TTP
Summary
Thrombotic Thrombocytopenic Purpura (TTP) is a thrombotic microangiopathy caused by deficiency or inhibition of ADAMTS13, leading to large vWF multimers that cause platelet microthrombi, hemolysis, and organ ischemia. It classically presents with a pentad: fever, microangiopathic hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic symptoms (though full pentad is rare). It's a medical emergency treated with plasma exchange, not platelet transfusion.
Detail
TTP results from severe deficiency (<10%) of ADAMTS13, a metalloprotease that normally cleaves ultra-large von Willebrand factor (vWF) multimers. This can be hereditary (Upshaw-Schulman syndrome) or, more commonly, acquired due to autoantibodies inhibiting ADAMTS13 activity. Without cleavage, ultra-large vWF multimers persist in circulation, promoting excessive platelet adhesion and aggregation, forming microthrombi in small vessels throughout the body. This leads to: (1) Microangiopathic hemolytic anemia (MAHA) - mechanical destruction of RBCs passing through platelet-fibrin thrombi, producing schistocytes on peripheral smear; (2) Thrombocytopenia from platelet consumption; (3) Organ ischemia, particularly affecting the brain (confusion, seizures, headache) and kidneys (though less severe than HUS), as well as potential cardiac and GI involvement; (4) Fever (less commonly seen now); (5) Renal failure. Unlike DIC, coagulation studies (PT, PTT, fibrinogen) are typically normal in TTP since the primary process is platelet-mediated, not a global coagulopathy. Diagnosis is confirmed by low ADAMTS13 activity level and presence of inhibitor antibodies in acquired cases. Treatment is urgent plasma exchange (plasmapheresis) to remove autoantibodies and ultra-large vWF multimers while replenishing ADAMTS13; corticosteroids and rituximab may be added for immune-mediated cases. Platelet transfusions are contraindicated as they can exacerbate microthrombus formation and worsen ischemic damage. TTP must be distinguished from Hemolytic Uremic Syndrome (HUS), which is typically caused by Shiga toxin (E. coli O157:H7) and predominantly causes renal failure in children, with normal ADAMTS13 levels.
Sources
- First Aid for the USMLE Step 1
- Pathoma - Fundamentals of Pathology
- Robbins and Cotran Pathologic Basis of Disease
- UpToDate - Thrombotic Thrombocytopenic Purpura
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