Congenital Factor VII Deficiency

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

Hypoproconvertinemia; Congenital Proconvertin Deficiency.

Not precisely known, but estimates range between 1:500,000-1,000,000 live births. Approximately 250 cases have been described in the medical literature.

Autosomal recessive inheritance. 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.

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.

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

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 in four forms: (1) severe life-threatening form (15% of patients) manifesting with neonatal intracranial bleeding and often 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. 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.

Consult a hematologist for recommendations regarding the use of plasma-derived FVII, a heated-vapor treated product safe from viral transmission. However, because of the delay associated with obtaining FVII concentrate, emergency surgery requires use of prothrombin complex concentrates (FII, FVII, FIX, FX), recombinant FVIIa (rFVIIa), or fresh-frozen plasma (FFP). Because the half-life of FVII is only approximately 3 to 4 hours, repeated replacement therapy quite possibly will be necessary (which, in case of FFP, results in huge amounts of volume required). On very rare occasion, patients develop antibodies against rFVIIa, so patients receiving FVII replacement therapy should be monitored for FVII antibodies. Major surgery has been performed with FVII levels as low as 10%; however, maintenance of FVII levels of at least 15 to 25% are recommended for surgical procedures to be performed safely (some sources even recommend 50%).

Obtain a complete blood count and measure PT, PTT, and activity of FVII. Regional anesthesia in general and central neuraxial blockade in particular are best considered contraindicated in these patients. Avoid nasal intubation and nasopharyngeal airways and temperature probes if possible. Also avoid intramuscular injections. Chronic arthropathy in patients with recurrent hemarthros may make positioning difficult. Ensure that appropriate replacement therapy is available before starting surgery or other invasive procedures. Ideally, replacement therapy starts prior to surgery so that therapeutic FVII levels are achieved on time and can be checked before surgery starts.

Vitamin K therapy is of minimal value. Avoid aspirin and nonsteroidal antiinflammatory drugs.

Hemophilia A: Most severe hereditary coagulation disorder resulting from defective synthesis of plasma protein FVIII.

Hemophilia B: A coagulation disorder resulting from defective synthesis of plasma protein FIX.