title: Value of ADAMTS13 activity and inhibitor in the postmortem diagnosis of thrombotic thrombocytopenic purpura.
abstract: OBJECTIVE
  Thrombotic thrombocytopenic purpura (TTP) is a clinical diagnosis that can be difficult to establish in severely ill patients. We report a case of fulminant TTP in a woman who died before receiving plasma exchange. An autopsy plasma sample was analyzed for ADAMTS13 activity and inhibitor for correlation with the diagnosis of TTP. Recognizing that hemolysis in postmortem blood samples could interfere with ADAMTS13 activity, plasma samples from four additional decedents not suspected of having TTP were analyzed and correlated with their autopsy results. The purpose of this study was to assess whether testing postmortem samples for ADAMTS13 is useful in the postmortem diagnosis of TTP.
  
  
  METHODS
  Plasma samples from the index case and four non-TTP decedents were analyzed for ADAMTS13 activity, ADAMTS13 inhibitor levels, and plasma free hemoglobin (PFH). Autopsy tissues were evaluated for evidence of platelet microthrombi in all five cases.
  
  
  RESULTS
  The ADAMTS13 activity level in the index patient was <4%, and the inhibitor level was 1.0 inhibitor unit. Microthrombi were prominent in the heart, kidneys, pancreas, and adrenal glands, consistent with the clinical diagnosis of TTP. ADAMTS13 activity levels in the four non-TTP decedents ranged from 4 to 82% (3/4 < or = 26%), and inhibitor was present in two of the four samples. Postmortem PFH levels in the four non-TTP decedents ranged from 64 to 3,917 mg/dL. No microthrombi were observed.
  
  
  CONCLUSIONS
  Low postmortem ADAMTS13 activity and evidence of inhibitor can occur in decedents without clinical or histologic evidence of TTP. Postmortem ADAMTS13 activity levels may not be valid in establishing a diagnosis of TTP, and high inhibitor levels in this setting may be related to elevated PFH. Caution must be used in the interpretation of ADAMTS13 testing in the presence of hemolysis.
authors.affiliation: Department of Pathology, University of California Davis Medical Center, Sacramento, California 95817, USA. denis.dwyre@ucdmc.ucdavis.edu
authors.forename: Denis M
authors.initials: DM
authors.lastname: Dwyre
authors.forename: Bryce
authors.initials: B
authors.lastname: Dursteler
authors.forename: Marcus
authors.initials: M
authors.lastname: Nashelsky
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Friedman
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Raife
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000368:Aged; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D010951:Plasma Exchange; D011480:Protease Inhibitors / Q000097:blood*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood* / Q000175:diagnosis* / Q000628:therapy
chemical_list: D011480:Protease Inhibitors; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human