hypofibrinolysis

Hypofibrinolysis is a state of reduced fibrinolytic activity, in which the breakdown of fibrin clots is diminished. The fibrinolytic system normally dissolves thrombi through plasmin, generated from plasminogen by tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator. In hypofibrinolysis, plasmin generation or activity is impaired, leading to clots that persist longer than normal.

Common mechanisms include increased inhibition of plasminogen activation via plasminogen activator inhibitors (PAI-1, PAI-2), enhanced thrombin-activatable fibrinolysis inhibitor (TAFI) activity, elevated levels of alpha2-antiplasmin, reduced tPA release, or plasminogen deficiency. Genetic factors and acquired conditions may contribute. Hypofibrinolysis exists on a spectrum from mild reductions to marked impairment.

Etiologies are diverse and can be acquired or inherited. Acquired states associated with reduced fibrinolysis include obesity, metabolic syndrome, aging, cardiovascular disease, cancer-associated thrombosis, and chronic inflammatory conditions; inherited deficiencies affecting plasminogen or its regulators may also present with reduced fibrinolysis.

Diagnosis is typically functional and may include prolonged euglobulin clot lysis time (ECLT) or reduced fibrinolysis on thromboelastography (TEG/ROTEM). Specialized plasmin generation assays can quantify plasmin activity. Normal standard coagulation tests do not exclude hypofibrinolysis.

Clinical significance: hypofibrinolysis is associated with an increased risk of venous and arterial thrombosis due to diminished clot breakdown. It can complicate cardiovascular disease, cancer-associated thrombosis, and other inflammatory states.

Management focuses on treating underlying conditions and reducing thrombotic risk with appropriate anticoagulation when indicated. Antifibrinolytic therapy worsens hypofibrinolysis and is generally avoided unless there is a separate bleeding indication.