Thrombocytopenic purpura (TTP)

Thrombocytopenic Purpura (TTP) is a rare but serious blood disorder characterized by a low platelet count (thrombocytopenia) and the formation of small blood clots throughout the body. These blood clots can obstruct the small blood vessels, leading to organ damage and other severe complications. TTP can be either acquired or inherited, with the acquired form being more common.

Types of Thrombocytopenic Purpura

1. Acquired TTP (also known as adult TTP or idiopathic TTP):
   • This is the most common form and usually occurs in adults.
   • It is often associated with an immune system malfunction where the body produces antibodies that destroy a protein called ADAMTS13, which is responsible for regulating blood clotting.
   • Without enough ADAMTS13, large clots form abnormally in small blood vessels throughout the body, leading to tissue and organ damage.
   • Acquired TTP can be triggered by infections, medications, or pregnancy, though it often occurs without a known cause.
2. Inherited TTP (also known as Upshaw-Schulman syndrome):
   • This rare genetic form is caused by mutations in the ADAMTS13 gene, leading to a deficiency or dysfunction of the ADAMTS13 enzyme.
   • Inherited TTP typically begins in childhood, though symptoms can vary widely in severity.

Causes and Risk Factors

TTP occurs when there is a deficiency of the ADAMTS13 enzyme, which is needed to break down large molecules of von Willebrand factor (vWF). When ADAMTS13 levels are low, large vWF molecules lead to the abnormal clotting of blood in small vessels. This can cause organ damage, especially in the kidneys, brain, and heart.

Common triggers and risk factors for acquired TTP include:

• Infections: Such as HIV, shingles, and bacterial infections (e.g., Shiga toxin-producing E. coli).
• Medications: Certain drugs, such as quinine, platinum-based chemotherapy, and clopidogrel (a blood-thinning medication), can trigger TTP.
• Pregnancy: TTP can occasionally occur during pregnancy, especially in the third trimester or after childbirth.
• Autoimmune disorders: Such as systemic lupus erythematosus (SLE), can be associated with TTP.
• Cancer: Some forms of cancer, particularly solid tumors, may increase the risk of TTP.

Symptoms of Thrombocytopenic Purpura

The symptoms of TTP can develop suddenly and may include:

• Purpura: Small purple or red spots (bruising) on the skin, caused by bleeding under the skin.
• Petechiae: Tiny red or purple spots on the skin caused by small blood vessel ruptures.
• Fatigue: Due to low platelet levels and anemia.
• Easy bruising: With minor trauma or even without any injury.
• Neurological symptoms: Headaches, confusion, seizures, or strokes, due to clots affecting the brain.
• Fever: Often accompanies the disorder.
• Kidney dysfunction: Symptoms may include dark urine, decreased urine output, or swelling (due to kidney damage from clotting).
• Jaundice: Yellowing of the skin or eyes, due to the breakdown of red blood cells.
• Chest pain: If clots affect the heart.

Diagnosis

To diagnose TTP, doctors will perform a series of tests, including:

1. Blood tests:
   • Platelet count: A low platelet count is a key feature of TTP.
   • Lactate dehydrogenase (LDH): Elevated levels can indicate cell damage or destruction, often associated with TTP.
   • ADAMTS13 activity test: A blood test to measure the activity of the ADAMTS13 enzyme. A low level suggests TTP.
   • Haptoglobin: A low level may suggest hemolysis (destruction of red blood cells), a common feature of TTP.
2. Coagulation studies: Tests like PT (prothrombin time) and aPTT (activated partial thromboplastin time) are usually normal in TTP, which helps differentiate it from other clotting disorders.
3. Microscopic examination: Blood smears may show schistocytes, fragmented red blood cells, which are indicative of microangiopathic hemolytic anemia, a feature of TTP.

Treatment

TTP is a medical emergency and requires prompt treatment. The main goals of treatment are to stop the abnormal clotting, prevent organ damage, and address the underlying cause.

1. Plasma exchange (plasmapheresis): This is the primary treatment for acquired TTP. The procedure involves removing the patient's plasma, which contains the harmful antibodies attacking ADAMTS13, and replacing it with donor plasma. This helps restore ADAMTS13 activity and prevents further clotting.
2. Immunosuppressive medications: In addition to plasmapheresis, corticosteroids (e.g., prednisone) or other immunosuppressive drugs (such as rituximab) may be used to help control the immune system's response.
3. Platelet transfusions: These are generally avoided in TTP, as they can worsen clotting. However, in rare cases, platelet transfusions may be used if there is significant bleeding.
4. Supportive care: This may include dialysis for kidney failure, blood transfusions for anemia, and medications to manage other complications.

Prognosis

Without treatment, TTP can lead to severe complications, including organ failure (especially of the kidneys, heart, or brain), and can be fatal. However, with early and aggressive treatment, most people can recover. The prognosis depends on the severity of the disease, how quickly treatment is initiated, and whether there is any organ damage.

• Acquired TTP: The prognosis is generally better with plasma exchange, with many patients recovering fully or having good long-term outcomes.
• Inherited TTP: People with this form may experience more frequent relapses and require ongoing treatment, but with proper care, many lead relatively normal lives.

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