For new doctors, prescribing anticoagulants can be daunting. A few simple rules can make this easier. Ensure you use your local guidelines in the first instance, which often provides information on first-line agents and dosing. The information below may be incorrect and so hence, as per our disclaimer, do use your own clinical judgement.
The anticoagulation agents
- Low molecular weight heparin (LMWH)
- Adjusted by weight & renal function
- Short duration of action
- Cheap, easy to reverse & but requires regular INR checks
- Long duration of action (about 5 days to completely reverse)
- Other Vitamin K antagonists are rarer
- Direct Oral Anticoagulants (DOACs)
- Formerly known as NOACs
- Includes apixaban, rivaroxaban, dabigatran, edoxaban
- May require adjusting by weight, age & renal function
- Advantage of not requiring INR checks but they don’t have as wide a license as the above two & have essentially no reversal agent (except dabigatran)
- Medium duration of action (a few days of cessation before reversal)
- Similar to heparin
Common scenarios you may encounter include
- A patient newly needs to start (or restart) anticoagulation for atrial fibrillation or a venous thromboembolic event (VTE: DVT or pulmonary embolism)
- A patient needs to transition between anticoagulation (possibly due to requiring surgery or other procedures)
- A patient needs their warfarin prescribed for continued dosing based on their INR (and what to do if the patient is bleeding)
Scenario 1: Newly starting (or restarting) anticoagulation
The decision to start or restart anticoagulation should be senior-led. To select the right agent, consider factors impacting the patient and their relative as well as counselling them on risks and benefits. Do take into account the risk of bleeding (e.g. HAS-BLED score). Do note though that the HAS-BLED score is not validated in VTE.
Indications might include
- Atrial fibrillation (AF)
Duration for VTE
- For VTE, usually at least 3 months by when they will have usually seen a haematologist in a clinic for review of total duration. Often for a DVT with transient risk factors, anticoagulation may be stopped within 12 months (often 6 months). Duration should be senior-led.
- There are lots of reasons why indefinite anticoagulation may be considered e.g. unprovoked DVT, provoked with ongoing risk or recurrent DVTs
- This needs to be balanced against high bleeding risk (where discussion with seniors or haematology is advised)
Patients are started on either treatment dose LMWH or a DOAC
- Use LMWH when
- Contraindications for DOACs exist such as pregnancy, anticipated need for discontinuation/reversal & malignancy
- If there’s extensive clot burden or if the patient is haemodynamically unstable
- If it will take time to obtain the DOAC
- You may need to use unfractionated heparin in severe renal failure
- Consider fondaparinux in patients with heparin-induced thrombocytopenia
- Use DOACs for their ease & avoidance of injections
- Rivaroxaban & Apixaban are licensed as monotherapy i.e. do not require LMWH bridging
- Use the BNF & local guidelines for dosing regimes
Patients newly starting on anticoagulation are usually seen in the anticoagulation clinic. The pharmacist will usually counsel them & give them an anticoagulation book. Here are some of the information to give for Warfarin and DOACs.
- Importance of testing INR in warfarin & impact of diet and acute illness on INR
- Seeking medical attention if bleeding occurs
- Being cautious with NSAIDs
- Key drug interactions
- Decisions regarding when to stop anticoagulation before surgery should be senior-led as it requires a balance of thrombotic risk & bleeding risk. This also guides whether bridging should be required.
- For a raised INR due to warfarin, do not give prothrombin complex concentrate for non-emergency operations. Instead, try to delay the operation following administration of 5mg intravenous vitamin K
- Typically depending on the risks above, Warfarin is held for 5 days and DOACs are held for 48 hours
- DOACs or post-operative LMWH bridging for warfarin are usually then restarted after 48 hours (earlier in low-risk procedures)
- Read the guidelines from the British Society of Haematology for more information
Scenario 2: Transitioning between anticoagulation
Have a low threshold to discuss with seniors and haematology if the patient has a high risk of bleeding or thrombosis. Here we talk only about patients with a target of INR 2.5 (2-3). Usually, DOACs are preferred unless there’s contraindications or particular reasons why warfarin would be preferred (see Scenario 1). This is due to the following factors
- Warfarin requires regular visits for INR monitoring (although conversely, it is hard to detect non-compliance with DOACs)
- Patients on warfarin often spend a substantial amount of time out of range
- Diet and other medications can radically affect warfarin
- Other contraindications to Warfarin e.g. pregnancy
- Patients are often bridged with LMWH for 5 days & until the INR is within the therapeutic range for 2 consecutive days (at which point the LMWH can be stopped)
- For AF if they have a high CHADVASC score then bridging is often used
- Those with recent (less than 3 months) embolic stroke or VTE are often bridged
- Those with mechanical valves or recent coronary stenting are often bridged
- If they are newly starting warfarin
- Ensure you’ve reviewed their baseline INR, LFTs, U&Es and excluded pregnancy
- Consider the dosing regime below
- For patient usually on warfarin, their usual dose is simply restarted
- It takes about 2 days for the INR to start to increase. Also repeated dosing may take 2 days to have an effect, therefore, don’t make lots of changes to warfarin dosing daily.
- Once the patient is established on warfarin & is due to be discharged, ensure they have an INR check due within a few days
- This can be difficult, particularly because the direct Xa inhibitors (“-xaban”) prolong the INR making interpretation difficult
- Often it is easier to switch from DOAC to LMWH then use the above
- Simply start LMWH/DOAC once the INR becomes subtherapeutic i.e. INR below 2
- Simply start the other at the next administration time
- If on a BD LMWH regime, start the DOAC at 6-12h post last LMWH dose
- If on an OD LMWH regime, start the DOAC 12-24h post last dose of LMWH
Scenario 3: Prescribe this patient’s warfarin
You are frequently required to chase an INR and dose warfarin accordingly. Generally, the accepted dose range is 0.5 above or below the target INR.
If the patient is bleeding
- In major bleeding (i.e. life or limb-threatening where reversal is required within 6-8h) discuss with seniors for consideration of prothrombin complex concentrate. Intravenous 5mg Vitamin K should be given but will take 6-8h to have an effect. Fresh frozen plasma is less effective.
- In non-major bleeding 1-3mg of intravenous Vitamin K should be used (oral is slow acting)
- Note that if the INR is within therapeutic range then bleeding should be investigated e.g. haematuria for renal cancer
- If the INR is above 8 then oral 1-5mg Vitamin K can be used. Expect reversal within 24 hours, so if the INR is still raised then give another dose.
- If the INR is above 5 but below 8, then hold the warfarin for 1-2 doses and review the maintenance dose. Ensure you investigate the underlying cause of the raised INR.
- Maintaining INR within the therapeutic range is an art rather than a science
- Continue current dosing regime if the INR is within range otherwise make 1-2mg adjustments and monitor for at least 2 days before making further changes
- Remember in high-risk patients you can always give bridging LMWH.
- Guidelines on Warfarin
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