**3.6 Dysfibrinogenaemia**

As explained earlier, the main aim of the Coagulation system is to convert fibrinogen (clotting factor I) into fibrin clot. Fibrinogen is encoded by three genes on chromosome 4 (Acharya & Dimichele, 2008; Miesbach et al., 2010). Genetic abnormalities in the fibrinogen genes may lead to lower or no production of fibrinogen (quantitative defects), causing bleeding problems in patients. On the other hand, other genetic abnormalities may lead to the production of fibrinogen molecules with abnormal structure and/or function (qualitative defects). Such abnormalities may negatively affect the binding of fibrinogen with thrombin, the polymerization of fibrin molecules, or the fibrinolytic inactivation by plasmin. This is the condition known as "Dysfibrinogenaemia", which has an autosomal dominant or recessive mode of inheritance (Dahlbäck, 1995; Koeleman et al, 1997; Ehsan & Plumbley, 2002; Laffan & Manning, 2002b; Acharya & Dimichele; 2008). Dysfibrinogenaemia was first reported in 1965 (Beck et al., 1965). Around 60% of cases show no clinical manifestations, while 20% show bleeding problems and 20% show thrombosis (Ehsan & Plumbley, 2002; Miesbach et al., 2010). There are at least 15 different genetic defects affecting the fibrinogen gene that were associated with Dysfibrinogenaemia (Bertina, 1997; Miesbach et al., 2010;). Still, Dysfibrinogenaemia remains a very rare disorder (1% of VTE cases) and more cases should be studied to fully understand the disease (Manucci, 2000; Acharya & Dimichele; 2008).
