title: Increased heparanase level and procoagulant activity in orthopedic surgery patients receiving prophylactic dose of enoxaparin.
abstract: BACKGROUND
  Orthopedic hip and knee surgeries are followed by a hypercoagulable state. Heparanase is implicated in inflammation, coagulation activation and angiogenesis. Recently, heparanase was shown to directly interact with tissue factor (TF) and to enhance the generation of factor Xa (Nadir et al., Haematologica, 2010). In addition, an assay assessing heparanase procoagulant activity has been lately developed (Nadir et al., Thromb Res, 2011). In the present study heparanase level and procoagulant activity in patients undergoing orthopedic surgery were assessed.
  
  
  METHODS
  The study group included 50 orthopedic patients. 31 patients underwent hip surgery and 19 had knee operation. 15 individuals suffered from traumatic hip fractures and 35 had osteoarthrosis of hip or knee joints. All patients received prophylactic dose of enoxaparin starting 6-8 hours post operation and lasting for 5 weeks. Plasma samples were drawn preoperatively and at 1 hour, 1 week and 1 month post operation. Samples were tested for heparanase levels by ELISA and TF/heparanase complex activity, TF activity, heparanase procoagulant activity, factor Xa and thrombin levels using chromogenic substrates.
  
  
  RESULTS
  Heparanase levels were significantly higher 1 hour and 1 week post operatively compared to preoperative levels (p<0.05, p<0.005, respectively). The most dramatic changes were observed in heparanase procoagulant activity reaching a 2 fold increase 1 week postoperatively and 1.7 fold increase 1month after surgery (p<0.0001, p<0.0001, respectively). Levels of factor Xa and thrombin did not significantly change.
  
  
  CONCLUSIONS
  Heparanase is involved in coagulation activation of orthopedic surgery patients. Heparanase procoagulant activity is highest 1 week postoperatively and remains high 1month after operation. Considering extending prophylactic anticoagulant therapy or evaluating heparanase procoagulant activity may potentially prevent late thrombotic events.
authors.affiliation: Department of Orthopedic B, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Peled
authors.forename: Alexey
authors.initials: A
authors.lastname: Rovitsky
authors.forename: Elena
authors.initials: E
authors.lastname: Axelman
authors.forename: Doron
authors.initials: D
authors.lastname: Norman
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenner
authors.forename: Yona
authors.initials: Y
authors.lastname: Nadir
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D017984:Enoxaparin / Q000627:therapeutic use*; D015951:Factor Xa / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000097:blood*; D006615:Hip / Q000601:surgery; D006801:Humans; D007717:Knee / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000009:adverse effects*; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism; D013927:Thrombosis / Q000201:enzymology / Q000517:prevention & control*; D000099175:Heparanase
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D015951:Factor Xa; D005966:Glucuronidase; D013917:Thrombin; D013925:Thromboplastin; D000099175:Heparanase