title: Heparanase procoagulant activity as a predictor of wound necrosis following diabetic foot amputation.
abstract: BACKGROUND
  Trans-metatarsal operation to diabetic foot necrosis is a common procedure although only half of the patients do not need a second amputation due to surgery wound ischemia. No current tools are available for early prediction of surgery success and the clinical decision for a second operation may take weeks. Heparanase protein is involved in inflammation, angiogenesis and coagulation activation. The aim of the study was to evaluate heparanase level and procoagulant activity as an early predictor for success or failure of diabetic foot trans-metatarsal surgery.
  
  
  METHODS
  The study group included 40 patients with diabetic foot necrosis requiring trans-metatarsal surgical intervention. Eighteen patients designated as necrotic group, developed post-surgery necrosis at the surgery wound within the first month, requiring a second more proximal amputation. Skin biopsies from the proximal surgery edge were stained for heparanase, tissue factor (TF), TF pathway inhibitor (TFPI) and by hematoxylin and eosin. Plasma samples were drawn pre-surgery and at 1h, 1week and 1month post-surgery. Samples were tested for heparanase levels by ELISA and TF+heparanase activity, TF activity and heparanase procoagulant activity.
  
  
  RESULTS
  Skin biopsy staining did not predict subsequent necrosis. In the non-necrotic group a significant rise in TF+heparanase activity, heparanase activity and heparanase levels were observed 1h and 1week post-surgery. The most significant increase was in heparanase procoagulant activity at the time point of 1h post-surgery (P<0.0001). Pre-surgery TF activity was significantly lower in the non-necrotic group compared to the necrotic group (P<0.05).
  
  
  CONCLUSIONS
  Measuring heparanase procoagulant activity pre-surgery and 1h post-surgery could potentially serve as an early tool to predict the procedure success. The present results broaden our understanding regarding early involvement of heparanase in the wound healing process.
authors.affiliation: Division of Orthopedic, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Eli
authors.initials: E
authors.lastname: Peled
authors.affiliation: Division of Orthopedic, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Melamed
authors.affiliation: Division of Orthopedic, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Tali Banker
authors.initials: TB
authors.lastname: Portal
authors.affiliation: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Elena
authors.initials: E
authors.lastname: Axelman
authors.affiliation: Division of Orthopedic, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Norman
authors.affiliation: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Brenner
authors.affiliation: Thrombosis and Hemostasis Unit, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion, Haifa, Israel. Electronic address: ynadir@netvision.net.il.
authors.forename: Yona
authors.initials: Y
authors.lastname: Nadir
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D001777:Blood Coagulation; D017719:Diabetic Foot / Q000097:blood* / Q000150:complications / Q000473:pathology / Q000601:surgery*; D005260:Female; D005966:Glucuronidase / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000473:pathology; D012867:Skin / Q000473:pathology*; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism; D014945:Wound Healing; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D013925:Thromboplastin; D000099175:Heparanase
keywords: Amputation; Diabetic foot; Heparanase; Necrosis