How is hyperfibrinolysis detected and treated?

Detection and Treatment of Hyperfibrinolysis

Hyperfibrinolysis is best detected using viscoelastic hemostatic assays such as thromboelastography (TEG) or rotational thromboelastometry (ROTEM), with treatment primarily consisting of antifibrinolytic agents like tranexamic acid. 1

Detection Methods

Viscoelastic Tests

• TEG and ROTEM currently provide the best point-of-care measures of fibrinolysis, with results available within 60 minutes 1
• TEG thresholds between 3% and 7.5% LY30 (percent degradation of clot 30 minutes after reaching maximum amplitude) are associated with increased risk for massive transfusion and mortality 1, 2
• ROTEM can detect hyperfibrinolysis using parameters such as maximum lysis >15% 3
• Tissue factor-triggered ROTEM tests (EXTEM, FIBTEM) are more sensitive than contact-activated kaolin-TEG in identifying hyperfibrinolysis 3
• FIBTEM (tissue factor activation with platelet inhibition) shows enhanced sensitivity to hyperfibrinolysis detection compared to EXTEM 3

Patterns and Prognostic Value

• Different hyperfibrinolysis patterns correlate with mortality: fulminant breakdown within 30 minutes (100% mortality), intermediate HF of 30-60 minutes (91% mortality), and late HF after 60 minutes (73% mortality) 4
• Hyperfibrinolysis combined with hemorrhagic shock, low platelet count, and prolonged clot formation time in ROTEM are independent predictors of death 4

Limitations of Detection Methods

• Standard viscoelastic tests may be insensitive to moderate yet clinically significant fibrinolytic activation 5
• Viscoelastic tests are performed at 37°C and cannot assess effects of hypothermia on coagulation 1, 2
• TEG/ROTEM cannot detect von Willebrand disease or disorders affecting endothelial adherence 1, 2
• Standard TEG is insensitive to antiplatelet agents and cannot reliably detect platelet dysfunction 1, 2

Modified Protocols

• Addition of tissue plasminogen activator (tPA) to ROTEM can enhance detection of both hypofibrinolysis and hyperfibrinolysis 6
• Modified protocols with tPA and plasmin challenge may improve calibration, but are not currently FDA approved in the USA 1

Treatment Approaches

First-Line Treatment: Antifibrinolytics

• Tranexamic acid is the primary treatment for hyperfibrinolysis 1, 7
• Recommended dosing of tranexamic acid is 1g loading dose over 10 minutes followed by 1g over 8 hours 7
• Early administration of antifibrinolytic agents may be beneficial for hemorrhage control in trauma patients with hyperfibrinolysis 1

Alternative Treatment: Epsilon-Aminocaproic Acid

• For acute bleeding syndromes due to elevated fibrinolytic activity, administer 4-5g of epsilon-aminocaproic acid in 250mL of diluent during the first hour, followed by continuous infusion at 1g per hour 8
• Treatment typically continues for about 8 hours or until bleeding is controlled 8
• Rapid intravenous administration should be avoided as it may induce hypotension, bradycardia, and/or arrhythmia 8

Additional Considerations

• Recombinant activated factor VII (rFVIIa) may be valuable in hyperfibrinolysis as it reduces clot susceptibility to fibrinolysis partly by inducing thrombin-activated fibrinolytic inhibitor (TAFI) 1
• In trauma patients with evidence of hemorrhagic shock, early empiric tranexamic acid is recommended according to European guidelines 5
• Monitoring should continue with repeat viscoelastic testing to guide ongoing treatment 7

Clinical Context and Prevalence

• Hyperfibrinolysis may be more common in trauma patients than previously realized, with approximately 20% of multi-trauma patients with massive bleeding showing marked hyperfibrinolysis 1
• Hyperfibrinolysis is a key component of acute traumatic coagulopathy and associated with poor clinical outcomes 5
• Fibrinolysis activation occurs almost universally after severe trauma 5
• Hyperfibrinolysis is one of the main causes of non-surgical bleeding during liver transplantation 3

Important Precautions

• Epsilon-aminocaproic acid should NOT be administered without a definite diagnosis and/or laboratory finding indicative of hyperfibrinolysis 8
• Inhibition of fibrinolysis by aminocaproic acid may theoretically result in clotting or thrombosis, though definitive evidence linking the drug to intravascular clotting is lacking 8
• Do not rely solely on conventional coagulation tests (PT, aPTT) as they may not correlate well with clinical bleeding or TEG parameters 7
• Do not delay treatment while waiting for laboratory results in cases of severe bleeding 7