Background: Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of thromboembolic events and are known to impact coagulation assays and enhance FX-dependent fibrinolysis and plasmin generation.
Simultaneous assessment of the coagulation and fibrinolysis processes could facilitate the global understanding of the pharmacodynamics of DOACs. We have previously reported the performance of the FibWave to assess the impact of DOACs on the clot formation process. In this study the FibWave has been adapted in order to measure both the clot formation and fibrinolysis processes simultaneously.

Aims: To evaluate the suitability of the FibWave for assessing the impact of DOACs on coagulation and fibrinolysis simultaneously.

Methods: DOACs were spiked at final concentrations from 0 to 250 ng/mL in normal pooled plasma. The fibrin clot formation and the fibrinolysis were measured on the FibWave using a mixture of tissue factor, phospholipids and tissue plasminogen activator (tPA).

Results: In absence of tPA, the most influenced parameters in clot formation were the FW-Max₂, FW-Min₂ and FW-Ttpeak for factor Xa (FXa) inhibitors and FW-Ttpeak for dabigatran.
The presence of tPA did not impact significantly the parameters of the clot formation. FXa inhibitors showed a reduction of maximum fibrinolysis velocity (|FW-Min₁|) while dabigatran showed a prolongation of fibrinolysis time (FW-TFib). The time length between fibrinolysis and coagulation velocities (FW-TFib – Ttpeak) was reduced for all anticoagulants (Figure 1).

Schematic curve of initial and first derivative of FibWave (A) and impact of DOACs on fibrinolytic parameters with tPA (B). (A) Curves show the clot formation and fibrinolysis in absence (black curves) and in presence (red curves) of tPA on normal pool plasma (NPP). The fibrinolytic parameters are presented on initial and 1st derivative curves. The last figure shows the clot fibrinolysis waveform in presence of FXa inhibitor (rivaroxaban, 50 ng/mL) and dabigatran (50 ng/mL). (B) The figure represents the impact of DOACs on the maximum fibrinolysis velocity (|FW-Min1|), the fibrinolysis time (FW-TFib) and the time length between fibrinolysis and coagulation velocities (FW-TFib – Ttpeak). The FW-fibrinolysis time (FW-TFib) (in seconds) represents the time when the maximal fibrinolysis velocity is reached.

Conclusions: Thanks to its capacity to assess coagulation and fibrinolysis, the FibWave parameters could be useful for understanding global haemostatic potential and evaluating the bleeding risk from the perspective of fibrinolysis.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/assessment-of-doacs-effect-on-clot-formation-and-fibrinolysis-using-the-fibwave/