Authors: Jasmine Medhora / Editor: Liz Herrieven / Codes: / Published: 29/11/2022
Patients who are taking an oral anticoagulant present to the Emergency Department (ED) fairly frequently. Common reasons for being prescribed an anticoagulant include atrial fibrillation, a mechanical heart valve or previous pulmonary embolism. Anticoagulants impact upon presenting complaint to the ED, for example, with a head injury, trauma or a gastrointestinal bleed. Another group of patients where anticoagulant reversal may be considered is in those who have taken an oral anticoagulant overdose. Deciding whether or not to reverse anticoagulation in these situations is a key part of emergency management.
Ultimately, as with most decisions in medicine, the decision to reverse anticoagulation depends on the risk versus the benefit of doing so for that individual patient. There are a few things to consider in particular when weighing up the two sides:
> Which agent is the patient on and why?
Patients on anticoagulation for indications such as atrial fibrillation are potentially at less risk if their anticoagulant is stopped or reversed acutely compared to patients who have a mechanical heart valve, for example.
> When did they last take it?
It is useful to find out what dose of anticoagulant the patient is on and when they last took it. Depending on the half-life of the drug, you may be able to avoid actively reversing it.
> Are there any other factors affecting the patients clotting?
This could include other medications such as anti-platelet therapy or medical conditions such as liver cirrhosis or thrombocytopenia.
Also, remember that renal or hepatic dysfunction can affect the clearance of oral anticoagulants and therefore prolong their effect.
> Is reversal required?
The main question here is: does the patient have major bleeding? Think about the patient’s clinical presentation and assess whether they are haemodynamically stable.
A major bleed can be defined as a patient having at least one of the following:
- haemodynamic instability
- bleeding at a critical site
- overt bleeding with a drop in haemoglobin of two units or more
- requirement of red blood cell transfusion of two units or more
Haemodynamic instability is commonly defined as a systolic blood pressure <90mmHg and tachycardia. However, consider the patient in front of you as they may not fit these exact criteria. Look for a falling trend in their systolic blood pressure, postural drop and signs of poor end organ perfusion such as confusion or reduced urine output.
Critical site bleeds are those that compromise organ function or can lead to severe disability and require surgical control of bleeding. These sites include intracranial, intraocular, intra-abdominal and intra-articular sites. The gastrointestinal tract is not considered to be a critical site but bleeding here (frequently seen in the Emergency Department) does cause haemodynamic instability and, therefore, can be a cause of a major bleed.
If initial measures to manage major bleeding are not working, reversal of anticoagulation is indicated.
> Which drug is required for reversal and how much is needed?
Drugs for reversing novel anticoagulants are expensive and may be in limited supply in the hospital. Ensure your dose calculation is correct and contact the on-call pharmacist sooner rather than later if there are issues in sourcing enough of the drug.
Some of these drugs take a little while to draw up! Factor this into your management plan and ensure other stabilizing measures such as volume resuscitation with good IV access and local compression are ongoing.
Consider whether discussion with the on-call haematologist is indicated. The hospital you work in may require a discussion with haematology to release certain products from the blood bank but, also, the haematology team will be able to offer expert advice specific to your patients situation.
Warfarin vs DOACs
Warfarin
The half-life of warfarin is 5-7 days. Find out when the patient last had their warfarin.
Measure the patients INR at baseline.
If the patient presents with intracranial haemorrhage, do not wait for the INR result, give prothrombin concentrate.
In all other cases with major bleeding. requiring reversal, use 10mg vitamin K IV. Vitamin K takes 6-12 hours to work therefore must be given alongside another method of reversal. If prothrombin concentrate is not available, then use 4 units of FFP. This will work for 8 hours whilst vitamin K begins to work.
Measure the efficacy of reversal by checking the INR. In the case of intracranial haemorrhage this should be every 3-6 hours.
Direct Oral Anticoagulants
Apixaban
A direct Xa inhibitor with a half-life of 6.8-15.2 hours.
Rivaroxaban
A direct Xa inhibitor with a half-life of 5-11.7 hours.
The approved reversal agent for apixaban and rivaroxaban is Andexanet Alfa. It reversibly binds to the drug and inactivates it. NICE guidance states that Andexanet Alfa should only be used for reversal when there is uncontrolled or life-threatening bleeding in the gastrointestinal tract. This is based on evidence showing that it is likely to reduce 30-day mortality for patients with gastrointestinal bleeding. The evidence is unclear as to whether this reversal agent reduces mortality in intracranial haemorrhage.
Dosing can be low dose or high dose depending on when the patient last took rivaroxaban or apixaban and how much they took.
Low dose: 400mg IV bolus at 30mg/min followed by continuous infusion of 480mg at 4mg/min
High dose: 800mg IV bolus at 30mg/min followed by continuous infusion of 960mg at 8mg/min
If Andexanet Alfa is not available, prothrombin concentrate is recommended.
Dabigatran
A direct thrombin inhibitor with a half-life of 12-17 hours.
The approved reversal agent for dabigatran is Idarucizumab which irreversibly binds to the drug and inactivates it. This drug is approved for reversal of dabigatran for emergency surgery or urgent procedures or in life-threatening bleeding.
The recommended dose is 5g IV as 2 consecutive infusions over 5-10 minutes or as 2 bolus injections of 2.5g. A further 5g dose can be given if indicated.
If Idarucizumab is not available, prothrombin concentrate is recommended
Edoxaban
A direct Xa inhibitor
There is no licensed reversal agent for Edoxaban. Prothrombin concentrate is recommended if reversal required.
This blog has focused on reversal of DOACs and warfarin. Don’t forget protamine for reversal of heparin, including LMWH & fondaparinux. Anticoagulant reversal should always be considered alongside measures to stop the bleeding and consideration of tranexamic acid, blood products and perhaps haematology support.
References
- Farkas J. Anticoagulant reversal. The Internet Book of Critical Care (IBCC). 2021.
- Baugh CW, Levine M, Cornutt D, et al. Anticoagulant Reversal Strategies in the Emergency Department Setting: Recommendations of a Multidisciplinary Expert Panel. Ann Emerg Med. 2020 Oct;76(4):470-485. doi: 10.1016/j.annemergmed.2019.09.001.
- Tomaselli G, Mahaffey K, Cuker A, et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. J Am Coll Cardiol. 2020 Aug, 76 (5) 594622.
- National Institute for Health and Care Excellence. Andexanet alfa for reversing anticoagulation from apixaban or rivaroxaban. NICE Technology appraisal guidance [TA697]. May 2021.
- Ondexxya Summary of Product Characteristics. European Medicines Agency.