View source for Direct oral anticoagulants

<section begin="clinical biochemistry" />'''Direct oral anticoagulants''' (DOACs) are commonly used [[anticoagulants]]. As the name suggests, they act directly on one of the [[clotting factors]] and because they’re taken orally (except argatroban).<section end="clinical biochemistry" />

DOACs are mostly used as safer and non-inferior alternatives to [[warfarin]].

They are also called '''novel oral anticoagulants''' (NOACs), although they were introduced in 2008, so this name is no longer fitting.

== Compounds ==

* Direct thrombin inhibitors
** Dabigatran (Pradaxa®)
** Argatroban
*** (NB! Not taken orally, so not technically a DOAC)
* Direct factor X inhibitors
** Apixaban (Eliquis®)
** Rivaroxaban (Xarelto®)
** Edoxaban (Lixiana®)
* Antidotes
** Idarucizumab (antidote to dabigatran)
** Andexanet (antidote to apixaban and rivaroxaban)

== Indications ==
DOACs can be used for most indications for anticoagulants, including [[stroke]] prevention in [[atrial fibrillation]] and prevention and treatment of [[venous thromboembolism]].

== Mechanism of action ==
These drugs bind to and inhibit certain clotting factors directly. Dabigatran and argatroban bind to and inhibit thrombin (factor IIa). Rivaroxaban, apixaban, edoxaban are factor Xa inhibitors.

Idarucizumab is a monoclonal antibody which binds to and inactivates dabigatran. Andexanet is a modified recombinant factor Xa. Apixaban and rivaroxaban bind to andexanet with the same affinity as factor Xa, which frees up endogenous factor Xa.

== Pharmacokinetics ==
DOACs are excreted renally, and so require dose adjustment in mild forms of kidney failure and possibly being contraindicated in severe forms. Dabigatran is renally excreted to a much larger degree than the factor Xa inhibitors.

However, they’re also metabolised by the liver and so are also contraindicated in severe liver failure.

== Contraindications ==
* Pregnancy
* Mechanical [[prosthetic heart valve]]
* Severe [[kidney failure]]
* Severe [[liver failure]]
* Extremes of body weight (very high or very low)
** Requires dose adjustment in some DOACs and is contraindicated for others

== Reversal ==
Idarucizumab and andexanet can be used to reverse their effect, but are not readily available and are quite expensive. They're mostly reserved for life-threatening haemorrhage. Transfusion of fresh frozen plasma (FFP) can also reverse their effect in theory, but the clinical value of doing this is uncertain.

== Monitoring ==
<section begin="clinical biochemistry" />There is no routine monitoring of DOAC efficacy, as they have a predictable dose-effect relationship. Many labs can measure the serum level of the specific DOAC or the anti-factor Xa assay (a different assay from the one used for UFH/LMWH), but this does not correlate with therapeutic efficacy, only drug absorption. As such, monitoring is rarely indicated.<section end="clinical biochemistry" />

== Advantages of DOACs vs VKAs ==

* Don’t require regular monitoring
* Lower bleeding risk

== Disadvantages of DOACs vs VKAs ==

* Reversing their effect requires antidotes which are very expensive and not readily available
* More expensive

[[Category:Pharmacology]]