The aim of this study was to investigate the structure and function of fibrinogen obtained from a patient with normal coagulation times and idiopathic thrombophilia. This was done by SDS-PAGE and DNA sequence analyses, scanning electron microscopy, fibrinopeptide release, fibrin polymerisation initiated by thrombin and reptilase, fibrinolysis, and platelet aggregometry. A novel heterozygous point mutation in the fibrinogen Aα chain, Phe98 to Ile, was found and designated as fibrinogen Vizovice. The mutation, which is located in the RGDF sequence (Aα 95-98) of the fibrinogen coiled-coil region, significantly affected fibrin clot morphology. Namely, the clot formed by fibrinogen Vizovice contained thinner and curled fibrin fibers with reduced length. Lysis of the clots prepared from Vizovice plasma and isolated fibrinogen were found to be impaired. The lysis rate of Vizovice clots was almost four times slower than the lysis rate of control clots. In the presence of platelets agonists the mutant fibrinogen caused increased platelet aggregation. The data obtained show that natural mutation of Phe98 to Ile in the fibrinogen Aα chain influences lateral aggregation of fibrin protofibrils, fibrinolysis, and platelet aggregation. They also suggest that delayed fibrinolysis, together with the abnormal fibrin network morphology and increased platelet aggregation, may be the direct cause of thrombotic complications in the patient associated with pregnancy loss.
- MeSH
- agregace trombocytů MeSH
- batroxobin metabolismus MeSH
- bodová mutace MeSH
- časové faktory MeSH
- dospělí MeSH
- fibrin metabolismus MeSH
- fibrinogen genetika metabolismus MeSH
- fibrinolýza MeSH
- hemokoagulace MeSH
- heterozygot MeSH
- konformace proteinů MeSH
- lidé MeSH
- samovolný potrat krev MeSH
- těhotenství MeSH
- trombin metabolismus MeSH
- trombofilie krev genetika MeSH
- vyšetření krevní srážlivosti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- reptilázový čas, aktivovaný parciální tromboplastinový čas,
- MeSH
- batroxobin MeSH
- heparin škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- monitorování fyziologických funkcí MeSH
- trombinový čas využití MeSH
- trombofilie prevence a kontrola MeSH
- vyšetření krevní srážlivosti využití MeSH
- Check Tag
- lidé MeSH
- MeSH
- batroxobin izolace a purifikace krev MeSH
- klinické chemické testy MeSH
- lidé MeSH
- trombocytopenie diagnóza MeSH
- Check Tag
- lidé MeSH
