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
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 ...