Life-threatening thrombotic microangiopathy caused by severe ADAMTS13 deficiency (usually autoimmune), leading to ultra-large vWF multimers and platelet-rich microthrombi; results in microangiopathic hemolysis and organ ischemia.
Historically >90% fatal if untreated, but now highly survivable with prompt therapy. It's a hematologic emergency—timely plasma exchange is life-saving. Frequently appears on exams due to its classic pentad and the importance of urgent treatment.
Typically an adult (20–50s, often female) with acute or subacute onset of neurologic symptoms (confusion, seizures, stroke-like deficits) along with signs of anemia (fatigue, pallor) and thrombocytopenia (petechiae, bruising).
Fever and renal impairment can occur (the classic "FAT RN" pentad: Fever, Anemia [MAHA], Thrombocytopenia, Renal failure, Neurologic deficits), but the full pentad is present in only ~20–30% of cases.
Usually idiopathic (immune-mediated ADAMTS13 inhibitor). Some cases are drug-induced (e.g., ticlopidine, clopidogrel, quinine, gemcitabine) or associated with pregnancy, HIV, or malignancy.
Suspect TTP when you see thrombocytopenia + MAHA (microangiopathic hemolytic anemia: schistocytes on smear, ↑LDH, ↑indirect bilirubin, ↓haptoglobin) with normal coagulation tests (distinguishes from DIC).
Do not wait for ADAMTS13 assay results – if TTP is suspected, initiate plasma exchange immediately (draw sample for ADAMTS13 first, but treat based on clinical picture). Early plasma exchange removes autoantibodies and replenishes ADAMTS13, halting microthrombosis.
Differentiate from look-alikes: HUS (often child post-E. coli diarrhea, more renal failure, minimal neuro signs) and ITP (isolated platelets↓, no hemolysis or schistocytes). If in doubt, treat for TTP first, as delaying therapy can be fatal.
Normal PT/PTT in TTP: clotting factors are not consumed (helps distinguish TTP/HUS from DIC).
Do NOT delay plasma exchange – untreated TTP has ~90% mortality; start treatment on suspicion (each hour counts).
Avoid platelet transfusions in active TTP (unless life-threatening hemorrhage) – infusing platelets can worsen microthrombi formation.
Thrombocytopenia + hemolytic anemia (schistocytes, ↑LDH) → suspect TTP (especially if neuro or renal signs, and no DIC).
Emergent workup: draw labs (CBC, smear, hemolysis labs, BUN/Cr, PT/PTT, ADAMTS13 level) but do NOT wait for results to start therapy.
Begin plasmapheresis (plasma exchange) immediately and administer high-dose steroids. If acquired TTP, also give caplacizumab as adjunct.
Monitor daily platelet count and LDH. If inadequate response, escalate therapy (e.g., add rituximab). Continue plasma exchange until platelets normalize and hemolysis resolves.
Confused patient with petechiae, schistocytes on smear, ↑LDH, and normal coagulation studies → TTP (requires emergent plasma exchange).
Anemia with fragmented RBCs, thrombocytopenia, and slight creatinine elevation in an adult with no recent infection → suspect TTP (even if no fever or obvious neuro symptoms, treat immediately).
Case 1
A 32‑year‑old woman presents with confusion, headache, and easy bruising over one week.
Case 2
A 50‑year‑old man is found to have anemia and thrombocytopenia (with scattered petechiae) during an evaluation for fatigue. He has no fever or history of recent infection.
Peripheral blood smear with multiple schistocytes (fragmented red blood cells).
