Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Factor VII Deficiency
Factor VII (FVII) deficiency is the most common autosomal recessive rare bleeding disorder. It was first described in 1951 and has an estimated prevalence of 1 in 500,000. The manifestation of bleeding symptoms in FVII deficiency is clinically heterogeneous. Some individuals with FVII deficiency may have mild symptoms, whereas others may have severe and potentially life-threatening bleeding symptoms. Moreover, a proportion of patients remain asymptomatic. Even in one individual with FVII deficiency, there can be a discrepancy between the plasma FVII level and bleeding risk, which can make the prediction of bleeding risk and management challenging.
Pathophysiology
FVII is a 50-kDa, single-chain, vitamin K–dependent serine protease that is synthesized in the liver. FVII is a unique factor in which a small portion of FVII circulates in the plasma as activated FVII (FVIIa) even in the absence of activation during coagulation. On vessel injury, exposed tissue factor (TF) on the vascular lumen interacts with both FVII and FVIIa. This complex of TF and FVII/FVIIa is able to activate factor IX to factor IXa and factor X to factor Xa, which ultimately results in the formation of a fibrin clot. Additionally, FVII can be proteolytically cleaved to FVIIa by several enzymes, including thrombin, factor IXa, factor Xa, and the TF/FVIIa complex. The lipoprotein tissue factor pathway inhibitor is the primary inhibitor of FVIIa.
Genetics
FVII deficiency is inherited in an autosomal recessive pattern. The F7 gene is encoded on chromosome 13 (13q34) and consists of 9 exons encoding 406 amino acids. The majority of F7 gene mutations causing FVII deficiency are missense mutations; splice site mutations, nonsense mutations, and deletions are less common. More than 200 mutations have been identified and can be found in the International Society on Thrombosis and Haemostasis (ISTH) international database for mutations causing rare bleeding disorders ( http://www.isth.org/?MutationsRareBleedin ).
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here