Fibrinogen, also referred to as factor I, is a 340-kilodalton glycoprotein that is produced by the liver.6
Fibrinogen has a plasma half-life of about four days. Proteolytic
conversion of fibrinogen to fibrin occurs through both the extrinsic and
intrinsic pathways.6 Severe fibrinogen deficiency should be
considered when a patient with bleeding history has both extended
protime (PT) and activated partial thromboplastin time (aPTT).7,8
Mild deficiency may not produce prolongation of either the aPTT or PT
and, therefore, fibrinogen activity should be measured in individuals
with a bleeding tendency even when the aPTT and PT are in the normal
reference interval.
Congenital afibrinogenemia, a condition
associated with the complete absence of fibrinogen, is rare with only
about 150 cases reported in the literature.6,7 Fibrinogen deficiency is inherited as an autosomal recessive trait.7,8
Afibrinogenemia occurs in individuals who are homozygous or doubly
heterozygous for mutations. These individuals have infinite protime and
aPTT results due to the inability to produce fibrin. Approximately 25%
of patients with afibrinogenemia have mild thrombocytopenia.7
Individuals
who are heterozygous for congenital fibrinogen deficiency are usually
asymptomatic unless their fibrinogen levels fall to <50 mg/dL.7 Both functional (activity) and antigenic levels are diminished in these individuals.7 Fibrinogen deficiency affects both males and females with a prevalence that is equal in all ethnic groups.7
Acquired deficiencies occur in individuals with significant hepatic
dysfunction, renal disease, and after L-asparaginase therapy.6
Diminished levels can also be seen in patients with disseminated
intravascular coagulation (DIC) or who are undergoing thrombolytic
therapy.6 Fibrinogen is one of the major determinants of the
erythrocyte sedimentation rate and individuals with afibrinogenemia
typically have greatly extended sedimentation rates.7
Individuals
with dysfibrinogenemia have fibrinogen that is qualitatively defective
with low functional fibrinogen levels (activity) and normal or decreased
antigenic levels.6 Congenital dysfibrinogenemia is inherited as an autosomal dominant mutation.6
A number of disfibrinogenemic defects have been identified with a
variety of manifestations including abnormal fibrin polymerization,
impaired fibrinopeptide release, abnormal fibrin stabilization, and
abnormal fibrin clot lysis.6,7 Fibrinogen activity and
antigen levels are useful in the diagnosis of dysfibrinogenemia since
these individuals often have diminished activity relative to antigen
levels.8 Typically, dysfibrinogenemia is associated with an elevated thrombin time and greatly elevated reptilase time.
Individuals with afibrinogenemia have a bleeding tendency of varying severity.7 Symptoms often start in early infancy with umbilical cord bleeding, intracerebral hemorrhage, or bleeding at circumcision.6-8
Individuals with afibrinogenemia also suffer from deep muscle and joint
bleeding and other mucous membrane bleeding throughout life.6 Women with afibrinogenemia typically do not experience menorrhagia.8
Patients with heterozygous hypofibrinogenemia usually have a minimal
history of bleeding with symptoms only observed after major surgery or
trauma.6,7 Approximately 50% of individuals with dysfibrinogenemia are asymptomatic suffering neither bleeding nor thrombosis.6,7
These individuals are usually detected when prolonged clotting times
are discovered as a result of routine laboratory testing. About one in
four will suffer prolonged bleeding after surgery and approximately 20%
will have an increased tendency toward thrombosis.6
A
number of clinical and epidemiological studies have revealed a
consistent association between elevated fibrinogen levels and increased
risk for atherosclerotic vascular disease;11 however, it
remains to be determined whether increased fibrinogen acts as a mediator
of arterial thrombosis or simply reflects the inflammation associated
with atherosclerosis.11
