title: Mechanism of catheter thrombosis: comparison of the antithrombotic activities of fondaparinux, enoxaparin, and heparin in vitro and in vivo.
abstract: In patients undergoing percutaneous coronary intervention, catheter thrombosis is more frequent with fondaparinux than heparin. This study was undertaken to identify the responsible mechanism and to develop strategies for its prevention. Percutaneous coronary intervention catheter segments shortened plasma clotting times from 971 ± 92 to 352 ± 22 seconds. This activity is factor XII (fXII) dependent because it was attenuated with corn trypsin inhibitor and was abolished in fXII-deficient plasma. Heparin and enoxaparin blocked catheter-induced clotting at 0.5 and 2 anti-Xa U/mL, respectively, whereas fondaparinux had no effect. Addition of fondaparinux to bivalirudin or low-dose heparin attenuated catheter-induced clotting more than either agent alone. In a rabbit model of catheter thrombosis, a 70 anti-Xa U/kg intravenous bolus of heparin or enoxaparin prolonged the time to catheter occlusion by 4.6- and 2.5-fold, respectively, compared with saline, whereas the same dose of fondaparinux had no effect. Although 15 anti-Xa U/kg heparin had no effect on its own, when given in conjunction with 70 anti-Xa U/kg fondaparinux, the time to catheter occlusion was prolonged 2.9-fold. These findings indicate that (1) catheters are prothrombotic because they trigger fXII activation, and (2) fondaparinux does not prevent catheter-induced clotting unless supplemented with low-dose heparin or bivalirudin.
authors.affiliation: School of Biomedical Engineering, Department of Medicine, McMaster University and the Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Yau
authors.forename: Alan R
authors.initials: AR
authors.lastname: Stafford
authors.forename: Peng
authors.initials: P
authors.lastname: Liao
authors.forename: James C
authors.initials: JC
authors.lastname: Fredenburgh
authors.forename: Robin
authors.initials: R
authors.lastname: Roberts
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects; D001780:Blood Coagulation Tests; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D057785:Catheters / Q000009:adverse effects; D004195:Disease Models, Animal; D004357:Drug Synergism; D017984:Enoxaparin / Q000494:pharmacology*; D005174:Factor XII / Q000378:metabolism; D000077425:Fondaparinux; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011134:Polysaccharides / Q000494:pharmacology*; D011817:Rabbits; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D011134:Polysaccharides; D005174:Factor XII; D006493:Heparin; D000077425:Fondaparinux