Thrombotic Thrombocytopenic Purpura (TTP) is a rare but potentially life-threatening blood disorder that is characterized by the formation of small blood clots (thrombi) in small blood vessels throughout the body, leading to low platelet count (thrombocytopenia), hemolysis (destruction of red blood cells), and organ damage.
It is a form of microangiopathic hemolytic anemia, meaning the blood clots damage the red blood cells as they pass through the small blood vessels, leading to fragmented cells, which can further contribute to the condition.
Key Features of TTP:
- Thrombocytopenia: Low platelet count, which can result in easy bruising and bleeding.
- Hemolytic anemia: Destruction of red blood cells, leading to fatigue and jaundice.
- Microthrombi: Abnormal blood clots form in small blood vessels, potentially obstructing blood flow to vital organs such as the brain, kidneys, and heart.
Causes of Thrombotic Thrombocytopenic Purpura
TTP occurs when there is a deficiency or dysfunction of an enzyme called ADAMTS13. This enzyme is responsible for breaking down a protein called von Willebrand factor (vWF), which helps blood clot. Without enough ADAMTS13, large vWF molecules promote the formation of small clots in the blood vessels, which causes the primary symptoms of TTP.
There are two forms of TTP:
- Acquired TTP:
- This is the most common form and occurs when the immune system produces antibodies that attack and inhibit the ADAMTS13 enzyme.
- It is often triggered by factors such as infections, medications (e.g., quinine or chemotherapy drugs), autoimmune diseases, or pregnancy.
- Idiopathic acquired TTP occurs without a clear known cause and is thought to be an immune system dysfunction.
- Inherited TTP (Upshaw-Schulman Syndrome):
- This is a genetic form of TTP, where the ADAMTS13 gene is mutated, leading to an enzyme deficiency.
- It is much rarer and typically presents in childhood, though symptoms can vary.
Symptoms of Thrombotic Thrombocytopenic Purpura
Symptoms typically develop suddenly and may include:
- Purpura: Purple or red spots on the skin caused by bleeding under the skin.
- Petechiae: Small, pinpoint red or purple spots from broken capillaries.
- Fatigue: Due to anemia from the destruction of red blood cells.
- Easy bruising or excessive bleeding.
- Neurological symptoms: These can include confusion, headache, seizures, and stroke-like symptoms (due to clots blocking blood flow to the brain).
- Fever: Common in TTP cases.
- Kidney damage: Reduced urine output, dark urine, or swelling due to kidney involvement.
- Jaundice: Yellowing of the skin or eyes caused by hemolysis (destruction of red blood cells).
- Chest pain: Associated with potential clots affecting the heart.
Diagnosis of Thrombotic Thrombocytopenic Purpura
Diagnosis is based on clinical symptoms, laboratory tests, and exclusion of other conditions. Key diagnostic steps include:
- Blood tests:
- Platelet count: Low platelet count is a hallmark of TTP.
- Lactate dehydrogenase (LDH): Elevated levels indicate tissue damage and hemolysis.
- ADAMTS13 activity test: A low level of ADAMTS13 confirms TTP.
- Schistocytes on blood smear: Fragmented red blood cells that indicate microangiopathic hemolytic anemia.
- Haptoglobin levels: Low levels suggest red blood cell destruction.
- Other tests:
- Coagulation studies like PT (prothrombin time) and aPTT (activated partial thromboplastin time) are typically normal in TTP, which helps differentiate it from other clotting disorders.
Treatment of Thrombotic Thrombocytopenic Purpura
TTP is a medical emergency and requires prompt treatment. The main treatment options include:
- Plasma exchange (plasmapheresis): This is the most important treatment for TTP. The procedure involves removing the patient's plasma, which contains the harmful antibodies, and replacing it with donor plasma. This helps restore ADAMTS13 activity and reduces clotting.
- Immunosuppressive therapy: Drugs like corticosteroids (e.g., prednisone) and rituximab (a monoclonal antibody) may be used to reduce the immune system's attack on ADAMTS13.
- Platelet transfusions: These are usually avoided as they may worsen clotting. However, in rare cases of severe bleeding, they may be administered.
- Supportive care: This may include blood transfusions, kidney dialysis (if there is kidney failure), and medications to manage complications, such as seizures or hypertension.
Prognosis
- Acquired TTP: If treated early with plasma exchange and immunosuppressive therapy, the prognosis is often good. However, if untreated, TTP can lead to serious complications, including organ failure, neurological deficits, and death.
- Inherited TTP: Treatment is generally more challenging and may involve ongoing plasma exchange to prevent relapses. With appropriate care, many people with inherited TTP can lead relatively normal lives, but they may experience frequent episodes.
