Venous Thromboembolism, Catheter-Related, CICU/CCU — Enoxaparin Dosing - Initiation of Therapy — Clinical Pathway: ICU and Inpatient

Venous Thromboembolism (VTE) Catheter-Related, Clinical Pathway — CICU and CCU

Enoxaparin Dosing, Administration, Special Considerations
and Monitoring

Initiation of Therapy

Enoxaparin, a low molecular weight heparin (LMWH), is the anticoagulant of choice for primary prophylaxis and treatment of thromboembolism on formulary at CHOP.

Potential Advantages of LMWH

  • Need for minimal monitoring
  • Lack of interference by other drugs or diet, unlike warfarin
  • Reduced risk of heparin-induced thrombocytopenia (HIT)
  • Reduced risk of osteoporosis with long-term use compared to that of heparin

Drug Characteristics

Half-life 4 hrs
Peak Levels 3-5 hrs after subcutaneous injection
Clearance
  • Renal
  • If CrCl is < 30 mL/min
    • Consult Hematology or Pharmacy for dose adjustment or alternative therapy
Special Considerations for Infants < 3 mos
or < 5 kgs
  • Increased dose requirements due to large volume of distribution and low antithrombin levels
  • Prior published dose recommendations are often inadequate
  • Doses here are updated to reflect current practice and are more likely to achieve a therapeutic range

Recommended Dose

Age Dose
< 3 mos or < 5 kg 1.7 mg/kg subcutaneous q12hr
3 mos to 2 yrs 1.2 mg/kg subcutaneous q12hr
> 2 yrs 1 mg/kg subcutaneous q12hr
BMI > 30-50
BMI > 50 consult pharmacy		 0.8 subcutaneous q12hr
Max 170 mg

Enoxaparin Administration

Special Considerations for Enoxaparin Use

See Clinical Practice Guidelines

Minor Procedures That Result in Bleeding
  • IM Injections/Arterial Punctures
    • Avoid if at all possible
    • Apply adequate pressure applied post-procedure if required
  • Invasive Procedures
    • NG tube insertion, intubation, rectal temperature, biopsy
Elective Invasive Procedures Discontinue enoxaparin at least 24 hrs before an elective invasive procedure
Medication Interaction
  • Medications that affect platelet function may potentiate risk of hemorrhage:
    • Aspirin
    • NSAID
    • Dipyridamole
    • Clopidogrel
    • Cangrelor
Complications
Stop enoxaparin and consult Hematology/Cardiac Thrombosis Team urgently
  • Bleeding requiring transfusion
    • Intracranial hemorrhage
  • Overanticoagulation requiring reversal with protamine
  • Heparin Induced Thrombocytopenia
    • Suspect if on uFH or LMWH and unexplained drop in platelet count > 50% from baseline
    • Rare, typically occurs 5-10 days post any heparin exposure

Enoxaparin Monitoring

Heparin anti-Xa level using assay for LMWH.
Refer to Initiation and Maintenance of Enoxaparin (Lovenox).

Goal anti-Xa Level 0.5-1.0 IU/mL
Timing of Lab Draw
  • 4 hrs (range 3-5 hrs) after 2nd dose upon initiation
  • After dose changes
  • When concerned for bleeding
Ideal Sample
Neonates
  • Weekly while inpatient
  • 2 anti-Xa levels are within therapeutic range, space to every other week
1-18 yrs Every other week while inpatient or more frequently if concern for deteriorating
renal function
≥ 18 yrs
  • Not required if:
    • Normal renal function
    • and
    • Non-obese (≤ 100 kg or ≤ BMI 30 kg/m2) or non-malnourished (weight ≥ 45 kg)

Nomogram for Adjusting Enoxaparin Dose

Anti-Xa Level
(units/mL)		 Dose Change Repeat Anti-Xa Level
< 0.35 Increase 25% 4 hrs after 2 doses
0.35-0.49 Increase 10%
0.5-1.0 None See Table Above
1.1-1.5 Decrease by 20% 4 hrs after 2 doses
1.6-2.0 Decrease by 30%
> 2.0
  • Hold all subsequent doses
  • Measure anti-factor Xa level q12h until < 0.5 units/mL
  • Check for rising creatinine
  • Restart at 40% less than original dose

Enoxaparin Reversal

  • Requires a high level of caution when prescribing and administering.
  • Protamine sulfate reverses LMWH approximately 70%.
  • Rate not to exceed 5mg/min. If administered too rapidly may cause cardiovascular collapse.
  • Children with known allergy to fish, and those who have received protamine-containing insulin or previous protamine therapy may be at risk of hypersensitivity reactions to protamine sulfate.
  • Refer to Protamine Monograph

Nomogram, Dosing for Enoxaparin Reversal

Protamine dose based on amount of enoxaparin and the time since the last dose.

Time Since Last Enoxaparin Dose Protamine Dose per 1 mg Enoxaparin Received
Max 50 mg
< 4 hrs 1 mg per 1 mg enoxaparin received
4-8 hrs 0.5-0.75 mg per 1 mg enoxaparin received
8-12 hrs 0.25-0.5 mg per 1 mg enoxaparin received
> 12 hrs Do not give protamine

Converting from LMWH to uFH

  • Begin unfractionated heparin (uFH) no earlier than 8 hrs after the last dose of LMWH
  • If starting within 8-12 hrs, do not use bolus of uFH

Guidance for Holding Prior to Elective Procedures

  • Hold 2 enoxaparin doses prior to surgical procedure or lumbar puncture; there may be exceptions for very high-risk children
  • Minimum of 24 hrs between last dose and procedure
  • Restart enoxaparin when clinician responsible for the invasive procedure deems it safe from a bleeding perspective to restart anticoagulation with agreement from the Cardiac Thrombosis Team