Direct Oral anticoagulants ( DOACs ) for the Treatment of Deep Vein Thrombosis ( DVT ) and Pulmonary Embolism ( PE )

Publication: 09/10/2014  
Next review: 20/11/2023  
Clinical Guideline
ID: 3974 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Direct Oral anticoagulants (DOACs) for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Patient Information Leaflet - Confimed Blood Clot (Deep Vein Therombosis and Pulmonary Embolism)

Summary of Guideline

DOACs are licensed for the treatment of acute DVT and PE and the prevention of recurrence. They are approved by the National Institute of Clinical Excellence (NICE) to be offered as an option to patients requiring treatment of an acute DVT or PE and prevention of recurrence.

Adult patients < 120kg diagnosed with a new DVT or PE as per LTHT Venous Thromboembolism (VTE) Treatment Guideline can be considered for a DOAC (see notes below regarding use of rivaroxaban and apixaban for patients 120-150kg).

Note that patients who are unsuitable for warfarin because of contraindications to anticoagulation or major compliance issues are also unsuitable for a DOAC.

The guideline gives details on how to safely anticoagulate with a DOAC including monitoring and follow up.

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To offer patients the most appropriate treatment for their VTE

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Low molecular weight heparin (LMWH) and warfarin have been the mainstay of VTE treatment for many years. In 2012 rivaroxaban was licensed for the treatment of DVT and prevention of recurrence. In 2013 it was licensed for the treatment of PE and prevention of recurrence. NICE Technology Appraisal (TA) 261 and NICE TA287 were published in 2012 and 2013 respectively supporting the use of rivaroxaban as an option for the treatment of VTE. LTHT started using rivaroxaban for VTE treatment in selected patients in 2014. Apixaban, dabigatran and edoxaban have all since been licensed and approved by NICE as options. This guideline aims to help clinicians to decide on an appropriate anticoagulant for their patient with a new VTE including considerations for elderly patients with low body weight or poor renal function and menstruating women who are at risk of heavy menstrual bleeding with anticoagulants, which seems to be more of a problem with once daily options. 

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See LTHT VTE Treatment Guideline.

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See LTHT VTE Treatment Guideline.

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See LTHT VTE Treatment Guideline.

Patients diagnosed with a DVT or PE can be offered a DOAC if all of the following apply

  1. No need for reversible anticoagulant specifically identified i.e. high bleeding risk patients are not suitable for a DOAC
  2. < 120kg (rivaroxaban and apixaban can be considered in patients up to 150kg if appropriate, see below)
  3. No contra-indications to their use, see below
  4. Creatinine clearance > 20ml/minute (Creatinine clearance in trials used actual body weight in patients up to 120kg (use adjusted body weight by adding height into the MDCALC creatinine clearance calculator) if > 120kg or BMI >40).)
  5. LFTs < 2 x upper limit of normal (if only one result out of range may be appropriate to us)
  6. Not on any interacting medications which may reduce or increase levels - see details on drug choice below but the following preclude the use of any DOAC for acute VTE treatment
    rifampicin, carbamazepine, phenytoin, phenobarbitone, st johns wort
    HIV protease inhibitors e.g. ritonavir - check HIV drug interactions website for other HIV drugs and DOACs, azole antifungals (except fluconazole)
  7. Not pregnant or breast-feeding and women of child bearing age must be on adequate contraception (NB this may apply to many young women presenting with VTE who may be advised to stop a COCP. Adequate family planning advice is an important aspect of VTE management in young women). Note also that the once daily DOACs (edoxaban and rivaroxaban) appear to cause heavier menstrual bleeding than apixaban or dabigatran and the later should be considered first line for women where this may be an issue.
  8. No prosthetic (mechanical) heart valve
  9. No diagnosis of anti-phospholipid syndrome

If a DOAC is considered appropriate discuss options with the patient. If they decide to be treated with a DOAC see below for dose and monitoring guidance. Note edoxaban and dabigatran are only licensed after 5 days of low molecular weight heparin (LMWH) has been given.

The guidance for cancer associated thrombosis treatment has been updated to recommend DOACs as first line if appropriate in line with NICE guidance
Diagnosis and Management of Cancer Associated Thrombosis

Choice of DOAC

Rivaroxaban and apixaban can be considered as options for VTE treatment in patients up to 150kg. There is limited data from 120kg to 150kg but rivaroxaban has been the most well studied and does not appear to be affected by weight. Apixaban is also an option. Edoxaban and dabigatran should not be used in patients over 120kg. Over 150kg there is extremely limited data for any of the DOACs for acute VTE treatment
For patients with creatinine clearance 20-30ml/min edoxaban 30mg once a day after an initial 5 days of LMWH can be considered
Edoxaban can also be considered for patients on concomitant cytochrome P450 inducers or inhibitors where apixaban and rivaroxaban are contra-indicated or there is concern - see individual SPCs or discuss with ward pharmacist.
LMWH alone or while initiating warfarin are also options for patients:
on interacting medication, patients
> 150kg,
in need of reversible anticoagulant,
with poor renal or liver function or
patient choice.



For all patients with creatinine clearance > 50mls/minute the starting dose is 15mg twice daily with food for 3 weeks. This should be prescribed in full and supplied from a hospital pharmacy.

Patients should then receive 20mg once a day with food. The importance of taking with food for absorption should be emphasised.

Patients with creatinine clearance 30-50ml/min should receive apixaban or edoxaban.

All patients should have a review at 3 months. For patients requiring long term anticoagulation the dose after 6 months treatment can be continued at the same dose or reduced to 10mg once a day if concerns regarding bleeding risk or low risk of recurrence.

If the patient has already received > 5 days of LMWH consider reducing the number of days of 15mg twice daily given to take into account doses of LMWH given i.e. if 7 doses of LMWH given just give 14 days of rivaroxaban 15mg twice a day before reducing to 20mg once a day.



For patients >50kg with creatinine clearance > 30mls/minute the starting dose is 10mg twice daily for 1 week. Caution is needed regarding this initial dose if elderly, low body weight or frail and edoxaban may be a preferred option. This should be prescribed in full and supplied from a hospital pharmacy.

Due to concerns locally about bleeding risk apixaban is not advised for initial treatment of a VTE in patients <50kg with CrCl < 40ml/min due to the increased exposure seen with the 10mg twice daily dose.

Patients with creatinine clearance > 30ml/min should then receive 5mg twice a day for a maximum of 6 months then, if long -term treatment is required reduce the dose to 2.5mg twice a day after 6 months of full dose. The 5mg twice a day dose is not licensed for long term prevention.

If the patient has already received > 2 days of LMWH and is elderly or frail consider reducing the number of days of 10mg twice daily given to take into account doses of LMWH given i.e. if 3 doses of LMWH given just give 4 days of apixaban 10mg twice a day before reducing to 5mg twice a day.

Apixaban (and dabigatran, see below) appear to cause less heavy menstrual bleeding than edoxaban or rivaroxaban and should be considered first line for women where this may be an issue. 



All patients should receive LMWH treatment dose for 5 days then edoxaban 60mg once a day if creatinine clearance > 50ml/min and weight > 60kg or 30mg once a day if creatinine clearance 20-50ml/min or weight < 60kg. Patients on concomitant ciclosporin, dronedarone, erythromycin or ketoconazole should also receive the 30mg dose.

Do not use for treatment of acute VTE in patients > 120kg.



All patients should receive LMWH treatment dose for 5 days then dabigatran 150mg twice a day. Dabigatran and to some extent apixaban seem to cause less heavy menstrual bleeding than rivaroxaban and edoxaban and may be considered in women of child bearing age who may be affected.

Do not use for treatment of acute VTE in patients > 120kg.

Ensure patients have had full blood count (FBC), urea and electrolytes (U&E), liver function tests (LFTs) and baseline clotting checked prior to commencing anticoagulation. If a patient is already on anticoagulation and a new VTE is suspected please also take an appropriate drug level if a DOACor anti facor Xa level if LMWH. Please note the time of the last dose of anticoagulant

Give patients written information on their anticoagulant in the form of the LTHT or  pharmaceutical company leaflet on DVT or PE.

Ensure they have an anticoagulant alert card (these are found in the boxes of medication)

The DOAC counseling checklist in the clinical documents section of PPM+ should be used to ensure appropriate counseling is given to patients and as a legal document to confirm the information has been provided.


 Today --------Patients name------ has been commenced on a DOAC (Direct Oral Anticoagulation) following their diagnosis of DVT/PE and an information booklet, patient alert card and initial prescription has been provided.

The following points have been discussed with your patient.

Indication for DOAC                                                                                                                           

Suitable renal function with Creatinine Clearance >30ml/min for Apixaban                     

Suitable renal function with Creatinine Clearance >50ml/min for Rivaroxaban                                             

Suitable hepatic function                                                                                                      

How the chosen DOAC works, factor Xa inhibitor, oral medication approach, no routine

coagulation monitoring                                                                                                                                      

The lack of an antidote                                                                                                                        

The increased risk of bleeding whilst taking an anticoagulant

What to do if bleeding occurs

                            -trivial bleeding/unexplained bruising - Consult GP

                            -major bleeding - Proceed to A&E immediately                                                    

A review of current medication to ensure no interactions                                     

Advice to avoid aspirin or NSAIDs unless prescribed intentionally                                   

If applicable, has had a negative pregnancy test prior to commencing the DOAC                           

An explanation of risks of pregnancy/contraceptive advice has been discussed                                             

The importance of taking with food if prescribed Rivaroxaban                                          

The impact of alcohol while on a DOAC                                                               

The possible side effects                                                                                                       

An explanation of what to do if doses are missed                                                  

How they intend to manage their dosing                                                                

The planned dose change at 1 or 3 week depending on DOAC chosen                 

Advice to inform Healthcare Professional (Dentists etc)                                                                  

Instructions have been given on the initial starting dose and the on-going maintenance

dose along with a review appointment time and date                                                           



Provide every patient with a follow-up plan, patient information leaflet and, at discharge, a discharge letter which should include:
i. The likely cause of the DVT or PE
ii. Whether it was provoked or unprovoked
iii. Details of follow-up appointment(s)
iv. Any further investigations required
v. Details of anticoagulant prescribed and its duration, in line with NICE CG144

If the patient is an oncology patient still under active care by the oncology team they should be sent a copy of the eDAN with clear documentation for them to follow up regarding anticoagulation.



For patients suitable for ambulatory treatment that have been assessed on SDEC or would have otherwise followed the ambulatory pathway

  1. reviewed within 48 hours by a senior member of the medical team or senior advanced clinical practitioner on SDEC.
  2. reviewed at 1 or 3 weeks (to coincide with the dose change of the DOAC) to discuss dose change and adherence, side effects and follow up for any other investigations as per LTHT VTE treatment guideline. Also occurs on SDEC. The patient will be given 1 month of treatment by SDEC.


The GP should be approached at this stage to take over prescribing of the DOAC.

All patients should be reviewed at 3 months to consider continuation of anticoagulation if appropriate on SDEC by a senior ACP, thrombosis clinic for patients who have had their VTE and been hospitalized or whilst in hospital or Respiratory Clinic in the case of PE

For patients who would not have been accepted on the ambulatory pathway the initiating team need to ensure they are counseled as above and the patient is aware of the change in dose, if not already done, and a review appointment should be made if appropriate. Patients should be reminded they will need further supplies of anticoagulation from their GP. All patients should be referred to the thrombosis team using the referral form on the VTE pages of the clinical guidelines section on the intranet.  They will arrange 3 or 6 month follow up as clinically appropriate with either thrombosis team or respiratory team.

Treatment durations

Proximal DVT or PE

Assess and discuss the benefits and risks of continuing, stopping or changing the anticoagulant with people who have had anticoagulation treatment for 3 months (3 to 6 months for people with active cancer)

-       Provoked event - consider stopping anticoagulation treatment at 3 months (3 to 6 months for people with active cancer) if the provoking factor is no longer present and the clinical course has been uncomplicated. If anticoagulation treatment is stopped, give advice about the risk of recurrence and provide:

  • written information on symptoms and signs to look out for
  • direct contact details of a healthcare professional or team with expertise in thrombosis who can discuss any new symptoms or signs, or other concerns
  • information about out-of-hours services they can contact when their healthcare team is not available

 -   Unprovoked event - consider continuing anticoagulation beyond 3 months (6 months for people with active cancer). Base the decision on the balance between the person's risk of venous thromboembolism (VTE) recurrence and their risk of bleeding. Discuss the risks and benefits of long-term anticoagulation with the person, and take their preferences into account.

  • Explain to people with unprovoked DVT or PE and a low bleeding risk that the benefits of continuing anticoagulation treatment are likely to outweigh the risks.
  • Do not rely solely on predictive risk tools to assess the need for long-term anticoagulation treatment.
  • Consider using the HAS-BLED score for major bleeding risk to assess the risk of major bleeding in people having anticoagulation treatment for unprovoked proximal DVT or PE. Discuss stopping anticoagulation if the HAS-BLED score is 4 or more and cannot be modified.

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Record: 3974

To provide evidence-based recommendations for appropriate treatment of VTE.

Clinical condition:


Target patient group: Patients with an acute VTE
Target professional group(s): Secondary Care Doctors
Secondary Care Nurses
Adapted from:

Evidence base

References  and Evidence levels:


NICE TA261, 287, 341, 354

  • Use of direct oral anticoagulants in patients with obesity for treatment and prevention of venous thromboembolism: Updated communication from the ISTH SSC Subcommittee on Control of Anticoagulation

Karlyn A. Martin, et al 14 July 2021, Journal of thrombosis and haemostasis

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs

B. Robust experimental or observational studies

C. Expert consensus.

D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 3.0

Related information

Not supplied

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