TTP (Thrombotic Thrombocytopenic Purpura)

I. 定义

Thrombotic Thrombocytopenic Purpura (TTP) is a rare and life - threatening thrombotic microangiopathy. It is characterized by a combination of thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (red blood cells are damaged as they pass through narrowed blood vessels), neurological abnormalities, renal impairment, and fever.

II. Pathogenesis

1. ADAMTS13 deficiency
   • A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) is an enzyme that cleaves von Willebrand factor (vWF). In TTP, there is a deficiency of ADAMTS13, either due to inherited mutations or the presence of autoantibodies against the enzyme.
   • Uncleaved vWF multimers accumulate in the blood. These large vWF multimers can cause platelet aggregation and the formation of microthrombi in small blood vessels throughout the body.
2. Endothelial cell damage
   • The presence of microthrombi also leads to endothelial cell damage. This further disrupts normal blood flow and contributes to the ongoing thrombotic process.
   • The damaged endothelium releases various cytokines and chemokines that attract more platelets and white blood cells, exacerbating the inflammatory and thrombotic response.

III. Clinical Features

1. Bruising and bleeding
   • Thrombocytopenia results in easy bruising, petechiae (small red or purple spots on the skin), and mucosal bleeding such as nosebleeds, gum bleeding, and gastrointestinal bleeding.
2. Anemia
   • Microangiopathic hemolytic anemia leads to symptoms of anemia, including fatigue, weakness, shortness of breath, and pallor. The fragmented red blood cells (schistocytes) can be seen on blood smear examination.
3. Neurological symptoms
   • Patients may experience a variety of neurological manifestations, such as headache, confusion, altered mental status, seizures, and stroke - like episodes. These are due to the formation of microthrombi in the small blood vessels of the brain.
4. Renal impairment
   • Kidney function can be affected, leading to proteinuria, hematuria, and decreased creatinine clearance. In severe cases, acute kidney injury may occur.
5. Fever
   • Low - grade fever is often present, which may be related to the underlying inflammatory process associated with TTP.

IV. Diagnosis

1. Clinical criteria
   • The presence of thrombocytopenia, microangiopathic hemolytic anemia, and at least one of the other major clinical features (neurological, renal, or fever) is highly suggestive of TTP.
2. Laboratory tests
   • Blood tests are crucial. Low platelet count, elevated lactate dehydrogenase (LDH) due to hemolysis, decreased haptoglobin (a protein that binds free hemoglobin), and the presence of schistocytes on blood smear are characteristic findings.
   • Measurement of ADAMTS13 activity is also important. Levels less than 10% of normal are highly indicative of TTP, especially in the presence of inhibitory autoantibodies against ADAMTS13.

V. Treatment

1. Plasma exchange
   • Plasma exchange is the mainstay of treatment. It involves removing the patient's plasma and replacing it with fresh frozen plasma. This helps to replenish ADAMTS13 and remove the large vWF multimers and autoantibodies.
2. Glucocorticoids
   • Corticosteroids such as prednisone may be used in combination with plasma exchange. They can help to suppress the immune response and reduce inflammation associated with TTP.
3. Other immunosuppressive agents
   • In some cases, other immunosuppressive drugs like rituximab may be considered, especially if the patient does not respond well to plasma exchange and glucocorticoids.