title: In vitro fibrin clot formation and fibrinolysis using heterozygous plasma fibrinogen from gammaAsn319, Asp320 deletion dysfibrinogen, Otsu I.
abstract: BACKGROUND
  We have reported a heterozygous dysfibrinogenemia, fibrinogen Otsu I, caused by the deletion of gammaAsn319 and gammaAsp320, which was originally identified in the dysfibrinogen Vlissingen/Frankfurt IV (V/FIV) associated with thrombosis. Unlike the V/FIV family, the Otsu propositus showed no thrombotic tendencies. To analyze the relationship between thrombosis and the heterozygous plasma variant fibrinogen, we used purified plasma fibrinogen from the Otsu patient and compared it with a normal control.
  
  
  METHODS
  Thrombin-induced fibrin clot formation and clot structure were observed by fibrin polymerization and scanning electron microscopy, respectively. For in vitro observation of fibrinolysis, plasmin generation and clot lysis assays were performed by the addition of tissue type plasminogen activation (tPA) and plasminogen.
  
  
  CONCLUSIONS
  Polymerization of Otsu was markedly impaired, while fibrin fibers were much thicker and the density of the bundles of fibrin fibers was less and porous compared with normal. Lysis of the Otsu clot was not significantly different from normal when a tPA and plasminogen mixture was overlaid onto the clots. For Otsu, the penetration of the tPA/plasminogen mixture into the clot was much faster than normal and the protection against plasmin cleavage was impaired; however, tPA-induced plasmin activation of the Otsu fibrin was slower than that of normal fibrin, resulting in a clot lysis of Otsu similar to normal.
authors.affiliation: Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, 3-1-1 Asahi, Matsumoto, Japan. fterasa@shinshu-u.ac.jp
authors.forename: Fumiko
authors.initials: F
authors.lastname: Terasawa
authors.forename: Satomi
authors.initials: S
authors.lastname: Kani
authors.forename: Minoru
authors.initials: M
authors.lastname: Hongo
authors.forename: Nobuo
authors.initials: N
authors.lastname: Okumura
mesh_terms: D000347:Afibrinogenemia / Q000235:genetics*; D001777:Blood Coagulation / Q000276:immunology*; D018389:Codon, Nonsense / Q000235:genetics; D015241:Fibrinogens, Abnormal / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D005342:Fibrinolysis / Q000276:immunology*; D017353:Gene Deletion; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D018389:Codon, Nonsense; D015241:Fibrinogens, Abnormal