Background: In FXI-deficiency, bleeding is unpredictable and poorly correlated to FXI plasmatic levels as measured by aPTT-based clotting assays. Current treatment options for patients with FXI-deficiency include the use of commercial FXI-concentrates, which are associated with an increased thrombotic risk. In absence of a laboratory tool able to predict the bleeding risk in FXI-deficiency, clinical management of these patients remains empiric and carries the risk of under- or over-treatment. Assays able to monitor the hemostatic potential of FXI-replacement therapy would have a high clinical value.

Aims: We evaluated the utility of the recently marketed global coagulation assay Thrombodynamics [(TD), Hemacore, Moscow, Russia] for monitoring the hemostatic potential of FXI-deficient patients after FXI-replacement therapy with a commercial FXI-concentrate (Hemoleven®, LFB-Biomedicaments, Les Ulis, France).

Methods: TD analyzes the spatio-temporal propagation of tissue factor (TF) dependent and independent coagulation. We first established reference ranges for thrombin generation (TG) and fibrin clot formation (FCF) parameters analyzing plasma of 53 healthy controls. Subsequently, we investigated the effect on coagulation parameters of increasing doses of Hemoleven® spiked to FXI-deficient plasma. Finally, we measured the hemostatic potential at baseline and after FXI-replacement in five patients treated with Hemoleven® (1000 IU) prior to a planned intervention (n=7).

Results: During the TF-independent phase of coagulation, TG and FCF increased dose dependently after in vitro FXI spiking. Similarly, TG and FCF were strongly increased in patients receiving Hemoleven® already at FXI-concentrations of 20% and shifted towards hypercoagulation at FXI-levels of about 30% (see figure below).

Conclusions: TD appears to be useful for assessing the hemostatic potential of patients after administration of Hemoleven® and for monitoring replacement therapy, thus representing the first laboratory tool allowing patient-tailored management in FXI-deficiency. Our study supports the use of very low doses of Hemoleven®, aiming to FXI plasma levels ≤20%, which is lower than currently recommended (30-40%).

[Figure: Rate of clot growth (V) and amplitude of thrombin peak (Ast) at baseline and after infusion with Hemoleven®. Shaded zone = normal values]

« Back to ISTH 2020 Congress

ISTH Congress Abstracts - https://abstracts.isth.org/abstract/usefulness-of-tissue-factor-independent-coagulation-parameters-for-monitoring-fxi-concentrate-replacement-in-patients-with-fxi-deficiency/