Accelerated Fibrinolysis: A Tendency to Bleed?

Area of Science:

• Hematology
• Hemostasis and Thrombosis
• Clinical Pathology

Background:

• Hyperfibrinolysis is an under-investigated cause of mild-to-moderate bleeding disorders (MBDs) and bleeding disorders of unknown cause (BDUC).
• Hereditary hyperfibrinolytic disorders can present with mild or severe bleeding symptoms.
• These disorders include deficiencies in α2-antiplasmin (α2-AP) and plasminogen activator inhibitor type 1 (PAI-1), Quebec platelet disorder, and tissue plasminogen activator (tPA) excess.

Purpose of the Study:

• To review the current data on hyperfibrinolysis in MBD and BDUC patients.
• To summarize methods for assessing hyperfibrinolysis.
• To discuss the clinical implications and treatment of hyperfibrinolysis in these patient groups.

Main Methods:

• Review of existing literature on hyperfibrinolysis in MBD and BDUC.
• Analysis of various assessment methods: fibrinolytic factor measurement, global hemostatic assays (viscoelastic testing, turbidity-based plasma clot lysis), and fluorogenic plasmin generation (PG).
• Evaluation of tPA-ROTEM and PG assay findings in BDUC patients.

Main Results:

• Evidence linking hyperfibrinolytic profiles to bleeding severity is inconsistent.
• Increased tPA activity and paradoxical increases in thrombin-activatable fibrinolysis inhibitor and α2-AP were reported in BDUC.
• The tPA-ROTEM assay identified hyperfibrinolysis in up to 20% of BDUC patients; PG analysis showed predictive power in differentiating BDUC patients.

Conclusions:

• Global fibrinolytic assays may help identify hyperfibrinolysis as a cause of bleeding in some MBD/BDUC patients.
• The clinical utility of measuring specific fibrinolytic factors needs further investigation.
• Tranexamic acid is a recommended treatment for hereditary hyperfibrinolysis and for MBD/BDUC patients facing hemostatic challenges.