Indications
Cardiac
- Acute Coronary Syndrome (see Coronary Artery Disease)
- Atrial Fibrillation (see Atrial Fibrillation)
Pulmonary
Prophylaxis Against Venous Thromboembolism
- xxx
Treatment of Venous Thromboembolism
- Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)
- Deep Venous Thrombosis (DVT) Prophylaxis (see Deep Venous Thrombosis)
Other Indications for Anticoagulation
- xxxx
Pharmacology
Enoxaparin is a Low Molecular Weight Heparin
- Commercially Available Low Molecular Weight Heparins are Derived from Unfractionated Heparin by Chemical or Enzymatic Depolymerization
- Low Molecular Weight Heparins are Chemically and Pharmacokinetically Distinct from Each Other
- Advantages of Low Molecular Weight Heparins Over Unfractionated Heparin
- Low Molecular Weight Heparins Have Greater Bioavailability than Unfractionated Heparin
- Low Molecular Weight Heparins Have Been Extensively Used Via the Subcutaneous Route: allows for outpatient administration
- Low Molecular Weight Heparins Have a Greater Duration of Action than Unfractionated Heparin: allows for once-twice daily dosing
- Low Molecular Weight Heparins Have a Better Correlation Between Dose and Anticoagulant Response: allows for fixed dosing without monitoring
- Low Molecular Weight Heparins Have a Generally Lower Risk of Heparin-Induced Thrombocytopenia than Unfractionated Heparin (see Heparin-Induced Thrombocytopenia)
- Low Molecular Weight Heparins Have a Lower Incidence of Osteoporosis (see Osteoporosis)
- Disadvantages of Low Molecular Weight Heparins, as Compared to Unfractionated Heparin
- Low Molecular Weight Heparins Have a Slightly Delayed Onset of Action (20-30 min), as Compared to the Instantaneous Onset of Action of Unfractionated Heparin
- Low Molecular Weight Heparins Have a Longer Duration of Action, Making Discontinuation of Therapy More Difficult
- Low Molecular Weight Heparins are Less Easily Activated with Protamine Sulfate (see Protamine)
- Low Molecular Weight Heparins Have a Prolonged Half-Life in Patients with Renal Failure (Especially with Enoxaparin)
- If Monitoring is Required for Low Molecular Weight Heparin Use, Anti-Factor Xa Activity Testing with a Rapid Turnaround Time May Not Be Available at All Institutions
- Enoxaparin (and All Heparins) Act by Binding to Antithrombin (Previously Called Antithrombin III, Also Known as Heparin Cofactor I)
- Binding to Antithrombin is Mediated by a Pentasaccharide Sequence Which is Randomly Distributed Along the Heparin Chains
- Binding of Heparins to Antithrombin Induces a Conformational Change in Antithrombin, Resulting in Conversion to a More Rapid Inactivator of Coagulation Factors (Thrombin/Factor IIa and Factor Xa): the enhancement of antithrombin activity is approximately 1000-4000 fold
- While Both Unfractionated Heparin and Low Molecular Weight Heparins Efficiently Inactivate Factor Xa, Unfractionated Heparin is a More Efficient Inactivator of Thrombin/Factor IIa
- Fondaparinux is a Pure Anti-Factor Xa Inhibitor
Metabolism
- Hepatic: low molecular weight heparins are metabolized in the liver and excreted by the kidneys
- CrCl <30 mL/min: may lead to significantly increased plasma levels of low molecular weight heparins
Administration
Venous Thromboembolism Prophylaxis
- SQ: 40 mg qday or xxx
- Dose Adjustment for Organ Dysfunction
- Hepatic: xxx
- Renal: xxx
- Use in Pregnancy (see Pregnancy)
- Enoxaparin does not cross the placenta, making it the anticoagulant of choice in pregnancy
- Use in Breastfeeding
- Low molecular weight heparins do not accumulate in breast milk
Therapeutic/Full-Dose Anticoagulation
- SQ: 1 mg/kg q12hrs
- Dose Adjustment for Organ Dysfunction
- Hepatic: xxx
- Renal: xxx
Enoxaparin Dosing in the Setting of Obesity (see Obesity)
- Proposed Enoxaparin Dosing Regimen in Morbid Obesity (NEJM, 2014) [MEDLINE]
- Dose for Body Mass Index (BMI) >40 or Weight >200 kg (441 lbs) = 0.75 mg/kg (Actual Body Weight)
- Monitoring with Anti-Factor Xa Activity Levels is Recommended Due to Variable Absorption in the Setting of Morbid Obesity (see Anti-Factor Xa Activity): should be considered in this population
- Measure Anti-Factor Xa Activity Level 4 hrs After the Enoxaparin Dose
- Factor Xa Activity Level is Inversely Proportional to the Amount of Heparin or Other Factor Xa Inhibitor Present in the Plasma
- Therapeutic Range (When Measured 4-6 hrs After Injection): 0.5-1.0 anti-Xa units/mL
- Literature Review of Enoxaparin Dosing for Patients at Extremes of Weight (Ann Pharmacother, 2018) [MEDLINE]
- Measure Anti-Factor Xa Activity Level 4 hrs After the Enoxaparin Dose
- Low Body Weight Patients May Benefit from Enoxaparin 30 mg SQ qday for Venous Thromboembolism Prophylaxis, and Standard Weight-Based Dosing for Venous Thromboembolism Treatment
- In Patients with BMI ≥40 kg/m2, Enoxaparin 40 mg SQ BID is Recommended for Venous Thromboembolism Prophylaxis
- In Patients with BMI ≥50 kg/m2, Consideration Should Be Given for Higher Doses for Venous Thromboembolism Prophylaxis
Enoxaparin Use in Pregnancy (see Pregnancy)
- Enoxaparin does not cross the placenta, making it the anticoagulant of choice in pregnancy
Enoxaparin Use During Breast Feeding
- Low Molecular Weight Heparins Do Not Accumulate in Breast Milk
Effect of Enoxaparin on Anticoagulation Tests
- Prothrombin Time (PT)/International Normalized Ratio (INR) (see Prothrombin Time): no effect
- Enoxaparin is an indirect thrombin inhibitor and should theoretically prolong the INR: however, most INR assay reagents contain heparin-binders which block the effect of heparin (or similar agents) at concentrations <1 unit/mL -> therefore, at heparin concentration of >1 unit/mL, the INR may be prolonged
- Partial Thromboplastin Time (PTT) (see Partial Thromboplastin Time): no effect-prolonged
- Anti-Factor Xa Activity (see Anti-Factor Xa Activity): prolonged
Periprocedural/Perioperative Management of Enoxaparin Anticoagulation

Recommendations for Periprocedural/Perioperative Management of Coumadin (American College of Chest Physicians Clinical Practice Guideline for the Perioperative Management of Antithrombotic Therapy) (Chest, 2022) [MEDLINE]
- In Patients Receiving Low Molecular Weight Heparin (as Part of Bridging Regimen or Not) for an Elective Procedure/Surgery, Administer the Last Preprocedure/Preoperative Low Molecular Weight Heparin Dose Approximately 24 hrs Before the Elective Procedure/Surgery (as Opposed to Administering the Last Dose 10-12 hrs Before the Elective Procedure/Surgery (Conditional Recommendation, Very Low Certainty of Evidence)
- In Patients Receiving Low Molecular Weight Heparin (as Part of Bridging Regimen or Not) for an Elective Procedure/Surgery, Administer the First Postprocedure/Postoperative Low Molecular Weight Heparin Dose at Least 24 hrs After the Procedure/Surgery (as Opposed to Administering it <24 hrs After the Procedure/Surgery (Conditional Recommendation, Very Low Certainty of Evidence)
- Low-Moderate Bleeding Risk Procedure/Surgery
- Wait at Least 24 hrs Before Resuming Low Molecular Weight Heparin
- High Bleeding Risk Procedure/Surgery
- Wait at least 48-72 hrs Before Resuming Low Molecular Weight Heparin
- For Patients in Whom the Management Plan is to Delay Resumption of Low Molecular Weight Heparin for 48-72 hrs and Who are at High Risk for Postprocedural/Postoperative Venous Thromboembolism, Low-Dose Low Molecular Weight Heparin Can Be Administered for the Initial 2-3 Days Before the Transition to Full-Dose Low Molecular Weight Heparin Anticoagulation
- Low-Moderate Bleeding Risk Procedure/Surgery
- In Patients Receiving Low Molecular Weight Heparin (as Part of Bridging Regimen or Not) for an Elective Procedure/Surgery, Administer Half the Total Daily Dose of Low Molecular Weight Heparin the Day Prior to the Elective Procedure/Surgery (as Opposed to Administering the Full Dose of Low Molecular Weight Heparin the Day Prior (Conditional Recommendation, Very Low Certainty of Evidence)
- This Guidance May Apply More to Patients having a High Bleeding Risk Procedure/Surgery (Including Patients Having Neuraxial, Spinal or Epidural, Anesthesia, Rather than in Patients Having a Low-Moderate Bleeding Risk Procedure/Surgery
- Administering Half the Total Daily Dose of Low Molecular Weight Heparin Can Be Done by Giving, on the Morning of the Day Before the Procedure/Surgery, Only the Morning Dose of a BID Low Molecular Weight Heparin Regimen or Approximately 50% of the Dose of a Once Daily Low Molecular Weight Heparin Regimen
- In Patients Receiving Low Molecular Weight Heparin (as Part of Bridging Regimen or Not) for an Elective Procedure/Surgery, Measurement of Anti-Factor Xa Levels is Not Routinely Recommended to Guide Perioperative Low Molecular Weight Heparin Management (Conditional Recommendation, Very Low Certainty of Evidence)
- There May Be Select Patients Undergoing High Bleeding Risk Procedures/Surgeries (Intracranial, Spinal, etc) or Patients Who Require an Urgent (Non-Elective) Procedure/Surgery Where Anti-Factor Xa Measurement May Be Considered
Reversal of Enoxaparin Anticoagulation
XXXX
- xxxxx
Adverse Effects
Hematologic Adverse Effects
Heparin-Induced Thrombocytopenia (HIT) (see Heparin-Induced Thrombocytopenia)
- Epidemiology
- XXXX
- Clinical
- XXXXX
Hemorrhagic Adverse Effects
- Adrenal Hemorrhage (see Adrenal Insufficiency)
- Diffuse Alveolar Hemorrhage (DAH) (see Diffuse Alveolar Hemorrhage)
- Epistaxis (see Epistaxis)
- Gastrointestinal Hemorrhage (see Gastrointestinal Hemorrhage)
- Hematuria (see Hematuria)
- Intracerebral Hemorrhage (Hemorrhagic Cerebrovascular Accident) (see Intracerebral Hemorrhage)
- Intracranial Epidural Hematoma (see Intracranial Epidural Hematoma)
- Retroperitoneal Hemorrhage (see Retroperitoneal Hemorrhage)
- Spinal Epidural Hematoma (see Spinal Epidural Hematoma)
- Subarachnoid Hemorrhage (SAH) (see Subarachnoid Hemorrhage)
- Subdural Hematoma (SDH) (see Subdural Hematoma)
Other Adverse Effects
- xxx
References
General
- Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 Suppl):141S [MEDLINE]
- Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3 [MEDLINE]
- Perioperative Management of Antithrombotic Therapy: An American College of Chest Physicians Clinical Practice Guideline. Chest. 2022 Aug 11;S0012-3692(22)01359-9. doi: 10.1016/j.chest.2022.07.025 [MEDLINE]
Indications
- Fibrinolysis for patients with intermediate risk pulmonary embolism. N Engl J Med 2014;370:1402–1411 [MEDLINE]
Administration
- Dosing in heavy-weight/obese patients with the LMWH, tinzaparin: a pharmacodynamic study. Thromb Haemost. 2002;87(5):817 [MEDLINE]
- The safety of dosing dalteparin based on actual body weight for the treatment of acute venous thromboembolism in obese patients. J Thromb Haemost. 2005;3(1):100 [MEDLINE]
- Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother. 2009;43(6):1064 [MEDLINE]
- Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations. Ann Pharmacother. 2018 Sep;52(9):898-909. doi: 10.1177/1060028018768449 [MEDLINE]
Adverse Effects
- XXXX