At the Roche Diagnostics-sponsored satellite symposium ‘From Basic Research to Clinical Data: the Future of Patient Management’ hosted during the International Society for Haemostasis (ISTH) 2021 congress, Prof. Jonathan Douxfils discussed the value of monitoring direct oral anticoagulants (DOAC) and contact pathway inhibitors.

While DOACs were developed without the need for routine laboratory monitoring, the assessment of drug exposure and anticoagulant effect are useful in certain clinical situations. For example, Prof. Douxfils highlighted the importance of monitoring the plasma concentration of DOACs to assess bleeding or thrombosis recurrence, with studies having shown an association between higher DOAC plasma levels and bleeding complications without additive thrombotic protection. Among patients receiving DOACs, recent analyses have found a higher prevalence of bleeding events in high responders and thrombotic events in low responders. Given this inter-individual variability, anticoagulation monitoring may allow for individualised management to optimise patient outcomes. Other clinical settings for which measuring DOACs are of interest include before invasive procedures including emergent surgery, to guide antidote administration and also in patients with unpredictable pharmacokinetics, such as those with extreme body weights. For detailed laboratory guidance on the measurement of DOACs, please see recommendations from the International Council for Standardisation in Haematology [1,2].

Contact pathway inhibitors, typically targeting Factors XI or XII which play an important role in thrombosis, represent promising new anticoagulation therapies. A multitude of strategies for Factor XI/XII inhibition have been proposed including the use of small peptidomimetic or peptide inhibitors, monoclonal antibodies, antisense oligonucleotides and aptamers. As Factor XI is activated by thrombin and plays a role in amplifying thrombin generation, Factor XI inhibiting agents such as osocimab have been associated with bleeding rates comparable to enoxaparin and higher than apixaban thus, further evidence is needed as to whether routine or occasional biological monitoring could be incorporated. The development of specific tests may be recommended for these new therapeutic agents, with approaches potentially based on chromogenic, fluorogenic, clot-based, antigenic detection and global haemostasis tests.

References:

[1] Gosselin RC, et al. Thromb Haemost 2018;118:437-450
[2] Douxfils J, et al. Thromb Haemost 2021;121:1008–1020.