Inherited Thrombophilia in the Era of Direct Oral Anticoagulants.

Lina Khider,Laetitia Mauge,Nicolas Gendron

doi:10.3390/ijms23031821

Abstract

Severe inherited thrombophilia includes rare deficiencies of natural anticoagulants (antithrombin and proteins C and S) and homozygous or combined factor V Leiden and FII G20210A variants. They are associated with a high thrombosis risk and can impact the duration of anticoagulation therapy for patients with a venous thromboembolism (VTE) event. Therefore, it is important to diagnose thrombophilia and to use adapted anticoagulant therapy. The widespread use of direct anticoagulants (DOACs) for VTE has raised new issues concerning inherited thrombophilia. Concerning inherited thrombophilia diagnosis, DOACs are directed toward either FIIa or FXa and can therefore interfere with coagulation assays. This paper reports DOAC interference in several thrombophilia tests, including the assessment of antithrombin, protein S, and protein C activities. Antithrombin activity and clot-based assays used for proteins C and S can be overestimated, with a risk of missing a deficiency. The use of a device to remove DOACs should be considered to minimize the risk of false-negative results. The place of DOACs in the treatment of VTE in thrombophilia patients is also discussed. Available data are encouraging, but given the variability in thrombosis risk within natural anticoagulant deficiencies, evidence in patients with well-characterized thrombophilia would be useful.

Highlights

Venous thromboembolic disease (VTD) is a multifactorial disease resulting from the interaction between environmental, clinical, and biological risk factors
Thrombophilia testing may be significantly affected by even small amounts of Direct oral anticoagulants (DOACs)
AT activity can be studied with either factor Xa (FXa)- or FIIa-based assays depending on the target of the DOACs

Summary

Introduction

Venous thromboembolic disease (VTD) is a multifactorial disease resulting from the interaction between environmental, clinical, and biological risk factors. Biological thrombophilia corresponds to the presence of an acquired or inherited biological risk factor predisposing the patient to venous thromboembolism (VTE) [1]. Thrombophilia assessment can be useful for the propositus and help in the assessment of the benefit/risk ratio in terms of the duration of anticoagulant treatment. In some cases, such as antithrombin (AT) deficiency, it can be useful for symptomatic patients treated with heparin (increasing heparin doses to achieve therapeutic anticoagulation) and for asymptomatic relatives, especially women of childbearing age (prevention of thrombosis during pregnancy and in the case of estrogen pills). The present review does not discuss acquired thrombophilia such as APS, focusing only on the most frequent inherited thrombophilia

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