In the last decade, five direct oral anticoagulants (DOACs) have made their way to the clinic, but clinicians may encounter challenging patient scenarios for which there is little evidence to guide their use or the management of complications. In “DOACs in the Real World,” experts will tackle several of these issues, from appropriate dosing to minimizing bleeding risk. Here, session chair Ravindra Sarode, MD, previews the topics panelists will discuss.
DOACs are a hot topic in nonmalignant hematology. What aspects of their use will be discussed in this session?
These agents are increasingly being used in clinical practice for the treatment and prophylaxis of venous thromboembolic conditions. They have several advantages over conventional vitamin K antagonist (VKA) therapy because they do not require routine laboratory monitoring, generally do not interact with foods or other drugs, and have a significantly lower risk of intracranial hemorrhages.
Still, because these drugs are relatively new and there are now five options, instead of just one VKA – warfarin – there are many unknowns that we are encountering in daily practice. Clinical trials of DOACs excluded many patients, such as children, people at extremes of body weight, those on DOACs undergoing urgent or emergent surgeries, people with clinical conditions not studied during trials, and patients who present with major bleeding.
In this session, Beverley Hunt, OBE, FRCP, FRCPath, will discuss the role of low-dose DOACs as prophylaxis to avoid bleeding risk, while Deborah Siegal, MD, will cover the reversal of DOACs – another pressing issue.
Because DOACs remove the need for close monitoring, what information do clinicians use to guide treatment?
One of the major advantages of DOACs is that they don’t require routine laboratory monitoring, as with warfarin, and patients do just fine. Still, there are several clinical circumstances where we may want to know the drug effect or actual drug level, including for patients who have not responded to prior therapy. Unfortunately, routine coagulation tests are not useful in assessing DOAC effects or levels and there are no approved rapid assays that can be used to measure these levels. This has become more relevant as the first specific reversal agents for DOACs, andexanet alfa and idarucizumab, were approved in 2018.
What are the benefits – and limitations – of these reversal agents?
Idarucizumab and andexanet alfa are specific reversal agents, and are useful in patients who present with major bleeding while taking DOACs. However, since all DOACs have short half-lives, the lack of rapid assays limits our ability to use these reversal agents judiciously. This is particularly true for andexanet alfa, a factor Xa inhibitor, because it is expensive and is known to have some prothrombotic properties due to its inhibition of tissue factor pathway inhibitor.
It is obligatory to measure the factor Xa inhibitor level before giving an expensive drug that can potentially be thrombogenic in a patient with an underlying prothrombotic state.