title: Lytic resistance of fibrin containing red blood cells.
abstract: OBJECTIVE
  Arterial thrombi contain variable amounts of red blood cells (RBCs), which interact with fibrinogen through an eptifibatide-sensitive receptor and modify the structure of fibrin. In this study, we evaluated the modulator role of RBCs in the lytic susceptibility of fibrin.
  
  
  RESULTS
  If fibrin is formed at increasing RBC counts, scanning electron microscopy evidenced a decrease in fiber diameter from 150 to 96 nm at 40% (v/v) RBCs, an effect susceptible to eptifibatide inhibition (restoring 140 nm diameter). RBCs prolonged the lysis time in a homogeneous-phase fibrinolytic assay with tissue plasminogen activator (tPA) by up to 22.7±1.6%, but not in the presence of eptifibatide. Confocal laser microscopy using green fluorescent protein-labeled tPA and orange fluorescent fibrin showed that 20% to 40% (v/v) RBCs significantly slowed down the dissolution of the clots. The fluorescent tPA variant did not accumulate on the surface of fibrin containing RBCs at any cell count above 10%. The presence of RBCs in the clot suppressed the tPA-induced plasminogen activation, resulting in 45% less plasmin generated after 30 minutes of activation at 40% (v/v) RBCs.
  
  
  CONCLUSIONS
  RBCs confer lytic resistance to fibrin resulting from modified fibrin structure and impaired plasminogen activation through a mechanism that involves eptifibatide-sensitive fibrinogen-RBC interactions.
authors: Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
authors: Nikolett
authors: N
authors: Wohner
authors: Péter
authors: P
authors: Sótonyi
authors: Raymund
authors: R
authors: Machovich
authors: László
authors: L
authors: Szabó
authors: Kiril
authors: K
authors: Tenekedjiev
authors: Marta M C G
authors: MM
authors: Silva
authors: Colin
authors: C
authors: Longstaff
authors: Krasimir
authors: K
authors: Kolev
mesh_terms: D000077542:Eptifibatide; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism* / Q000648:ultrastructure; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D010455:Peptides / Q000494:pharmacology; D010958:Plasminogen / Q000378:metabolism; D039341:Receptors, Fibrinogen / Q000187:drug effects / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013927:Thrombosis / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D010455:Peptides; D039341:Receptors, Fibrinogen; D011993:Recombinant Fusion Proteins; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D000077542:Eptifibatide