Anticoagulation and antiplatelet management, pleural disease investigation and treatment (637)

Warning

1. Abbreviations

AF

Atrial Fibrillation

DAPT

Dual Antiplatelet Therapy

DOAC

Direct Acting Oral Anticoagulant

eGFR

Estimated Glomerular Filtration Rate

NHS GGC

NHS Greater Glasgow & Clyde

ICA

Intercostal Artery

ICD

Intercostal Chest Drain

INR

International Normalised Ratio

IPC

Indwelling Pleural Catheter 

LAT

Local Anaesthetic Thoracoscopy

LMWH

Low Molecular Weight Heparin

TIA

Transient Ischaemic Attack

2. Background and scope

2.1    Introduction

The investigation and treatment of pleural disease is characterised by invasive sampling and drainage procedures including thoracentesis, intercostal chest drain (ICD) insertion, indwelling pleural catheter (IPC) insertion and local anaesthetic thoracoscopy (LAT). Each are associated with a degree of haemorrhagic risk, with the most frequently-occurring serious example being blood loss secondary to intercostal artery (ICA) trauma. Significant morbidity, and even mortality, arising from ICA injury is well described and may occur even where diagnostic pleural sampling with a 21G needle is performed. 1 

Historic retrospective studies report rates of haemorrhagic complication in the order of 2% for thoracentesis and up to 13% for ICD insertion, although these were recorded before the widespread availability of point-of-care thoracic ultrasound. 2 Appropriate operator experience and use of image guidance are recognised to significantly reduce the risk of procedural complications including bleeding. 3 A trend towards limiting pleural interventions to appropriately trained respiratory physicians is likely to have had a positive effect in this regard. For example, a recent prospective study identified a haemorrhagic complication rate of only 0.18% of 9320 thoracentesis procedures performed by a single highly experienced operator using bedside ultrasound. 4

Nonetheless, despite a low absolute risk of bleeding in experienced hands, the consequences of vascular trauma are likely to be greater where the patient has an impaired haemostatic capacity due to antiplatelet or anticoagulant administration. British Thoracic Society and existing local guidelines therefore state that patients should have an International Normalised Ratio (INR) < 1.5 prior to any non-urgent pleural intervention. 3 However, these guidelines do not stipulate how this should be achieved while avoiding excessive thrombotic risk to individual patients. Furthermore, the use of antiplatelet, and the more recently available and increasingly common direct acting oral anticoagulant (DOAC) medications, are not covered in these guidelines.

 

2.2    Need for Pleural Specific Guidance

In contrast to an isolated surgical procedure, for which specific NHS GGC anticoagulation guidance exists, pleural disease investigation and definitive treatment frequently involves at least 2 separate procedures over a 2 to 3-week interval. For instance, patients with suspected pleural malignancy often undergo initial thoracentesis for diagnostic and immediate therapeutic purposes, followed by either ICD insertion and talc slurry pleurodesis where pleural malignancy is confirmed, or diagnostic LAT to perform pleural biopsies where cytology has been non-diagnostic. Existing perioperative anticoagulation guidance is therefore of limited relevance in this situation where separate procedures are clustered within a short timeframe. 

 

2.3    Scope of Guideline

This guideline refers to the peri-procedural administration of oral anticoagulants,

(warfarin and DOACs) and antiplatelets, including aspirin and ‘potent antiplatelets’

(clopidogrel, ticagrelor, prasugrel), in patients undergoing invasive pleural procedures (thoracentesis, ICD or IPC insertion, LAT). It is intended to be used by respiratory physicians, trainees and clinical nurse specialists who are involved in the care of patients with pleural disease. It will also be relevant to clinicians referring patients with suspected pleural disease to respiratory medicine and thoracic surgery, but these cases should be discussed with the relevant team. 

This document does not provide exhaustive advice and focusses on patients undergoing elective rather than emergency procedures. The guidelines apply to both inpatients and outpatients. In all patients, the urgency of the investigations should be considered when considering these guidelines. In inpatients in particular, there may sometimes be the clinical need to accept a higher risk of bleeding. Although likely to be associated with differing risk profiles, the same advice is offered for each type of pleural procedure which are referred to collectively. 

 

The following patient groups are not covered in this guidance:

  • Patients with endogenous coagulopathy
  • Trauma patients

2.4    Evidence Base

Limited evidence specific to pleural procedures exists on this subject. A systematic literature review has not been undertaken but these guidelines have been based on related national 3,5 and local evidence-based guidelines 6, and expert consensus garnered from respiratory physicians in the West of Scotland Pleural Governance Group and members of the NHS Greater Glasgow & Clyde Thrombosis Committee.

 

2.5    Financial and Resource Implications

Implementation of these guidelines is expected to have minimal impact on organisational running costs. The greatest increased use of resources is likely to arise from additional district nurse visits to provide bridging LMWH injections in previously warfarinised patients embarking on multiple pleural procedures. In many cases, healthcare costs will be minimised as patients, or their relatives, can be quickly trained to safely administer LMWH. Furthermore, the increasing use of DOACs means fewer patients will fall into this category.

Ultimately, it is hoped that these guidelines will facilitate consistent practice based upon the best available evidence in this area and in doing so reduce the frequency of haemorrhagic and thrombotic complications and their significant clinical and financial implications.

 

2.6    Implementation and Evaluation

These guidelines will be disseminated to relevant practitioners via established clinical networks. Adherence to key recommendations summarised in section 4 will be recorded and evaluated within the NHS GGC annual chest drain audit process.

3. Summary of key recommendations

Warfarin (see flowchart in appendix 2)                    

  • Patients should have an INR <1.5 prior to any non-urgent pleural intervention
  • Assess thrombotic risk (see section 4.1)
  • Suspected non-malignant etiology, isolated procedure likely – follow the

Management Plan for Warfarin Patients in the Peri-operative Period included in the Therapeutics Handbook 

  • Suspected pleural malignancy, multiple procedures likely:

Low thrombotic risk: 

  • Stop warfarin 5 days before first pleural procedure
  • Check INR pre-procedure to ensure it is < 1.5
  • Assuming no bleeding complication, start daily bridging enoxaparin 5mg/kg od from 6pm on the day following first pleural intervention
  • Withhold enoxaparin for at least 36 hours prior to subsequent pleural procedures

High thrombotic risk: 

  • Stop warfarin 5 days before first pleural procedure (day -5)
  • Arrange administration of enoxaparin 5mg/kg od around 6pm on days -3 and -2
  • Check INR on day -1. If > 1.4 then 1mg IV Vitamin K should be given
  • Recheck INR on day 0, if not already < 1.5
  • Perform procedure if at least 36 hours since last enoxaparin dose and INR < 1.5
  • Assuming no bleeding complication, administer enoxaparin 40mg at least 4 hours after procedure
  • Restart enoxaparin 5mg/kg od from 6pm on the day following first pleural procedure
  • Withhold enoxaparin for at least 36 hours prior to subsequent pleural procedures

Direct Acting Oral Anticoagulants 

  • DOACs should be withheld for a period of 48 hours prior to elective pleural procedures
  • In patients with high thrombotic risk, a single bridging dose of enoxaparin 1mg/kg may be considered up to 24 hours prior to an elective pleural procedure
  • DOACs can be restarted 18-24 hours following pleural procedure i.e. the following morning

Aspirin

  • Aspirin cessation is not required prior to pleural procedures

Potent Antiplatelet Agents 

  • Elective pleural procedures should not be performed in patients who have received potent antiplatelets (clopidogrel, ticagrelor, prasugrel) within the preceding 7 days
  • Consider deferring procedure until potent antiplatelet no longer indicated if this is likely to occur within a clinically-acceptable timescale
  • Where long term potent antiplatelet therapy indicated, pleural intervention should be deferred until at least 5 weeks following an acute ischaemic event (to allow 4 weeks of uninterrupted antiplatelet treatment).

Where DAPT is planned for greater than 4 weeks, discuss risk/benefit of stopping DAPT early with cardiologist

4. Anticoagulants

4.1    Warfarin

  • Patients should have an INR <1.5 prior to any non-urgent pleural intervention

 

To facilitate this recommendation without undue thrombotic risk, the number of consecutive pleural procedures likely to be required should be considered. Patients referred for pleural investigation fall into 2 main groups: (1) Suspected non-malignant underlying etiology requiring a single pleural procedure to confirm diagnosis (e.g. suspected heart failure), and (2) Suspected pleural malignancy which is likely to require two or more pleural procedures to complete management pathway (typically thoracentesis followed by either LAT or ICD/IPC insertion).

 

Additionally, the degree of thrombotic risk must be considered and the following groupings are suggested: 

 

  • Low thrombotic risk: Atrial Fibrillation (noting high risk exceptions below), venous thrombosis > 3 months previously

 

  • High thrombotic risk:
    • AF within 3 months of stroke/TIA or in combination with any prosthetic heart valve
    • Mechanical heart valve
    • Venous thrombosis within previous 3 months or with known high risk thrombophilia, or prior recurrent venous thrombosis with target INR

3.5

 

4.1.1    Single procedure expected

  • For those patients likely to require a single procedure, their anticoagulation management is analogous to patients requiring elective surgical procedures and the relevant NHS GGC guidance within the Adult Therapeutics Handbook7 should be followed

 

In patients with low thrombotic risk (i.e. most patients with AF) this will simply involve omission of warfarin 5 days prior to intervention and an INR check prior to the procedure. Assuming no bleeding complications, the patient will be able to restart warfarin at their usual dose the same day as the procedure. 

 

Patients with high thrombotic risk will need Low Molecular Weight Heparin (LMWH) bridging as described in the Management Plan for Warfarin Patients in the Perioperative Period included in the Therapeutics Handbook.

 

4.1.2    Multiple procedures expected

For those entering a longer pleural pathway, the situation is clearly more complex since two pleural interventions are likely to fall within 7 – 21 days of each other. This is an inadequate length of time to satisfactorily re-load with warfarin before it needs to be stopped again, but clearly longer than is desirable to leave patients without anticoagulation even where their absolute thrombotic risk is low. There is no role for aspirin in the prevention of embolic stroke or VTE as a temporary substitute for anticoagulation. 8

 

The following recommendations are therefore made for warfarinised patients likely to require a second pleural procedure within the following 21 days:

 

  • Low thrombotic risk:
    • Stop warfarin 5 days before first pleural procedure
    • Check INR pre-procedure to ensure it is < 1.5
    • Assuming no bleeding complication, start daily bridging enoxaparin

1.5mg/kg od from 6pm on the day following first pleural intervention

  • Withhold enoxaparin for at least 36 hours prior to subsequent pleural procedures

 

  • High thrombotic risk:
    • Stop warfarin 5 days before first pleural procedure (day -5)
    • Arrange administration of enoxaparin 5mg/kg od around 6pm on days -3 and -2
    • Check INR on day -1. If > 1.4 then 1mg IV Vitamin K should be given
    • Recheck INR on day 0, if not already < 1.5
    • Perform procedure once at least 36 hours since last enoxaparin dose and INR < 1.5
    • Assuming no bleeding complication, administer enoxaparin 40mg at least 4 hours after procedure
    • Restart enoxaparin at full treatment dose of 5mg/kg od from 6pm on the day following first pleural procedure
    • Withhold enoxaparin for at least 36 hours prior to subsequent pleural procedures

 

To facilitate these recommendations in ambulatory patients, the preferred option is for the patient or family-member to administer the LMWH, with appropriate training provided by the hospital nursing staff. Where this is not possible, close liaison with the community/district nursing team to arrange administration of LMWH would be required. Prescription of LMWH should be arranged via the hospital pharmacy or GP. LMWH should be withheld prior to the next pleural procedure as above; these instructions should be made clear to the patient during their clinic review and supported by written guidance.  

4.2    Direct-acting Oral Anticoagulants

Apixaban, Edoxaban, Rivaroxaban and Dabigatran are the currently available DOACs. In most cases, these agents will be prescribed to prevent embolic stroke in non-valvular AF or for the treatment (and/or prevention) of venous thrombosis. In contrast to warfarin, DOACs have a predictable anticoagulant effect and a shorter half-life (8-13 hours) in patients with normal renal function. 5 

 

Considering these factors, and the typically lower risk indications for DOACs, an acceptable risk/benefit ratio in most cases will be achieved by simply withholding the medication prior to a planned procedure. However, some patients will be taking a DOAC for a high thrombotic risk indication (the most obvious example in current practice would be an acute thromboembolism) and an assessment of thrombotic risk (as described in section 4.1) is recommended.

 

Evidence on the optimal timing of DOAC cessation prior to interventions with bleeding risk is limited however for patients with normal renal function. The British Society of Haematology recommend timing of cessation based on the bleeding risk of the procedure involved; 24 hours prior to a ‘low bleeding risk’ procedure and 48 hours prior to a ‘high bleeding risk’ procedure. 5

 

Given the serious potential consequences of an intercostal artery injury in patients with a residual anticoagulant effect, it is suggested that elective pleural interventions are treated as being of ‘high bleeding risk’ based on the potential severity of this complication rather than likelihood of it occurring. 

 

Low thrombotic risk:

  • DOACs prescribed for low thrombotic risk indications should be withheld for a period of 48 hours prior to elective pleural procedures

 

High thrombotic risk:

  • DOACs prescribed for high thrombotic risk indications should be withheld for a period of 48 hours prior to elective pleural procedures and a single bridging dose of enoxaparin 1mg/kg may be considered up to 24 hours prior to the pleural intervention

 

In all cases, assuming no bleeding complication, DOACs may be restarted 1824 hours post procedure i.e. the following morning

 

Some pleural procedures, particularly in the inpatient setting, may fall into a more urgent or ‘semi-urgent’ category due to the suspicion of pleural infection or a large pleural effusion causing significant resting dyspnoea. In these situations, the individual risks and benefits of a shorter period of DOAC cessation need to be considered and it may be appropriate to perform a procedure after stopping the medication for only 24 hours. 

 

  • Where renal function is abnormal (Creatinine clearance < 80 ml/min for dabigatran or < 30 ml/min for others), DOACs may need to be withheld for a longer period of time before pleural intervention. In this situation, haematology advice should be sought.

 

If an urgent procedure is required for a patient who has received a DOAC < 24 hours earlier, then haematology advice should be sought prior to intervention (with the obvious exception of a tension pneumothorax where immediate action is required). Specific reversal agents, prothrombin complex and/or tranexamic acid may be recommended either prophylactically or in response to a bleeding complication. In the rare instance of dabigatran use (less common in NHS GCC patients) then the specific antidote idarucizumab (Praxbind) can be found in the Pharmacy Emergency Fridge (dose 5g as two consecutive infusions of 2.5g/50mls over 5-10 minutes or as bolus injections).

5. Antiplatelet drugs

5.1    Aspirin

  • Aspirin cessation is not required prior to pleural procedures

5.2    Potent Antiplatelet Agents 

These drugs are typically prescribed for secondary prevention of ischaemic cerebrovascular disease (lifelong clopidogrel) or following acute coronary syndrome +/- percutaneous coronary intervention, typically dual antiplatelet therapy (DAPT) for 1-12 months depending on nature of intervention/stents used. 

 

  • Elective pleural procedures should not be performed in patients who have received potent antiplatelets (clopidogrel, ticagrelor, prasugrel) within the preceding 7 days

 

  • In patients taking potent antiplatelets who require an elective pleural procedure either:

 

  1. Defer procedure until potent antiplatelet no longer indicated if this is likely to occur within a clinically acceptable timescale

 

  1. Where longer term potent antiplatelet therapy is planned, pleural intervention should be deferred until at least 5 weeks following an acute ischaemic event (to allow at least 4 weeks of uninterrupted antiplatelet treatment)

 

  • Where DAPT is planned for greater than 4 weeks, discuss risk/benefit of stopping DAPT early with cardiologist

 

  • In patients taking long-term clopidogrel monotherapy consider substituting with aspirin for 7 days prior to planned pleural intervention

 

Where there has been a recent ischaemic event, the absolute need for a pleural intervention should be given particularly careful consideration. Assessment of effusion enlargement / regression on early follow-up imaging may in some cases remove the need for invasive testing.

Pleural interventions for urgent indications should not be delayed for cessation of potent antiplatelets. 5 Bleeding complications should be discussed urgently with a haematologist as treatment with tranexamic acid and platelet transfusion may be indicated.

6. References

  1. Psallidas, I. et al. Iatrogenic injury to the intercostal artery: aetiology, diagnosis and therapeutic intervention. Thorax 70, 802–804 (2015).
  2. Baldt, M. M. et al. Complications after emergency tube thoracostomy: assessment with CT. Radiology 195, 539–543 (1995).

  3. Havelock, T., Teoh, R., Laws, D., Gleeson, F.BTS Pleural Disease Guideline Group. Pleural procedures and thoracic ultrasound: British Thoracic Society Pleural Disease Guideline 2010. Thorax 65 Suppl 2, ii61–76 (2010).

  4. Ault, M. J., Rosen, B. T., Scher, J., Feinglass, J. & Barsuk, J. H. Thoracentesis outcomes: a 12-year experience. Thorax 70, 127–132 (2015).

  5. Keeling, D., Tait, R. C., Watson, H.British Committee of Standards for Haematology. Peri-operative management of anticoagulation and antiplatelet therapy. J. Haematol. 175, 602–613 (2016).

  6. Tait, R. C. Apixaban, Edoxaban & Rivaroxaban: Management of Haemorrhage, Surgery or other Invasive Procedures. NHS Greater Glasgow & Clyde Clinical Guideline. (2016).

  7. GGC Medicines Adult Therapeutics Handbook. NHS Greater Glasgow & Clyde.

  8. Kirchhof, P. et al. 2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 50, e1–e88 (2016).

7. Appendix 1: Flowchart for patients taking warfarin requiring elective pleural procedure

Last reviewed: 27 April 2018

Next review: 31 May 2022

Author(s): Dr Geoff Martin Senior Clinical Fellow in Pleural Disease, Queen Elizabeth University Hospital, Glasgow Dr Brian Choo-Kang Consultant Respiratory Physician, Glasgow Royal Infirmary, Glasgow

Approved By: NHSGGC Thrombosis Committee

Reviewer Name(s): NHS Greater Glasgow and Clyde Chest Drain Governance Group Dr Caroline O’Dowd Consultant Respiratory Physician, Queen Elizabeth University Hospital, Glasgow Dr Kevin Blyth Consultant Respiratory Physician, Queen Elizabeth University Hospital, Glasgow Dr Douglas Grieve Consultant Respiratory Physician, Royal Alexander Hospital, Paisley Dr Martin Johnson Consultant Respiratory Physician, Gartnavel General Hospital, Glasgow

Document Id: 637