title: The effect of total hip/knee replacement surgery and prophylactic dabigatran on thrombin generation and coagulation parameters.
abstract: BACKGROUND
  Total hip/knee replacement surgery (THR/TKR respectively) is associated with an increased risk of venous thromboembolism. Dabigatran is recommended as a thromboprophylactic agent post orthopaedic surgery. The aim of this study was to assess the post-operative (Day-1 and Day-2) effect of prophylactic Dabigatran on: the thrombin generation (TG) assay; prothrombin fragment 1.2 (F1.2); thrombin-antithrombin complexes (TAT); D-dimer (D-D); and other coagulation parameters. METHODS AND SAMPLES: Nineteen patients (12 THR, 7 TKR) who received 110 mg dabigatran 4 hours post-operatively, then 220 mg the following day, were recruited. Blood was collected: pre-operatively (Pre-); peri-operatively (Peri-); 19 hours after 110 mg dabigatran (Day-1); and 17 hours after 220 mg dabigatran (Day-2). The TG assay was measured using the Calibrated Automated Thrombogram and a low concentration of tissue factor. Other coagulation parameters measured included activated partial thromboplastin time (APTT), thrombin-time (TT), ecarin-clotting time (ECT) and Hemoclot tests.
  
  
  RESULTS
  From Pre- to Peri-, ETP/peak-thrombin, F1.2, TAT and D-D increased significantly. From Peri- to Day-1 and Day-2: TAT reduced progressively; D-D increased; F1.2 did not change significantly; lag-time and time-to-peak prolonged; ETP/Peak-thrombin increased spuriously, due to Dabigatran interfering with the α-2 macroglobulin:thrombin complex in the TG assay. APTT, TT, ECT and Hemoclot increased progressively post-operatively; good correlations were seen between these tests.
  
  
  CONCLUSIONS
  The effect of dabigatran on the TG assay, showed a spurious increase in ETP and Peak-thrombin due to its interference with the TG assay. Dabigatran reduced TAT, but not F1.2, suggesting that thrombin was still being generated after surgery, but was blocked by Dabigatran.
authors.affiliation: Haemostasis Research Unit, University College London, London, United Kingdom. l.green@ucl.ac.uk
authors.forename: Laura
authors.initials: L
authors.lastname: Green
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Lawrie
authors.forename: Rahul
authors.initials: R
authors.lastname: Patel
authors.forename: Robert C M
authors.initials: RC
authors.lastname: Stephens
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Mackie
authors.forename: Andrew
authors.initials: A
authors.lastname: Chitolie
authors.forename: Fares S
authors.initials: FS
authors.lastname: Haddad
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Machin
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000627:therapeutic use*; D019644:Arthroplasty, Replacement, Hip / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000379:methods*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D000069604:Dabigatran; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013917:Thrombin / Q000096:biosynthesis*; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D015091:beta-Alanine; D013917:Thrombin; D000069604:Dabigatran