## Diagnosis of Thrombotic Thrombocytopenic Purpura (TTP) **Key Point:** ADAMTS13 deficiency (<10% activity) is the pathophysiologic hallmark and most specific diagnostic test for TTP, distinguishing it from other thrombotic microangiopathies. ### Why ADAMTS13 Activity Assay is Correct ADAMTS13 is a von Willebrand factor (vWF)-cleaving protease. Severe deficiency (<10% activity) leads to accumulation of ultra-large vWF multimers, causing platelet microthrombi and the pentad of TTP: 1. Thrombocytopenia 2. Microangiopathic hemolytic anemia (MAHA) 3. Neurological symptoms 4. Renal dysfunction 5. Fever **High-Yield:** ADAMTS13 activity <10% has >95% specificity for TTP when combined with clinical features; this is the gold-standard confirmatory test. ### Differential Diagnosis: TTP vs. HUS vs. DIC | Feature | TTP | HUS | DIC | |---------|-----|-----|-----| | ADAMTS13 activity | <10% (severe deficiency) | Normal | Normal | | Renal involvement | Mild to moderate | Severe (oliguria) | Variable | | Neurological symptoms | Common | Rare | Uncommon | | Coagulation studies (PT/aPTT) | Normal | Normal | Prolonged | | Fibrinogen | Normal | Normal | Decreased | | Platelet count | Severe (<50,000) | Variable | Severe | **Clinical Pearl:** Do NOT wait for ADAMTS13 results to initiate plasma exchange—start immediately if TTP is suspected clinically. ADAMTS13 testing confirms diagnosis retrospectively and guides long-term management. ### Why Other Investigations Are Insufficient - **Prothrombin time and aPTT:** Normal in TTP (coagulation cascade is intact). Prolongation suggests DIC, not TTP. - **Direct antiglobulin test (Coombs test):** Positive in immune hemolytic anemia but does not differentiate TTP from other causes of MAHA; not specific for TTP. - **Peripheral blood smear for schistocytes:** Confirms MAHA but is non-specific; schistocytes are seen in TTP, HUS, DIC, and malignant hypertension.
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