title: Latex D-dimer signal in in situ femoral vein thrombus in swine and effect of minidose exogenous tissue plasminogen activator bolus.
abstract: OBJECTIVE
  We created in situ femoral vein thrombi in swine to investigate the response of the latex d-dimer signal to acute in situ venous thrombosis, and to determine the minimum dose of exogenous bolus tissue plasminogen activator (t-PA) required to significantly elevate the d-dimer signal.
  
  
  METHODS
  We studied seven swine (20 to 22 kg) under pentobarbital anesthesia. A 6-cm segment of the proximal femoral vein was surgically exposed and briefly ligated. Thrombin, 250 U, was then injected into the isolated femoral vein segment to create an in situ clot. After clot formation was documented to be complete between the ligatures, they were then released. D-dimer levels were then measured every 15 min for 1 h before and 1 h after clot formation with ligatures released. Time-response curves to establish timing of peak t-PA effect were performed, and then escalating dose-response curves of d-dimer level to minidose t-PA were plotted.
  
  
  RESULTS
  After formation of the clot, the release of ligatures resulted in no change in d-dimer levels over 1 h (p = 0.62) in all swine. When a time-response curve to exogenous t-PA bolus in the presence of femoral clot was plotted, there was a maximal increase in d-dimer signal at 30 min after bolus t-PA administration. The subsequent dose-response curves for escalating fivefold boluses of minidose t-PA showed an increase in d-dimer signal at doses of 0.8 mg (p = 0.03) and 4 mg (p = 0.003).
  
  
  CONCLUSIONS
  We conclude the following: (1) in situ femoral vein clot formation does not elevate d-dimer signal for 1 h after ligature release; (2) minidose t-PA boluses of 0.8 mg and 4 mg significantly elevated the latex d-dimer signal above baseline; and (3) there is a potential role of minidose t-PA in enhancing the d-dimer signal in in situ deep venous thrombosis.
authors.affiliation: Medical College of Georgia, Section of Cardiology, BBR 6515A, Department of Medicine, Augusta, GA 30912, USA. vrobinso@mail.mcg.edu
authors.forename: Vincent J B
authors.initials: VJ
authors.lastname: Robinson
authors.forename: Guillermo E
authors.initials: GE
authors.lastname: Pineda
authors.forename: Ali K
authors.initials: AK
authors.lastname: Salah
authors.forename: Walter L
authors.initials: WL
authors.lastname: Pipkin
authors.forename: James H
authors.initials: JH
authors.lastname: Corley
authors.forename: Mary H
authors.initials: MH
authors.lastname: Jonah
authors.forename: James R
authors.initials: JR
authors.lastname: Gossage
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D007841:Latex Fixation Tests; D013552:Swine; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D016896:Treatment Outcome; D020246:Venous Thrombosis / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D010959:Tissue Plasminogen Activator