Fibrinogen Antigen

Fibrinogen, also referred to as factor I, is a 340 kilodalton glycoprotein that is produced by the liver.¹ Fibrinogen has a plasma half-life of about four days. Proteolytic conversion of fibrinogen to fibrin occurs through both the extrinsic and intrinsic pathways.¹ Fibrinogen deficiency should be considered when a patient with bleeding history has both extended protime (PT) and activated partial thromboplastin time (aPTT).^2,3 Fibrinogen activity should be measured when a patient has a history of bleeding and the PT and aPTT are normal, as these assays are generally insensitive to fibrinogen deficiency unless levels drop to <100 mg/dL.

Congenital afibrinogenemia, a condition associated with the complete absence of fibrinogen, is rare with only about 150 cases reported in the literature.^1,2 Fibrinogen deficiency is inherited as an autosomal recessive trait.^2,3 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.²

Individuals who are heterozygous for congenital fibrinogen deficiency are usually asymptomatic unless their fibrinogen levels fall to <50 mg/dL.² Both functional (activity) and antigenic levels are diminished in these individuals.² Fibrinogen deficiency affects both males and females with a prevalence that is equal in all ethnic groups.² Acquired deficiencies occur in individuals with significant hepatic dysfunction, renal disease, and after L-asparaginase therapy.¹ Diminished levels can also be seen in patients with disseminated intravascular coagulation (DIC) or who are undergoing thrombolytic therapy.¹ Fibrinogen is one of the major determinants of the erythrocyte sedimentation rate and individuals with afibrinogenemia typically have greatly extended sedimentation rates.²

Individuals with dysfibrinogenemia have fibrinogen that is qualitatively defective with low functional fibrinogen levels (activity) and normal or decreased antigenic levels.¹ Congenital dysfibrinogenemia is inherited as an autosomal dominant mutation.¹ 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.^1,2 Fibrinogen activity and antigen levels are useful in the diagnosis of dysfibrinogenemia since these individuals often have diminished activity relative to antigen levels.³ Reptilase time is generally greatly prolonged, to a greater degree than prolongation of the thrombin time.

Individuals with afibrinogenemia have bleeding tendencies of varying severity.² Symptoms often start in early infancy with umbilical cord bleeding, intracerebral hemorrhage, or bleeding at circumcision.^1-3 Individuals with afibrinogenemia also suffer from deep muscle and joint bleeding and other mucous membrane bleeding throughout life.¹ Women with afibrinogenemia typically do not experience menorrhagia.³ Patients with heterozygous hypofibrinogenemia usually have a minimal history of bleeding with symptoms only observed after major surgery or trauma.^1,2 Approximately 50% of individuals with dysfibrinogenemia are asymptomatic.^1,2 These individuals are usually detected when prolonged clotting times are discovered as a result of routine laboratory testing; however, about one in four will suffer prolonged bleeding after surgery and approximately 20% will have an increased tendency toward thrombosis.¹

A number of clinical and epidemiological studies have revealed a consistent association between elevated fibrinogen levels and increased risk for atherosclerotic vascular disease;⁵ however, it remains to be determined whether increased fibrinogen acts as a mediator of arterial thrombosis or simply reflects the inflammation associated with atherosclerosis.⁵