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

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

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]
• 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

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