Lab: Fibrinogen

Key Terms

Fibrinogen:

A soluble plasma glycoprotein synthesized by the liver. It's a crucial clotting factor (Factor I) that is converted to fibrin by thrombin during the coagulation cascade.

Fibrin:

An insoluble protein that forms the meshwork of a blood clot.

Hypofibrinogenemia:

A condition characterized by abnormally low levels of fibrinogen in the blood.

Hyperfibrinogenemia:

A condition characterized by abnormally high levels of fibrinogen in the blood.

Coagulation Cascade:

A series of enzymatic reactions involving multiple clotting factors that result in the formation of a stable blood clot.

Basic Science

Normal plasma levels of fibrinogen are usually between 200 - 400 mg/dL. Fibrinogen is a large glycoprotein produced primarily in the liver. It is a key component of the coagulation cascade. When tissue injury occurs and bleeding starts, the cascade is activated. Thrombin cleaves fibrinogen into fibrin monomers. These fibrin monomers then polymerize and form the fibrin mesh, the structural component of the blood clot. Fibrinogen also plays a role in platelet aggregation and wound healing.

Hypofibrinogenemia

Hypofibrinogenemia can be congenital or acquired.

• Congenital deficiencies are rare and include:
  • Afibrinogenemia (complete absence).
  • Hypofibrinogenemia.
• Acquired hypofibrinogenemia is more common and typically secondary to underlying conditions.

• Disseminated Intravascular Coagulation (DIC)
  • Patient History:
    • History of sepsis, trauma, malignancy, pregnancy complications (e.g., placental abruption, amniotic fluid embolism).
    • May report bleeding from multiple sites, including IV sites, gums, nose or urine.
  • Physical Exam Findings:
    • Evidence of active bleeding (petechiae, ecchymoses).
    • Hypotension, tachycardia.
    • May observe signs of the underlying cause (e.g., fever in sepsis).
  • Follow Up Labs:
    • Prothrombin time (PT).
    • Partial thromboplastin time (PTT).
    • D-dimer (elevated).
    • Platelet count (usually low).
    • Peripheral blood smear for schistocytes.
  • Further Diagnostics:
    • Blood cultures to check for sepsis.
    • Imaging based on suspicion of underlying cause.
  • Treatments:
    • Treatment of underlying cause.
    • Transfusion of blood products:
      • Packed red blood cells.
      • Platelets.
      • Cryoprecipitate.
      • Fresh frozen plasma.
    • Recombinant activated factor VIIa or prothrombin complex concentrate.
• Severe Liver Disease
  • Patient History:
    • History of chronic alcohol use.
    • Viral hepatitis.
    • Autoimmune liver disease.
    • May report jaundice, ascites, edema, fatigue.
  • Physical Exam Findings:
    • Jaundice.
    • Ascites.
    • Hepatomegaly.
    • Splenomegaly.
    • Spider angiomata.
  • Follow Up Labs:
    • Elevated liver enzymes (ALT, AST).
    • Bilirubin.
    • Decreased albumin.
    • Prolonged PT/INR.
    • Often thrombocytopenia.
  • Further Diagnostics:
    • Liver ultrasound.
    • Biopsy to assess liver function.
  • Treatments:
    • Supportive care.
    • Treatment of underlying liver disease.
    • Sometimes liver transplantation may be necessary.
    • Vitamin K supplementation.
    • Fresh frozen plasma if bleeding.
• Massive Transfusion
  • Patient History:
    • History of massive bleeding.
    • Significant trauma or surgery.
    • Need for significant blood product administration.
  • Physical Exam Findings:
    • Evidence of continued bleeding.
    • Signs of hypovolemic shock:
      • Hypotension.
      • Tachycardia.
  • Follow Up Labs:
    • PT/INR.
    • PTT.
    • Platelet counts.
    • Fibrinogen levels will be affected and should be checked regularly during massive transfusion protocols.
    • Electrolytes can also be impacted by massive transfusion.
  • Further Diagnostics:
    • Imaging based on underlying cause of bleeding.
  • Treatments:
    • Administration of blood products:
      • Packed red blood cells.
      • Plasma.
      • Cryoprecipitate (to restore fibrinogen).
      • Platelet transfusion as needed.
    • Active assessment and treatment of bleeding cause.
• Congenital Fibrinogen Deficiencies
  • Patient History:
    • Personal or family history of bleeding episodes including:
      • Easy bruising.
      • Menorrhagia.
      • Post-operative bleeding.
    • Congenital conditions are rare and are usually detected in early childhood or infancy.
  • Physical Exam Findings:
    • Minimal findings.
    • May have evidence of mild bruising and other bleeding manifestations.
  • Follow Up Labs:
    • PT/INR.
    • PTT.
    • Fibrinogen activity and antigen levels are necessary to confirm diagnosis.
  • Further Diagnostics:
    • Genetic testing may be useful to identify the specific mutation.
  • Treatments:
    • Cryoprecipitate or fibrinogen concentrate infusions for management of bleeding.
    • Avoidance of antiplatelet agents and other anticoagulants.

Hyperfibrinogenemia

Hyperfibrinogenemia is most often an acute phase reactant and associated with inflammatory and acute processes.

• Acute Inflammation
  • Patient History:
    • Recent history of infection.
    • Tissue injury.
    • Surgery.
    • Autoimmune disorders.
  • Physical Exam Findings:
    • Findings consistent with underlying cause of inflammation.
    • Fever.
    • Local signs of infection.
  • Follow Up Labs:
    • C-reactive protein (CRP).
    • Erythrocyte sedimentation rate (ESR).
    • Complete blood count (CBC) to assess for leukocytosis.
  • Further Diagnostics:
    • Imaging based on suspicion of underlying cause of inflammation.
  • Treatments:
    • Treatment of underlying inflammation or infection.
    • Fibrinogen usually resolves with resolution of the inciting process.
• Pregnancy
  • Patient History:
    • Pregnant status.
    • Fibrinogen levels will rise normally in pregnancy.
  • Physical Exam Findings:
    • Physical exam findings are consistent with the stage of pregnancy.
  • Follow Up Labs:
    • Routine prenatal labs.
    • Fibrinogen levels checked as needed based on history or complication risk.
  • Further Diagnostics:
    • Additional diagnostics as needed based on pregnancy complication risk.
  • Treatments:
    • Usually no treatment is necessary as it is physiologic.
    • Fibrinogen will return to normal postpartum.
• Malignancy
  • Patient History:
    • History of cancer.
    • Weight loss.
    • Fatigue.
    • Other signs concerning for malignancy.
  • Physical Exam Findings:
    • Findings specific to underlying cancer type.
  • Follow Up Labs:
    • CBC.
    • Comprehensive metabolic panel.
    • Other tumor marker labs as appropriate based on suspicion for specific cancer type.
  • Further Diagnostics:
    • Imaging studies for assessment of the extent of malignancy.
  • Treatments:
    • Treatment of the malignancy.
    • Fibrinogen levels should decrease after resolution of the cancer or remission.
• Other conditions
  • Patient History:
    • Other conditions like smoking.
    • Nephrotic syndrome.
    • Hypercholesterolemia.
    • Coronary artery disease.
    • May also be associated with elevated fibrinogen levels.
  • Physical Exam Findings:
    • Findings specific to the underlying condition.
  • Follow Up Labs:
    • Routine labs.
    • Labs specific to the suspected condition such as a lipid panel or urinalysis for nephrotic syndrome.
  • Further Diagnostics:
    • Diagnostic testing appropriate for suspected condition.
  • Treatments:
    • Treatment of the underlying condition.
    • Fibrinogen levels should decrease after resolution of the underlying problem.