title: Complement activation, inflammation and relative ADAMTS13 deficiency in secondary thrombotic microangiopathies.
abstract: The secondary forms of hemolytic uremic syndrome/thrombotic thrombocytopenic purpura (secondary TMA) emerge as complications of coexisting diseases.
  
  
  
  We hypothesized that secondary TMA could be characterized by the presence of relative ADAMTS13 deficiency and complement activation, and this relationship may have a prognostic value for outcome.
  
  
  
  Fifty-three patients with thrombotic microangiopathy (TMA) and coexisting disease (such as malignancies, sepsis, heart surgery with extracorporeal circulation, solid organ transplantation, systemic autoimmune disorders), 41 patient controls, and 34 healthy controls were enrolled in our case-control study with 30days follow-up. Complement profile (from serum) and activation products, von Willebrand factor (VWF, from EDTA plasma), and ADAMTS13 activity were determined.
  
  
  
  ADAMTS13 activity was reduced, while VWF level was elevated in secondary TMA patients. The activity of the classical, lectin and alternative pathways, as well as the levels of C3, C4, and Factor H were significantly lower in secondary TMA patients, and were accompanied by high activation product levels (C3a and sC5b-9). Factor H concentration correlated to relative ADAMTS13 deficiency (i.e. VWF/ADAMTS13 ratio (r=-0.368, p=0.019)). 28/53 patients (53%) died during the follow-up period. Increased sC5b-9, C3a, and C reactive protein levels were all associated with a poor patient outcome.
  
  
  
  Our results indicate that the secondary TMA syndrome and its poor outcome is characterized by relative ADAMTS13 deficiency, inflammation, and complement activation with consumption via the classical and alternative pathways. It is yet to be determined whether complement inhibition could be a possible therapeutic option for patients with secondary TMA.
authors: 3rd Department of Internal Medicine, Research Laboratory and Füst György Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary.
authors: Péter
authors: P
authors: Farkas
authors: 3rd Department of Internal Medicine, Research Laboratory and Füst György Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary.
authors: Dorottya
authors: D
authors: Csuka
authors: 3rd Department of Internal Medicine, Research Laboratory and Füst György Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary.
authors: Bálint
authors: B
authors: Mikes
authors: 3rd Department of Internal Medicine, Research Laboratory and Füst György Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary.
authors: György
authors: G
authors: Sinkovits
authors: Department of Hematology and Stem Cell Transplantation, St István and St László Hospital of Budapest, Budapest, Hungary.
authors: Marienn
authors: M
authors: Réti
authors: Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Hungary.
authors: Endre
authors: E
authors: Németh
authors: Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Hungary.
authors: Kristóf
authors: K
authors: Rácz
authors: Department of Anaesthesiology and Intensive Therapy, Semmelweis University, Hungary.
authors: Krisztina
authors: K
authors: Madách
authors: GottsegenGyörgy National Cardiology Institute, Budapest, Hungary.
authors: Mihály
authors: M
authors: Gergely
authors: 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors: Judit
authors: J
authors: Demeter
authors: 3rd Department of Internal Medicine, Research Laboratory and Füst György Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary. Electronic address: prohoz@kut.sote.hu.
authors: Zoltán
authors: Z
authors: Prohászka
mesh_terms: D000071120:ADAMTS13 Protein / Q000172:deficiency*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D003167:Complement Activation / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D057049:Thrombotic Microangiopathies / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000401:mortality; D055815:Young Adult
chemical_list: D015415:Biomarkers; D003165:Complement System Proteins; D000071120:ADAMTS13 Protein
keywords: Complement activation; Factor H; In-hospital mortality; Relative ADAMTS13 deficiency; Secondary thrombotic microangiopathy