The relationship between DOAC levels and clinical outcomes: The measures tell the tale–Response from original authors Lijfering et al

Abstract

Brunetti and Bo 1 raised a number of comments to our recently published Forum Article 2 on the potential benefits of measuring anticoagulation levels in patients who use direct oral anticoagulants (DOACs). We would like to respond to these comments. First, Brunetti and Bo argue that "major bleeding incidences observed in DOAC experimental and observational studies are quite reassuring", thereby referring to major bleeding rates (1.6%-2.3% per year)

The myths behind DOAC measurement: Analyses of prescribing information from different regulatory bodies and a call for harmonization

“…The current absence of strong evidence provided by clinical studies to support the monitoring or measurement of DOAC levels may seem a limiting factor for test implementation, even in off‐label uses of these drugs or drug use in special populations such as the frail elderly, morbidly obese, and others 30 . Nevertheless, the absence of evidence is not the same as the evidence of a absence and more and more scientific data support the assumption that there is room for improvement in decreasing the number of bleeds (and herewith associated mortality, comorbidity, and health care costs) among patients who are anticoagulated with DOACs 17,31,32 …”

“…30 Nevertheless, the absence of evidence is not the same as the evidence of a absence and more and more scientific data support the assumption that there is room for improvement in decreasing the number of bleeds (and herewith associated mortality, comorbidity, and health care costs) among patients who are anticoagulated with DOACs. 17,31,32 Another point to consider is the reversal of these anticoagulant agents. Reversing DOACs using specific reversal therapies in acutely bleeding patients are based on time from last dose, 33 but estimating drug levels may be useful in some indications to determine the need for a reversal.…”

“…In DOACs, there is a chasm between intended use of the drugs with the advertised lack of requiring continuous or episodic monitoring and the reality of needing to measure DOAC levels in acute clinical settings. 14 , 15 , 16 , 17 , 18 , 19 Routine coagulation tests that have historically been useful and successful for assessing anticoagulation, such as the PT and APTT no longer serve as a warning beacon in the age of DOACs as their insensitivity or variable sensitivity to DOAC exposure limits their utility. 20 , 21 , 22 , 23 , 24 Other routine, albeit perhaps less commonly available, coagulation tests available for clinicians would be the thrombin time (TT) or anti‐FXa chromogenic assays.…”

“… 30 Nevertheless, the absence of evidence is not the same as the evidence of a absence and more and more scientific data support the assumption that there is room for improvement in decreasing the number of bleeds (and herewith associated mortality, comorbidity, and health care costs) among patients who are anticoagulated with DOACs. 17 , 31 , 32 …”