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

Publication: 09/10/2014  --
Last review: 20/11/2019  
Next review: 20/11/2022  
Clinical Guideline
ID: 3974 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2019  


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.

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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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. Dabigatran is not included in the guideline as is not felt to have a place in the acute management of VTE at LTHT


See LTHT VTE Treatment Guideline.


See LTHT VTE Treatment Guideline.

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Treatment / Management

See LTHT VTE Treatment Guideline.
Patients diagnosed with a DVT or PE can be offered a DOAC if any of the following apply

  1. No need for reversible anticoagulant i.e. high bleeding risk patients are not suitable for a DOAC

  2. < 120kg (little evidence in patients above this weight)

  3. No contra-indications to their use

  4. Creatinine clearance > 20ml/minute (Creatinine clearance in trials used actual body weight.)

  5. LFTs < 2 x upper limit of normal

  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 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. No active cancer (see oncology guideline)

  8. 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).

  9. No prosthetic (metallic) heart valve

  10. 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 is only licensed after 5 days of low molecular weight heparin (LMWH) has been given.

Choice of DOAC
Rivaroxaban and apixaban can be offered as first line options for 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, > 120kg, in need of reversible anticoagulant, poor renal or liver function or on 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.
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.

For all patients with creatinine clearance > 30mls/minute the starting dose is 10mg twice daily for 1 week. This should be prescribed in full and supplied from a hospital pharmacy.
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

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, ketoconazole should also receive the 30mg dose.

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.

Give patients written information on their anticoagulant in the form of the pharmaceutical company leaflet on DVT or PE.
Ensure they have an anticoagulant alert card (these are found in the boxes of tablets)


The DOAC counseling checklist should be used to ensure appropriate counseling is given to patients and as a legal document to confirm the information has been provided. (Currently being adapted for PPM)

 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                                                                 


For patients suitable for ambulatory treatment that have been assessed on JAMA 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 JAMA.
  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 JAMA by a senior advanced clinical practitioner. The patient will be given 1 month of treatment by JAMA.

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 JAMA by a senior ACP in the case of DVT and 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 counselled 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. Further follow up at 3 months to assess the course length is also required. For any patient with a PE please refer to the respiratory team for review.

Treatment durations
Clearly provoked 1st DVT                            3 months
or provoked 1st PE with reversible
risk factor      
Sub massive/Massive provoked PE         6 months minimum/consider long term

For all others: assess the risk of recurrence versus risk of bleeding at 3 months
Unprovoked 1st distal DVT                         6 months

Unprovoked PE                                         Lifelong anticoagulation unless                                        
                                                                  the risk of bleeding is increased

Unprovoked proximal DVT                       Consider extending anticoagulation                                     beyond 3 months and discuss pros and cons of lifelong anticoagulation with the patient at 3 months. If there are persistent identifiable risk factors for recurrence and a low risk of bleeding, lifelong anticoagulation is the appropriate choice. If there is a significantly increased risk of bleeding stop treatment at 3 months. Individual risk assessment is necessary.           

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Record: 3974


To offer patients the most appropriate treatment for their VTE


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

NICE TA261, 287, 341, 354
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 2.0

Related information

Not supplied

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