Sufficient Thrombin Generation Despite 95% Hemodilution: An In Vitro Experimental Study

Area of Science:

• Hemorrhage management
• Coagulation science

Background:

• Severe bleeding guidelines recommend viscoelastic-test-guided use of coagulation factor concentrates.
• The efficacy and impact of specific factor concentrates on hemostasis require further investigation.

Purpose of the Study:

• To evaluate the effects of fibrinogen concentrate and prothrombin complex concentrate (PCC) substitution on coagulation tests, viscoelastic parameters, and thrombin generation in diluted plasma.
• To assess the impact of these substitutions on hemostatic function under simulated severe bleeding conditions.

Main Methods:

• Platelet-free plasma from healthy volunteers was diluted with crystalloid solution to varying degrees (40-99%).
• Diluted plasma samples were supplemented with fibrinogen concentrate, PCC, a combination, or crystalloid alone.
• Conventional coagulation tests, viscoelastic analysis (e.g., rotational thromboelastometry), and thrombin generation assays were performed.

Main Results:

• Fibrinogen substitution alone significantly shortened clotting time up to 95% dilution compared to combined substitution.
• Clot firmness and endogenous thrombin potential were maintained with fibrinogen substitution but not PCC up to 95% dilution.
• PCC substitution resulted in excessive thrombin generation, indicating a potential risk of hypercoagulability.

Conclusions:

• Fibrinogen concentrate appears more effective than PCC in maintaining hemostatic function in severely diluted plasma.
• Current treatment algorithms recommending PCC for non-anticoagulated bleeding patients may need re-evaluation.
• Adequate hemostasis may be achievable with sufficient thrombin generation even in critically diluted blood.