title: An antifibrinolytic effect associated with an anti-factor V antibody in a patient with severe thrombophilia.
abstract: OBJECTIVE
  The case of a patient with thrombotic manifestations and severe activated protein C resistance due to an anti-factor V antibody has recently been described. Since activated protein C (APC) is also profibrinolytic we wanted to determine whether the presence of antibodies interfering with the anticoagulant activity of APC also inhibits its profibrinolytic effect.
  
  
  METHODS
  Plasma clots were formed in the presence of tissue plasminogen activator, thrombin, phospholipids, Ca++, and various concentrations of APC, and the rate of lysis was monitored over time by the reduction in turbidity. Generation of endogenous thrombin and activation of thrombin activatable fibrinolysis inhibitor (TAFI) were also determined during fibrinolysis by clotting and spectrophotometric assays, respectively.
  
  
  RESULTS
  Addition of APC to the patient's plasma failed to stimulate fibrinolysis even at a concentration 4 times higher than that needed to produce the maximal effect in control plasma. Removal of IgG from the patient's plasma fully restored the fibrinolytic response to APC. Accordingly, addition of the patient's IgG to control plasma caused a concentration-dependent inhibition of APC-dependent fibrinolysis. The patient's IgG did not, however, inhibit the profibrinolytic effect of heparin. Determination of thrombin and activated TAFI generation during clot lysis showed that APC inhibited the generation of these enzymes by less than 20% in plasma supplemented with the patient's IgG as opposed to >80% in a control sample.
  
  
  CONCLUSIONS
  Our data suggest that the anti-factor V antibody inhibits fibrinolysis by antagonizing the anticoagulant effect of APC thereby favoring thrombin generation and TAFI activation. Impaired fibrinolysis may represent an additional mechanism contributing to thrombosis in patients with severe APC resistance phenotype.
authors.affiliation: Department of Biomedical Sciences, University of Bari, Italy. mario.colucci@dimo.uniba.it
authors.forename: Mario
authors.initials: M
authors.lastname: Colucci
authors.forename: Paolo
authors.initials: P
authors.lastname: Simioni
authors.forename: Donatella
authors.initials: D
authors.lastname: Piro
authors.forename: Paolo
authors.initials: P
authors.lastname: Prandoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Pagnan
authors.forename: Nicola
authors.initials: N
authors.lastname: Semeraro
mesh_terms: D020016:Activated Protein C Resistance / Q000235:genetics*; D000925:Anticoagulants / Q000494:pharmacology; D001323:Autoantibodies / Q000276:immunology*; D025901:Carboxypeptidase B2 / Q000502:physiology; D004789:Enzyme Activation; D005165:Factor V / Q000276:immunology*; D005260:Female; D005342:Fibrinolysis / Q000276:immunology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D008875:Middle Aged; D011486:Protein C / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013917:Thrombin / Q000096:biosynthesis; D019851:Thrombophilia / Q000276:immunology*; D013924:Thrombophlebitis / Q000276:immunology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001323:Autoantibodies; D007074:Immunoglobulin G; D011486:Protein C; D011994:Recombinant Proteins; D005165:Factor V; D006493:Heparin; D025901:Carboxypeptidase B2; D013917:Thrombin; D010959:Tissue Plasminogen Activator