Anticoagulation Therapy for Post-op Cardiac Patients in PICU

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.

"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.

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. 

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

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.

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.

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.

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

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:

• Maintenance dose (D5 onwards):

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

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 1^st 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 3^rd 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 

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 3^rd 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 

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. 

Adolescent risk assessment for venous thromboembolism (VTE)