title: Changes in fibrinolysis and severity of organ failure in sepsis: a prospective observational study using point-of-care test--ROTEM.
abstract: OBJECTIVE
  We hypothesized that the thromboelastometry (ROTEM; Pentapharm GmbH, Munich, Germany) fibrinolysis parameter "maximum lysis" (ML) would have an independent inverse association with the severity of organ failure in sepsis.
  
  
  METHODS
  Selected adult patients with sepsis (n = 77) were recruited within 24 hours of antibiotic commencement. Patients with Sequential Organ Failure Assessment score higher than 1 (n = 57) were followed for 72 hours. Prothrombin fragments 1 + 2, plasminogen activator inhibitor-1 (aPAI-1), ROTEM, and routine coagulation tests were measured daily along with Sequential Organ Failure Assessment scores.
  
  
  RESULTS
  The activity of functional aPAI-1 increased with increasing severity of organ failure (P = .01) and was higher as compared with healthy controls (95% confidence interval, -65.4 to -29.9; P < .001). There was a decreasing trend in ML with increased organ failure (P = .001); however, there was no trend in d-dimer. Among all tests, only the lower ML (ß = -0.38, P < .001) and higher international normalized ratio (INR; ß = 0.32, P = .002) values significantly contributed to greater severity of organ failure (R(2) = 0.35, F2,73 = 19.29, P < .001). Despite an increase in INR, the prothrombin fragment remained unchanged (P = .89). Strong correlations were observed between early (24 hours) increase in fibrinolysis and recovery of organ failures for 48 hours (ML: r = 0.679, P = .001; aPAI-1: r = 0.694, P < .001).
  
  
  CONCLUSIONS
  Lower ML and higher INR values predicted greater severity of organ failure at presentation. Further studies are required, as ROTEM could aid selection of patients and guide interventions aimed at fibrinolysis in severe sepsis.
authors.affiliation: Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia. Electronic address: shiveshprakash@gmail.com.
authors.forename: Shivesh
authors.initials: S
authors.lastname: Prakash
authors.affiliation: Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
authors.forename: Santosh
authors.initials: S
authors.lastname: Verghese
authors.affiliation: Transfusion Service, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
authors.forename: David
authors.initials: D
authors.lastname: Roxby
authors.affiliation: Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
authors.forename: Dani
authors.initials: D
authors.lastname: Dixon
authors.affiliation: Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
authors.forename: Shailesh
authors.initials: S
authors.lastname: Bihari
authors.affiliation: Department of Critical Care Medicine, Flinders Medical Centre, Bedford Park, SA 5042, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bersten
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D001780:Blood Coagulation Tests; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D005858:Germany; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D019095:Point-of-Care Systems; D011446:Prospective Studies; D011516:Prothrombin; D018805:Sepsis / Q000097:blood; D013916:Thrombelastography
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D011516:Prothrombin
keywords: Coagulation; Fibrinolysis; Plasminogen activator inhibitor-1; ROTEM; Sepsis; Thromboelastometry