title: Prothrombin fragment 1+2 in urine as an indicator of sustained coagulation activation after total hip arthroplasty.
abstract: OBJECTIVE
  Prothrombin fragment 1+2 measured in spot urine (uF1+2) is an indicator of thrombin generation. We examined whether measured levels of uF1+2 can be used to differentiate between patients who do and do not acquire sustained coagulation activation after total hip arthroplasty (THA).
  
  
  METHODS
  We performed two separate studies in patients undergoing THA. Study 1 was a prospective pilot study aiming to roughly estimate the extent of pre- and postoperative fluctuations in the uF1+2 concentration. Study 2 was a larger prospective cohort study aiming to verify the findings of Study 1 and to examine the association between the uF1+2 concentrations and risk of vascular thrombotic complications (VTC) or death. Finally, we sought to define a cut-off concentration value that could be used to identify patients with a sustained uF1+2 elevation after the first postoperative week. The urine samples were analysed by ELISA. In both studies thromboprophylaxis was used for at least 7 days after the operation.
  
  
  RESULTS
  The operative trauma resulted in elevation of the uF1+2 level in all patients compared with the preoperative level and levels in the healthy volunteers. Ten out of 113 patients (8.8%) in the second study suffered VTC or death, assumed to be caused by a coagulation problem. Analysis of variance revealed the following statistically significant associations: pre- vs. postoperative log uF1+2 levels (P<0.0001), log uF1+2 levels comparing patients with and without events (P=0.004); and the individual log uF1+2 levels (P<0.0001). A cut-off value of uF1+2 concentration between 0.3 and 0.5 nmol/l had a sensitivity and a negative predictive value between100% and 90%, and specificity between 45% and 63% and overall accuracy between 50% and 65%. This value was obtained by the analysis of a receiver operating characteristic curve with the purpose of identifying patients with sustained coagulation activation on day 5 after operation.
  
  
  CONCLUSIONS
  Our studies suggest that measured levels of uF1+2 can be potentially used to assess the individual risk of VTC after THA and to test for non-invasive detection of sustained coagulation activation.
authors.affiliation: Department of Orthopaedics, Section of Traumatology, Arhus University Hospital, Arhus. lborr@as.aaa.dk
authors.forename: Lars C
authors.initials: LC
authors.lastname: Borris
authors.forename: Morten
authors.initials: M
authors.lastname: Breindahl
authors.forename: Camilla
authors.initials: C
authors.lastname: Ryge
authors.forename: Helle M
authors.initials: HM
authors.lastname: Sommer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lassen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D015415:Biomarkers / Q000652:urine; D001778:Blood Coagulation Disorders / Q000097:blood / Q000209:etiology* / Q000652:urine*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000652:urine*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000097:blood / Q000209:etiology* / Q000652:urine*; D011446:Prospective Studies; D011516:Prothrombin / Q000652:urine*; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000652:urine
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D011516:Prothrombin