Cardiac post-op patients: anti-coagulation therapy in PICU

What's New

28/03/19 Section on Warfarin Guidance updated

Objectives

  • To allow standardised anticoagulation practice in post-operative cardiac patients in PICU

  • Provide factual evidence base for staff administering or prescribing anticoagulation therapy.

Scope

This guideline applies to any post-operative cardiac patient being prescribed or administered anticoagulation therapy in PICU.

Audience

All healthcare professionals prescribing, supplying or administering anticoagulation therapy should be aware of this guideline.

Summary of anti-coagulation therapy for cardiac surgical procedures

Cardiac 
Operation

Immediate Post-operative 
Anticoagulation required?

Post‐op anticoagulation

Longer term  anticoagulation

BT Shunt /

Central Shunt*

Yes

Prophylactic heparin @ 20 units/kg/hr if no bleeding concern

  • Do not need to target specific aPTT range unless specific surgical concern / request
  • Check aPTT 4 hours after starting heparin and then once daily to ensure it is less than 80 (ie not over-anticoagulated)

 

Aspirin 3 ‐5mg/kg/day 

(max 75mg/day)

ASD/VSD

No

 

 

 

AVSD

No

 

 

 

Norwood Stage 1

Yes

Prophylactic heparin @ 20 units/kg/hr if no bleeding concern

  • Do not need to target specific aPTT range unless specific surgical concern / request
  • Check aPTT 4 hours after starting heparin and then once daily to ensure it is less than 80 (ie not over-anticoagulated)

Aspirin 3‐5mg/kg/day

(max 75mg/day)

 

Glenn / BCPC

 Yes

Prophylactic heparin @ 20 units/kg/hr if no bleeding concern

  • Do not need to target specific aPTT range unless specific surgical concern / request
  • Check aPTT 4 hours after starting heparin and then once daily to ensure it is less than 80 (ie not over-anticoagulated)

 Aspirin 3‐5mg/kg/day

(max 75mg/day)

Start day 2 if meet criteria below.

Fontan / TCPC

Yes

Therapeutic heparin regime if no bleeding concern

  • Target aPTT 60‐90 using dose adjustment suggestions in "Therapeutic heparin regime" noted below
  • Continue heparin until INR above 2.0

Warfarin for 6 months post-op

Target INR 2.5 

(Range 2‐3)

If intolerance or contraindication to warfarin or it is against family wishes consider aspirin

TGA

No

 

 

 

Tetralogy of Fallot

No

 

 

 

TAPVD

No

 

 

Hybrid Procedure

(stented PDA)

 

Yes

Prophylactic heparin @ 20 units/kg/hr if no bleeding concern

  • Do not need to target specific aPTT range unless specific surgical concern / request
  • Check aPTT 4 hours after starting heparin and then once daily to ensure it is less than 80 (ie not over-anticoagulated)

Aspirin 3 ‐5mg/kg/day 

(max 75mg/day)

* In shunts anticoagulation therapy should be instituted as soon as safely possible. Start heparin infusion providing bleeding is not an issue (chest drain loss is less than 3ml/kg/hr) and post-op aPTT is less than 60.

Anticoagulation for Valve Surgery

Cardiac Operation

Post-operative 
Anticoagulation required?

Immediate Post-op  anticoagulation

Longer term anticoagulation

Homograft Valves

(aortic/pulm)

Ross Procedure

Yes

Not required

Aspirin 3-5mg/kg/day

(max 75mg/day) until at least 3 months post-op

Prosthetic valve

(Contegra, Mosaic,

Freestyle, Hancock)

 

Yes

 

Not required

Aspirin 3-5mg/kg/day

(max 75mg/day) until at least 3 months post-op

(Consider warfarin for 3 months if significant thrombogenic risk: INR Target 2.5 with range 2-3)

Valve repairs

Yes

Not required

Aspirin 3-5mg/kg/day

(max 75mg/day) until at least 3-6 months post-op when pericardial patch or annuloplasty ring used

Mechanical Valves

(St Judes, Medtronic)

Yes

Prophylactic heparin @ 20 units/kg/hr if no bleeding concern

  • Do not need to target specific aPTT range unless specific surgical concern / request
  • Check aPTT 4 hours after starting heparin and then once daily to ensure it is less than 80 (ie not over-anticoagulated)
  • Continue heparin until INR above 2.0

Warfarin

Aortic valve: INR 2.5 (Range 2-3)

Mitral valve: INR 3 (Range 2.5-3.5)

 Generally heparin is not titrated to APTT unless there is a specific surgical request.  Routine coagulation measures should be assessed as noted below.

Standard prophylactic Heparin regime

For most operations where heparin is used we will run heparin at 20iu/kg/hr if long term warfarinisation is not required. The situations where this is required are noted above. Loading dose is not required.

Preparation:

  • Prepare infusion using 1000units/kg of heparin sodium, diluted to 50ml with 0.9% sodium chloride.
    • Infusion rate of 1.0 ml/hr = 20 units/kg/hr 

Monitoring:

  • Clotting profile (APTT, PT and fibrinogen) should be checked as follows:
    • On arrival back from theatre
    • 4 hours after INITIAL commencement of heparin infusion
    • One hour after a syringe is changed (request aPTT only - upper limit of 80 is acceptable)
    • Once daily whilst on heparin infusion

  • Platelets
    • Check platelets daily
    • If platelets drop by >50% from baseline consider Heparin Induced Thrombocytopenia (HIT), this is more likely after 5-10 days of treatment. However there are many other reasons for thrombocytopenia (NEC /infection etc) Notify consultant. Consider sending HIT antibody screen.
Therapeutic Heparin regime

"Chasing the aPTT":

For most operations it is not routine to chase aPTT - see table above or specific surgical guidance

Loading dose is not required if recently returned from cardiac theatre

Heparin management:

  • Prepare infusion using 1000units/kg of heparin sodium, diluted to 50ml with 0.9% sodium chloride:
    • ONLY IF APTT <50s: give initial loading dose of 50 units/kg (2.5ml) over ten minutes and run at 20units/kg/hr (do not load if just returned from theatre)
    • IF APTT 60-90s: Run infusion at 20units/kg/hr (1ml/hr) and check APTT in 4 hours.
    • Manage heparin titration as follows aiming for an APTT of 60‐90 unless specific instructions 

  • Monitoring:
    • Clotting profile (APTT, PT and fibrinogen) should be checked as follows: 
      • On arrival back from theatre
      • 4 hours after INITIAL commencement of heparin infusion
      • One hour after a syringe is changed (request APTT only)
      • Once daily whilst on heparin infusion
         
    • Platelets
      • Check once a day whilst on heparin
      • If platelets drop by >50% from baseline consider Heparin Induced Thrombocytopenia (HIT), this is more likely with 5- 10 days of treatment. However there are many other reasons for thrombocytopenia (NEC /infection etc) Notify consultant.
APTT (s) Bolus
(units/kg)
Stop infusion Rate
Change
Recheck
APTT (hr)
<50 50 units/kg



+10%
+10%
4 hours time
50-59




4 hours time
60-90   Next day
90-99 -10%
-10%
4 hours time
100-120 For 30 min 4 hours time
>120 For 60 min -15% 4 hours time


The need for more than 40 units/kg/hr of heparin to achieve APTT should be made known to the consultant. In this situation consider measuring anti‐Xa level or anti‐thrombin level (This will be age dependent). It is not unusual for a child <1yo to require up to 40units/kg/hr to achieve therapeutic APTT levels. 

Once the APTT is achieved and the heparin infusion is stable – once daily clotting profile is acceptable. 

Procedures whilst on Heparin or Warfarin

Heparin:

  • If patients are prophylactically heparinised and/or aPTT is <60  
    • Chest drain removal or insertion -no need to stop heparin prior to procedure
    • Intra-cardiac line & pacing wire removal – stop heparin for 2 hours prior to procedure and check aPTT is <60 and platelet count is >100 within 6 hours period prior to removal of lines or wires.
  • If patients are therapeutically heparinised and/or aPTT >60 heparin should be stopped for 2 hours prior to procedures including insertion/removal chest drains (unless clinical emergency), removal of intra-cardiac lines or removal of pacing wires. Send a standard coagulation profile and Full blood count 2 hours after stopping heparin and check aPTT is <60 and Platelet count is >100 prior to any procedure. If any doubt repeat & discuss with Duty Intensivist. 

 Warfarin:

  • Chest drains & pacing wires can be removed if INR <3.0
    • If INR>3.0 discuss with Duty Cardiac Surgeon & Haematologist
  • Intra-cardiac lines should be removed prior to initiation of warfarin
Reversal of Unfractionated Heparin Therapy

If anticoagulation with heparin needs to be discontinued for clinical reasons, termination of the heparin infusion will usually suffice due to the rapid clearance of heparin.

If an immediate effect is required IV protamine sulphate will reverse heparin therapy.

The dose of protamine required is based on the amount of heparin received in the preceding 2 hours (see below & also BNF). Maximum Protamine dose is 50 mg.

Time since last heparin dose Protamine dose
<30 mins 1mg / 100 units heparin received
30-60 mins 0.5mg-0.75mg/100 units heparin received
60-120 mins 0.375mg-0.5mg/100 units heparin received
>120 mins 0.25mg-0.375mg/100 units heparin received

Protamine infusion is usually given undiluted (10 mg/ml) at a rate not exceeding 5 mg/min. May be diluted in sodium chloride 0.9% if required.

Hypersensitivity reactions to protamine sulphate may occur in patients with known hypersensitivity reactions to fish or those previously exposed to protamine therapy or protamine-containing insulin. Significant hypotension may occur in these cases.

Aspirin guidance

Must fulfil the following criteria to start aspirin:

  • Chest closed
  • Major intracardiac lines removed (pulmonary arterial/ left atrial lines)
  • Absorbing feed

Aspirin is commenced at 3-5mg/kg (max 75mg) once daily.

Stop heparin after 2nd dose of aspirin.

Warfarin guidance

It is unusual to start warfarin whilst the patient is in the ICU – always check with Duty Intensivist. If the patient is already on an intravenous heparin infusion then the heparin must be continued until the INR is >2.0.

In the Fontan patient warfarin is usually commenced when the patient meets the following criteria:

  • Intracardiac lines (LA/PA) removed
  • Absorbing feeds

Patients with mechanical valves should be considered for warfarin if still in PICU after 48 hours. 
Again, any heparin infusion should continue until the INR is >2.0.
Special consideration needs to be taken with regards to timing of drain and line removal. Seek consultant advice.

Intra-cardiac lines should ideally be removed prior to the initiation of Warfarin.
Chest drains or pacing wires should NOT be removed if an INR is greater than 3.0

Target INR as follows:

 

  • Fontan                                   

2.0 – 3.0 

  • Aortic valve replacement 

2.0 – 3.0 

  • Mitral valve replacement 

2.5 – 3.5 

 

To achieve an INR of 2-3 follow the instructions below:

  • Check daily INR. Usually takes 3-5 days to load and then maintenance therapy commences.
  • Loading dose: Check INR. If INR 1.0-1.3 (if high liase with haematology)
    • Day 1 Dose = 0.2 mg/kg orally once daily
    • Loading days 2-4: Depends on INR as below:
INR Warfarin dose (once daily)
1.1-1.3 Repeat loading dose
1.4-1.9 Give 50% of loading dose
2.0-3.0 Give 50% of loading dose
3.1-3.5 Give 25% of loading dose
>3.5 Hold until INR <3.5. Restart at 50% previous dose
  • Maintenance dose (D5 onwards):
INR Warfarin dose
1.1-1.4 Increase dose by 20%
1.5-1.9 Increase dose by 10%
2.0-3.0 No change in dose
3.1-3.5 Decrease dose by 10%
>3.5 Hold until INR < 3.5 then restart at 20% less than previous dose

For reversal of warfarin consult BNF and the Royal Hospital for Children anti‐thrombotic protocol 

Low Molecular Weight Heparin (LMWH) or Enoxaparin therapy

Therapeutic Enoxaparin dose regime

Enoxaparin comes in vials of 20mg (0.2ml) and 40mg (0.4ml)

Enoxaparin should be continued for between 6 weeks and 3 months post‐diagnosis of a venous thrombo-embolism (VTE). Ensure referral to Drs Chalmers or Pinto (Consultant Haematologists RHC). Remove CVL associated with VTE as soon as possible. Ensure follow‐up ultrasound to screen for extension of VTE. 

  • < 2 months or <5kg
    • 1.5mg/kg twice daily subcutaneously
    • Ideally prescribe for 0600Hrs & 1800Hrs (but do not delay commencing treatment unless converting from UFH)
    • Administer dose via SC injection (insuflon should not be used)
  • >2 months or > 5kg
    • 1mg/kg twice daily subcutaneously
    • Ideally prescribe for 0600Hrs & 1800Hrs 
    • Administer dose via SC injection (insuflon should not be used)

Therapeutic Enoxaparin monitoring regime

  • Check anti‐Xa assay 4 hours after 1st dose
    • Order anti‐Xa assay on Trakcare under “anti Xa activity – child”, stating Enoxaparin therapy and dose regime and time of last dose.
  • Target anti‐Xa assay 0.5 – 1.0 U/ml
  • Dose adjust as per chart below
  • Repeat anti‐Xa assay 4 hrs after 3rd dose and dose adjust as per chart
  • Once target anti‐Xa levels are achieved, re‐ check every Monday & Thursday
  • Remember anti‐Xa results will be affected by:
    • Use of Unfractionated Heparin
    • Delayed excretion of LMWH e.g. in renal failure
    • Hepatic failure
    • Coexisting coagulopathy e.g. in sepsis
    • Increase frequency of anti‐Xa assay if:
      • Bleeding concern
      • Planned surgery 

Anti‐Xa level

Dose adjustment

Next anti‐Xa level

<0.35

Increase dose by 25%

4 hrs post dose

0.35 – 0.49

Increase dose by 10%

Next day

0.5 – 1.0

Next Monday or Thursday

1.01 – 1.5

Decrease dose by 10%

Next day

1.51 ‐ 2.0 

Delay dose by 12hrs & decrease by 25%

 

>2

Delay dose till Anti‐Xa is <1.0
Decrease dose by 40%

Check anti‐Xa every 12 hrs till <1.0
Check anti‐Xa 4 hrs after dose


Prophylactic Enoxaparin therapy

Enoxaparin comes in vials of 20mg (0.2ml) and 40mg (0.4ml). 

Venous thromboprophylaxis (VTE) with Enoxaparin should be used in combination with measures including early mobilisation, removal of CVL’s and TED stockings (see appendix VTE Risk assessment). 

  • < 2 months or <5kg
    • 0.75mg/kg twice daily subcutaneously
    • Prescribe for 0600Hrs & 1800Hrs 
    • Administer dose via SC injection (insuflon should not be used)
  • >2 months or > 5kg
    • 0.5mg/kg twice daily subcutaneously
    • Prescribe for 0600Hrs & 1800Hrs 
    • Administer dose via SC injection (insuflon should not be used)

Prophylactic Enoxaparin monitoring regime

  • Check anti‐Xa assay 4 hrs after 3rd dose
    • Order anti‐Xa assay on Trakcare under “anti Xa activity – child”, stating Enoxaparin therapy and dose regime and time of last dose.
  • Target anti‐Xa assay 0.3 – 0.5 U/ml
  • Dose adjust as per chart below
  • Once target anti‐Xa lavels are achieved, re‐check every Monday 
  • Remember anti‐Xa results will be affected by:
    • Use of Unfractionated Heparin
    • Delayed excretion of LMWH e.g. in renal failure
    • Hepatic failure
    • Coexisting coagulopathy e.g. in sepsis
  • Increase frequency of anti‐Xa assay if:
    • Bleeding concern
    • Planned surgery 

Anti‐Xa level

Dose adjustment

Next anti‐Xa level

<0.3

Increase dose by 25%

4 hrs post dose

0.3 – 0.5

4 hrs post dose on next Monday

0.5 – 1.0

Decrease dose by 25%

Next day

>1.0

Delay dose till Anti‐Xa is <0.5
Decrease dose by 40%

Check anti‐Xa every 12 hrs till <1.0
Check anti‐Xa 4 hrs after dose

Central Venous Line (CVL) thrombosis guidance

Venous thrombosis is not uncommonly found in post-operative cardiac patients. There is no evidence that prophylactic heparin prevents clot formation. [1] [8]

Unless there are other bleeding concerns the following steps should be taken:

  1. If possible the CVL associated with the clot should be removed as soon as possible
  2. Therapeutic anticoagulation with heparin should be commenced (See therapeutic heparin section).
  3. Review evidence of the clot radiologically (ultrasounds is ideal) between day 3-5
    1. If there is no clot evident or only a small clot visible with good blood flow then heparin can be stopped & no other investigations are required
    2. If the clot extends or remains present on radiological review then therapeutic anticoagulation with heparin should be continued. (See therapeutic heparin section). Heparin can be converted to therapeutic LMWH (Enoxaparin). Length of treatment will be determined by radiological and clinical review with the haematology teams.  

Following resolution of clot, if the CVL remains in-situ prophylactic LMWH should continue until the CVL can be removed. [1]

Guidance and advice should be sought from Duty Haematology Consultant. 

Appendix: Adolescent risk assessment for venous thromboembolism (VTE)
References
  1. Monangle,P. et al. Antithrombotic therapy in neonates and children: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 133, 887S-968S (2008).
  2. Lok,J.M., Spevak,P.J. & Nichols,D.G. Critical heart disease in infants and children. Philadelphia, PA: Mosby. (2010).
  3. Motz,R., Wessel,A., Ruschewski,W. & Bursch,J. Reduced frequency of occlusion of aorto-pulmonary shunts in infants receiving aspirin. Cardiol. Young. 9, 474-477 (1999).
  4. Tweddell,J.S. Aspirin: a treatment for the headache of shunt dependent pulmonary blood flow and parallel circulation? Circulation 116, 236-237 (2007).
  5. Mullen,J.C., Lemermeyer,G. & Bentley,M.J. Modified Blalock-Taussig shunts: to heparinize or not to heparinize? Can. J. Cardiol.12, 645-647 (1996).
  6. Andrew,M. Anticoagulation and thrombolysis in children. Tex. Heart Inst. J. 19, 168-177 (1992).
  7. BNF-C
  8. Schroeder A, Axelrol D, Silverman N et al. A continous heparin infusion does not prevent catheter-related thrombosis in infants after cardiac surgery. Pediatric Crit Care Med 11,489-495 (2010).
  9. McCrindle BW et al. Factors associated with thrombotic complications after the Fontan procedure: a secondary analysis of a multicenter, randomized trial of primary thromboprophylaxis for 2 years after the Fontan procedure.J Am Coll Cardiol. 22 61, 346‐53 (2013)
  10. Potter BJ et al. Effect of aspirin and warfarin therapy on thromboembolic events in patients with univentricular hearts and Fontan palliation. Int J Cardiol. 168,3940‐3 (2013) 
  11. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, Iung B, Lancellotti P, Lansac E, Muñoz DR, Rosenhek R, Sjögren J, Tornos Mas P, Vahanian A, Walther T, Wendler O, Windecker S, Zamorano JL; 2017 ESC/EACTS Guidelines for the management of valvular heart disease. ESC Scientific Document Group. Eur Heart 2017 Sep 21;38(36):2739-2791.
Editorial Information

Last reviewed: 27 May 2019

Next review: 20 January 2020

Author(s): Mark Davidson

Version: 3.0

Co-Author(s): P Noonan, B Knight, A McLean, E Peng, K McArthur, E Chalmers

Approved By: Paediatric & Neonatal Clinical Effectiveness & Risk Committee