title: Low thrombin generation during major orthopaedic surgery fails to predict the bleeding risk in inhibitor patients treated with bypassing agents.
abstract: BACKGROUND
  In the presence of high-titre inhibitors, haemostatic bypassing agents are used to control bleeding and perform surgery. In this setting, no specific laboratory test is yet available to guide drug choice, monitor treatment efficacy and predict the risk of bleeding.
  
  
  OBJECTIVE
  The aims of this study, carried out in patients candidate to orthopaedic surgery, were to assess the dose-dependent increase in thrombin generation (TG) after infusion of bypassing agents and to evaluate whether or not a correlation existed between the haemostatic efficacy of bypassing therapies and perioperative TG values.
  
  
  RESULTS
  TG was measured in 16 inhibitor patients, 10 of whom underwent 11 major orthopaedic procedures. In the non-bleeding state, TG significantly improved 30 min after whichever dose (P < 0.01), with no dose-response relationship when values obtained after different rFVIIa doses were compared. TG significantly improved 30 min after the preoperative bolus (P < 0.05), while during the postoperative period TG values measured before and after dosing did not differ. Moreover, postoperative TG values were similar or even more impaired (P ≤ 0.05) than those measured before preoperative dosing. No difference was found by comparing procedures with and without bleeding complications and yet no bleeding occurred in spite of persistently low TG values in one-third of procedures.
  
  
  CONCLUSIONS
  This study fails to support a definite role for the TG assay as a reliable laboratory tool to monitor the haemostatic efficacy of bypassing therapies and as a predictor of the risk of bleeding in inhibitor patients using these agents during orthopaedic surgery.
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M E
authors.initials: ME
authors.lastname: Mancuso
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Chantarangkul
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Fasulo
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Padovan
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Scalambrino
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.|Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Tripodi
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Santagostino
mesh_terms: D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D001779:Blood Coagulation Factors / Q000627:therapeutic use*; D003029:Coagulants / Q000627:therapeutic use*; D015942:Factor VIIa / Q000627:therapeutic use*; D006467:Hemophilia A / Q000188:drug therapy* / Q000473:pathology; D006470:Hemorrhage / Q000517:prevention & control; D006801:Humans; D008297:Male; D011300:Preoperative Care; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D013514:Surgical Procedures, Operative; D013917:Thrombin / Q000032:analysis*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D001779:Blood Coagulation Factors; D003029:Coagulants; D011994:Recombinant Proteins; C025667:prothrombin complex concentrates; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin
keywords: Thrombin generation; endogenous thrombin potential; haemophilia; inhibitors; orthopaedic surgery