title: Whole blood clots are more resistant to lysis than plasma clots--greater efficacy of rivaroxaban.
abstract: BACKGROUND
  Defective thrombolysis, a thrombotic risk factor, can be attributed to the formation of a compact clot poorly accessible to fibrinolytic enzymes. Venous thrombi, rich in red blood cells (RBCs), and arterial thrombi containing various amounts of RBCS, plasma and whole blood (WB) clot permeability and degradability were compared. The effect of rivaroxaban, a potent direct factor Xa inhibitor, was also evaluated.
  
  
  METHODS
  Fibrin permeability was determined by flow measurement through the clot. Clot degradability was evaluated by the amount of D-dimer generated by clot perfusion with plasminogen and tissue plasminogen activator. Fibrin clot structure was assessed by confocal microscopy.
  
  
  RESULTS
  WB clot permeability (KS) and degradability were 6.7- and 38-fold lower, respectively, compared with plasma clots. This is attributed to 1) occlusion of fibrin pores by RBCs and 2) a consistent increase in thrombin generation due to platelets and RBCs inducing formation of a tighter clot. Rivaroxaban added to plasma or WB before clotting, in reducing thrombin generation, led to the formation of a looser clot that is more degradable by fibrinolytic enzymes. Permeability and degradability of whole blood clots formed in the presence of rivaroxaban were very similar to those of plasma clots.
  
  
  CONCLUSIONS
  The resistance to fibrinolysis of WB clots was reduced considerably when clots were formed with rivaroxaban. These results may have implications for the development of antithrombotic agents.
authors: UMRS 872 INSERM, Université Pierre et Marie Curie Paris VI and Université René Descartes, Paris, France.
authors: Rémi
authors: R
authors: Varin
authors: Shahsultan
authors: S
authors: Mirshahi
authors: Pezhman
authors: P
authors: Mirshahi
authors: Christophe
authors: C
authors: Klein
authors: Jovid
authors: J
authors: Jamshedov
authors: Jean
authors: J
authors: Chidiac
authors: Elisabeth
authors: E
authors: Perzborn
authors: Massoud
authors: M
authors: Mirshahi
authors: Claudine
authors: C
authors: Soria
authors: Jeannette
authors: J
authors: Soria
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001769:Blood / Q000187:drug effects*; D001777:Blood Coagulation; D001792:Blood Platelets / Q000166:cytology; D004912:Erythrocytes / Q000166:cytology; D005176:Factor XIII / Q000737:chemistry; D005337:Fibrin / Q000737:chemistry*; D005338:Fibrin Fibrinogen Degradation Products / Q000737:chemistry; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D009025:Morpholines / Q000627:therapeutic use*; D010539:Permeability; D010949:Plasma / Q000187:drug effects*; D012307:Risk Factors; D000069552:Rivaroxaban; D013876:Thiophenes / Q000627:therapeutic use*; D013917:Thrombin / Q000378:metabolism; D015912:Thrombolytic Therapy / Q000379:methods*; D013925:Thromboplastin / Q000737:chemistry; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism; D013997:Time Factors
chemical_list: D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D009025:Morpholines; D013876:Thiophenes; C036309:fibrin fragment D; D005337:Fibrin; D005176:Factor XIII; D013925:Thromboplastin; D000069552:Rivaroxaban; D013917:Thrombin