title: The low molecular weight heparin Enoxaparin inhibits the consumption of factor VII and prothrombin activation in vivo associated with elective knee replacement surgery.
abstract: Patients over 40 years of age who undergo elective orthopaedic surgery have a relatively high risk for developing post-surgical deep vein thrombosis (DVT). Prophylactic use of heparin or low molecular weight heparins can reduce the incidence of post-operative DVT by up to 80%. It is not known whether prophylaxis is achieved by inhibition of prothrombin activation or catalysis of thrombin inhibition in vivo. We determined the changes in concentrations of factor VII zymogen and thrombin-antithrombin III (the latter as an index of prothrombin activation) in the plasmas of 129 patients randomized to receive two daily subcutaneous injections of placebo or 30 mg of Enoxaparin after elective knee surgery. Enoxaparin reduced the frequency of post-surgical DVT by 70%. The concentration of factor VII zymogen had decreased by approximately 50% within 24 h after the knee surgery, followed by a gradual increase to near presurgical values. Additionally, post-Enoxaparin plasmas had statistically significant higher concentrations of factor VII zymogen than post-placebo plasmas. Post-Enoxaparin plasmas had significantly lower concentrations of endogenous thrombin-antithrombin III than comparable post-placebo plasmas. Finally, post-Enoxaparin plasmas inactivated exogenous factor Xa and thrombin more effectively than comparable post-placebo plasmas. As Enoxaparin moderated the generation of endogenous thrombin-antithrombin III after elective knee surgery, inhibition of prothrombin activation in vivo by Enoxaparin may be important for its prophylactic antithrombotic effect.
authors.affiliation: Canadian Red Cross Society, Blood Services, Hamilton, Ontario.
authors.forename: F A
authors.initials: FA
authors.lastname: Ofosu
authors.forename: J
authors.initials: J
authors.lastname: Leclerc
authors.forename: F
authors.initials: F
authors.lastname: Delorme
authors.forename: S
authors.initials: S
authors.lastname: Craven
authors.forename: S
authors.initials: S
authors.lastname: Shafai
authors.forename: L
authors.initials: L
authors.lastname: Frewin
authors.forename: M A
authors.initials: MA
authors.lastname: Blajchman
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D003864:Depression, Chemical; D004792:Enzyme Precursors / Q000097:blood / Q000378:metabolism; D005167:Factor VII / Q000378:metabolism; D015951:Factor Xa / Q000378:metabolism; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use*; D006801:Humans; D007720:Knee Prosthesis; D010447:Peptide Hydrolases / Q000378:metabolism; D011183:Postoperative Complications / Q000517:prevention & control*; D011498:Protein Precursors; D011516:Prothrombin / Q000378:metabolism; D013924:Thrombophlebitis / Q000517:prevention & control*
chemical_list: D004792:Enzyme Precursors; D006495:Heparin, Low-Molecular-Weight; D011498:Protein Precursors; C046193:antithrombin III-protease complex; C071874:prepro-factor VII; D000990:Antithrombin III; D005167:Factor VII; D011516:Prothrombin; D010447:Peptide Hydrolases; D015951:Factor Xa