• During fibrinolysis, cross-linked fibrin clots (formed from fibrin monomers which were activated from fibrinogen) are broken down into fibrin degradation products (FDPs) (one of which is D-dimer). This reaction is enhanced by plasmin (converted from plasminogen).
• Fibrinogen and D-dimer levels are routinely measured to assess fibrinolytic and thromboembolic activities.
• Fibrinogen level is low when there is a decrease in its production (e.g. dysfuntional liver, inherited disorders) or when there is an increase in its consumption (due to coagulopathy) or destruction (due to autoimmune reactions) (e.g. DIC, HLH, autoimmune disorders).
• D-dimer level is high when fibrinolytic activity level is high (e.g. DIC, trauma, malignancy), which might be associated with increased thromboembolism (e.g. DVT, PE).
• Fibrinogen and D-dimer are also positive acute phase reactants (APRs) therefore both level are elevated during inflammation. For this reason, fibrinogen level might be normal in cases where there are concurrently inflammatory and thromboembolic processes (e.g. ischemia due to vasoocclusion).
• Fibrinolysis is regulated by various factors including:
Activators: plasmin, plasminogen activator (t-PA)
Inhibitors: alpha-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), lipoprotein Lp(a), thrombin activatable fibrinolysis inhibitor (TAFI)
• Any deficiency or overproduction of either of fibrinolytic activator or inhibtor can result in abnormal fibrinolysis.
Hyperfibrinolysis: with increased risk of bleeding
Hypofibrinolysis: with increased risk of thrombosis
• Comparing to primary fibrinolysis, secondary fibrinolysis might also present with thrombocytopenia, decreased antithrombin level, and/or prolonged clotting times due to its systemic effect on both platelet and coagulation cascade in addition to the fibrinolytic system. Red cell fragments or schistocytes are also seen in DIC but not primary fibrinolysis.
