Snapshot A 24-year-old woman presents to the ED with acute-onset fatigue, fever, and blurry vision. On chart review, it is revealed that she was recently diagnosed with AIDS and was on multiple anti-retroviral medications. On physical exam, her skin is mildly jaundiced. She has multiple purpura over her extremities. Her peripheral smear reveals with schistocytes. Introduction Thrombotic microangiopathy characterized by a pentad microangiopathic hemolytic anemia acute renal failure thrombocytopenia fever neurologic abnormalities Similar to HUS but with fever and neurologic symptoms Epidemiology female > male most commonly in young adults African-Americans Pathogenesis deficiency or inhibition of metalloproteinase ADAMTS13 most commonly disabled by an autoantibody ADAMTS13 degrades vWF multimers deficiency → large vWF multimers → increased platelet adhesion → platelet thrombosis damages brain and kidneys important underlying risk factor, but requires a secondary trigger triggers drugs (quinine, ticlopidine, clopidogrel, and cyclosporine) SLE infections AIDS malignancies Presentation Symptoms (recall pentad) thrombocytopenia easy bleeding epistaxis neurological symptoms confusion seizures headaches nonspecific symptoms weakness vomiting nausea thrombosis renal dysfunction (less so than HUS) Physical exam fever pallor (from anemia) purpura/petechiae jaundice (from hemolysis) splenomegaly (unlike ITP) Evaluation Complete blood count anemia thrombocytopenia Peripheral blood smear schistocytes (helmet cells) Serum ↑ LDH ↑ creatinine negative Coomb’s Normal PT/PTT ↑ bleeding time Differential TTP HUS DIC Other causes of microangiopathic hemolytic anemia: prosthetic valve hemolysis metastatic adenocarcinoma malignant HTN vasculitis Characteristics DIC ITP TTP HUS Fever No No Yes Yes/No Splenomegaly No No Yes Yes Platelets Low Low Low Low Bleeding time ↑ ↑ ↑ ↑ PT ↑ - - - PTT ↑ - - - Shistocytes Yes No Yes Yes Trauma Yes No No No Treatment` First-line therapy plasma exchange transfusion with fresh frozen plasma Anecdotal evidence steroids splenetcomy if recurrent Platelet transfusion contraindicated platelet transfusion will worsen disease by feeding the platelet consumption Prognosis, Prevention, and Complications Prognosis remission with plasma exchange in majority of patients mortality rate 13-15% Complications permanent neurologic sequelae chronic kidney disease especially with quinine-induced TTP