**5.1. Fibrinogen deficiency**

Fibrinogen is a 340 kDa hexamer assembled by the combination of 3 homologous polypeptide chains (Aα, Bβ and γ) [57]. Fibrinogen plays an important role in clot formation where thrombin converts fibrinogen into soluble fibrin which further forms an insoluble polymer mesh, fibrin also plays an active role in platelet aggregation by binding to glycoprotein IIb/ IIIa on the activated platelets [57]. The genes encoding for Bβ (FGB), Aα (FGA) and γ (FGG) are located on chromosome 4 from centromere to telomere [58]. Fibrinogen is primarily synthesized in liver [59]. Fibrin deficiency is identified as two phenotypes termed as afibrinogenemia/hypofibrinogenemia and it is characterized by low plasma and platelet fibrinogen antigens whereas, dys/hypodysfibrinogenemia is characterized by the deficiency of functional fibrinogen levels [60, 61]. Afibrinogenemia is detected by prolonged prothrombin time, thrombin time, activated partial thromboplastin time, impaired platelet adhesion and impaired platelet aggregation induced by ADP [60, 62]. Clinical manifestations of fibrinogen include umbilical stump bleeding, possible gastrointestinal bleeding, recurrent episodes of intracranial hemorrhage [60, 63]. Treatment for fibrinogen deficiency include replacement therapy by cryoprecipitate [63].

#### **5.2. Prothrombin deficiency**

Prothrombin is a vitamin K dependent glycoprotein synthesized in the liver [64]. Prothrombin is encoded by 21 kb gene present on chromosome 11 [65, 66]. Prothrombin deficiency is observed in 1 in 2 million [65]. Prothrombin deficiency is classified into two types, hypoprothrombinemia caused by low prothrombin production and dysprothrombinemia is caused by deficiency of functional prothrombin [65]. Hypoprothrombinemia with less than 5% prothrombin antigen is characterized by severe bleeding whereas dysprothrombinemia causes variable bleeding tendencies [65]. Treatments for prothrombin deficiency include prothrombin complex concentrate and fresh frozen plasma [67].
