Anticoagulant drugs targeting factor XI/XIa and coagulation tests: we urgently need reliable pharmacodynamic data

Abstract

Antifactor (F)XI/FXIa anticoagulants under development include antisense oligonucleotides, monoclonal antibodies, and small molecules. They do not require routine monitoring, but knowledge of their impact on coagulation tests is essential in view of their expected widespread use. A concentration-dependent prolongation of activated partial thromboplastin time has been shown but varies according to reagents, and the lack of comprehensive data makes interpretation of this test difficult. Measurement of FXI clotting activity is relevant only in case of treatment with antisense oligonucleotides. Measurement of contact pathway factors, if required, should be performed after multiple dilutions of the plasma sample to overcome any inhibitory effect of the anticoagulant. All other tests used in clinical trials (FXIa, FXI antigenic method, and specific thrombin generation assay) are not implemented in clinical laboratories. More comprehensive information on the effect of anti-FXI/FXIa anticoagulants on coagulation tests is urgently needed to anticipate the use of these drugs once they are approved.

Keywords: APTT; anticoagulants; factor XI inhibitors; factor XIa inhibitors.