Fibrinogen Activity (Factor I Activity)

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