differentiating factor is the level of ADAMTS13 activity, along with the patient's typical presentation.
| Feature | Thrombotic Thrombocytopenic Purpura (TTP) | Hemolytic Uremic Syndrome (HUS) |
|---|---|---|
| Primary Cause | Severe deficiency (<10%) of the ADAMTS13 enzyme. | Caused by infection with a Shiga toxin-producing bacteria, like E. coli O157:H7, or by complement system genetic abnormalities. |
| ADAMTS13 Activity | Severely deficient. | Usually normal or only mildly reduced. |
| Typical Patient | More common in adults, especially women. | More common in children. |
| Dominant Features | Often more prominent neurological symptoms. | Primarily affects the kidneys, causing more severe renal impairment. |
| Treatment | Plasma exchange, immunosuppressants, and newer targeted therapies like caplacizumab. | Supportive care; plasma exchange is not typically the first-line treatment. |
Treatment strategies for TTP
Since TTP is a medical emergency, immediate and aggressive treatment is essential to reduce the high risk of mortality. The cornerstone of treatment for acquired TTP is therapeutic plasma exchange (PEX), also known as plasmapheresis. During PEX, the patient's plasma, containing the harmful autoantibodies, is removed and replaced with healthy donor plasma that provides the necessary ADAMTS13 enzyme.
In addition to PEX, other treatments are used to target the immune system and prevent relapse:
- Corticosteroids: These immunosuppressants are often given alongside PEX to suppress the autoantibody production.
- Rituximab: A monoclonal antibody that targets B-cells (the source of the autoantibodies), rituximab is used for refractory or relapsing cases.
- Caplacizumab: A newer drug that blocks the interaction between large VWF multimers and platelets, preventing clot formation.
- For inherited TTP: Patients receive regular infusions of fresh frozen plasma to replace the deficient ADAMTS13.
- Other options: In rare, severe cases that don't respond to other therapies, a splenectomy (surgical removal of the spleen, where autoantibodies are made) might be considered.
Conclusion
Thrombotic Thrombocytopenic Purpura (TTP) is a rare but critical blood disorder that is also known by names such as Moschcowitz syndrome, Upshaw-Schulman syndrome, and immune-mediated TTP, reflecting its different forms and history. At its root, TTP is caused by a severe deficiency of the ADAMTS13 enzyme, leading to the formation of microthrombi and subsequent organ damage. Prompt and accurate diagnosis, often differentiated from similar conditions like HUS through ADAMTS13 level testing, is paramount. With modern treatments like plasma exchange and targeted immune therapies, the once-fatal disease now has a greatly improved prognosis. However, vigilance for relapse and long-term monitoring remain vital for affected individuals. More information on TTP and other rare blood disorders can be found at the National Organization for Rare Disorders (NORD), a resource dedicated to supporting and educating patients and healthcare providers.
