title: Thrombolytic therapy and proteolysis of factor V.
abstract: OBJECTIVE
  We sought to determine the extent of Factor V proteolysis during thrombolytic therapy.
  
  
  BACKGROUND
  Thrombin- or Factor Xa-activated Factor V is an essential cofactor in the prothrombinase complex. In purified systems, plasmin, the major product of thrombolytic therapy, is known to first activate then inactivate Factor V.
  
  
  METHODS
  We used quantitative gel electrophoresis and Western blotting to analyze the cleavages in plasma Factor V after thrombolytic therapy.
  
  
  RESULTS
  The addition of streptokinase to plasma resulted in the activation then inactivation of Factor V, confirming previous results using purified reagents. We also identified the Factor V fragments resulting from the action of thrombin and plasmin. After thrombolytic therapy, there was considerable Factor V cleavage. The cleavage patterns were consistent with the action of plasmin, with little evidence for the action of thrombin. In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries trial (n = 17), we observed an average 58% loss of intact Factor V at 6 h (range 1% to 91%). Samples from the Thrombolysis in Myocardial Infarction trial, Phase II (n = 12), collected on a shorter time scale, showed a loss of up to 99% at 50 min, with the loss of intact Factor V associated with the plasma concentration of plasminogen activator. Samples from patients with bleeding (n = 12) showed extensive Factor V cleavage.
  
  
  CONCLUSIONS
  Factor V cleavage in thrombolytic therapy is primarily plasmin mediated, rapid and often extensive. It is likely that transient increases, as well as longer term losses, of Factor V cofactor activity play a role in both ischemic and hemorrhagic events subsequent to thrombolytic therapy. The extensive loss of Factor V in some patients may affect the estimation of heparinization.
authors.affiliation: Department of Pathology, College of Medicine, University of Vermont, Burlington, USA. rtracy@salus.uvm.edu
authors.forename: R P
authors.initials: RP
authors.lastname: Tracy
authors.forename: D Z
authors.initials: DZ
authors.lastname: Rubin
authors.forename: K G
authors.initials: KG
authors.lastname: Mann
authors.forename: E G
authors.initials: EG
authors.lastname: Bovill
authors.forename: M
authors.initials: M
authors.lastname: Rand
authors.forename: D
authors.initials: D
authors.lastname: Geffken
authors.forename: P B
authors.initials: PB
authors.lastname: Tracy
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D015153:Blotting, Western; D005165:Factor V / Q000187:drug effects* / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D013300:Streptokinase / Q000494:pharmacology*; D013917:Thrombin / Q000378:metabolism; D015912:Thrombolytic Therapy
chemical_list: D005165:Factor V; D013300:Streptokinase; D013917:Thrombin; D005341:Fibrinolysin