Congenital Factor VII Deficiency

At a glance

A rare coagulation factor deficit with poor correlation between serum levels and clinical manifestations.

Synonyms

Hypoproconvertinemia; Congenital Proconvertin Deficiency.

Incidence

Unknown, but estimates range between 1-2:1,000,000 live births. Close to 300 cases have been described in the medical literature.

Genetic inheritance

Autosomal recessive. Parental consanguinity is a known risk factor. Heterozygous patients are asymptomatic. No sexual predilection. The factor VII (FVII) gene is located on chromosome 13q34, and more than 120 different mutations have been described.

Pathophysiology

FVII is a vitamin K-dependent clotting factor synthesized in the liver. It is part of the extrinsic clotting cascade and has a half-life of approximately 3 to 4 hours. Specifically, FVII becomes activated (FVIIa) by binding to tissue factor at sites of vascular injury or inflammation. After binding to tissue factor, FVIIa further promotes coagulation by activating FIX and FX. Thus, FVII deficiency prevents initiation of coagulation by the extrinsic pathway and results in a highly variable degree of clinical bleeding, which often does not correlate with plasma levels of FVII, which may be influenced by individual (weight, age, gender), dietary, environmental, and genetic factors. However, generally FVII levels less than 2% of normal values are associated with a significantly increased risk of bleeding. It is generally accepted that an FVII activity level of less than 10% for surgical procedures is considered a risk factor for bleeding complications.

Diagnosis

FVII deficiency is the only hereditary clotting factor deficiency that results in prolonged prothrombin time (PT) and a normal activated partial thromboplastin time (aPTT). However, confirmation of the diagnosis requires a specific FVII assay.

Clinical aspects

Depending on the presence of FVII antigen (FVII:Ag) in the plasma, congenital FVII deficiency can be divided in type I or type II. In type I, FVII:Ag deficiency results from either decreased biosynthesis or accelerated clearance, whereas a dysfunctional FVII:Ag characterizes type II. Generally, features may include hemarthros, menorrhagia, hematuria, epistaxis, gingival bleeding, gastrointestinal bleeding, retroperitoneal hematomas, and fatal cerebral hemorrhages or hematomas. Clinically, the disease has been divided into four forms: (1) severe life-threatening form (15% of patients) manifesting with neonatal intracranial bleeding with a frequently lethal course in infancy; (2) severe hemorrhagic form (20%) with recurrent hemarthros and consequently chronic arthropathy; (3) mild, late-onset form (60%) with postoperative cutaneous or mucosal bleeding; and (4) asymptomatic form (20%). Exclude acquired FVII deficiency secondary to liver disease, vitamin K-deficiency (warfarin therapy, malabsorption), and, rarely, severe infections. Paradoxically, a few patients develop thrombotic complications such as pulmonary embolus and/or myocardial infarction.

Precautions before anesthesia

Consult a hematologist for recommendations regarding the use of plasma-derived FVII, a heated-vapor treated product safe from viral ...