Low Molecular Weight Heparin

Aka: Low Molecular Weight Heparin, Low-Molecular Weight Heparin, LMW Heparin, LMWH, Ardeparin, Normiflo, Danaparoid, Orgaran, Tinzaparin, Innohep

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II. Indications

  1. Venous Thromboembolism Treatment
    1. See Anticoagulation in Thromboembolism
    2. Deep Vein Thrombosis
    3. Pulmonary Embolism
  2. Deep Vein Thrombosis Prophylaxis
    1. General Surgery
    2. Orthopedic Surgery (Hip, Knee)

III. Contraindications (Indications for standard Heparin)

  1. Previous Deep Vein Thrombosis history
    1. Ipsilateral DVT
    2. Two or more DVTs
    3. Any Venous Thromboembolism
  2. High risk lesion (e.g. Iliofemoral DVT)
  3. Pregnancy
  4. Renal Insufficiency (Creatinine Clearance <30 due to risk of dose stacking and bleeding risk)
  5. Morbidly obese patients (consider Unfractionated Heparin where BMI>40-45 kg/m2)
  6. Hepatic Insufficiency
  7. Active bleeding
  8. Surgery in prior 5-7 days (However see below)
  9. Hypercoagulable state
    1. Protein C Deficiency
    2. Protein S Deficiency
    3. Antithrombin III Deficiency
  10. Inability to undergo outpatient treatment
  11. Noncompliance
  12. Thrombocytopenia
  13. Coagulopathy
  14. Active Peptic Ulcer Disease

IV. Mechanism

  1. See Intrinsic Clotting Pathway
  2. LMWH, like Heparin, binds to, and potentiates Antithrombin III (AT III)
    1. Antithrombin III binds to an inhibits Factor Xa
    2. Results in decreased Thrombin (and ultimately Fibrin) formation
  3. In contrast to Heparin
    1. LMHW is a small fragment of the larger Heparin molecule (mucopolysaccharide)
    2. Heparin also binds Thrombin (LMWH only acts at AT III

V. Efficacy: Unstable Angina and Myocardial Infarction

  1. Significantly better outcomes than standard Heparin
    1. Randomized trial (n=3171)
    2. Lower endpoint (death, Myocardial Infarction, Angina)
      1. 14 days (16.6 vs 19.8%)
      2. 20 days (19.8 vs 23.3%)
    3. Fewer revascularization procedures (27 vs 32.2%)
  2. Reference
    1. Cohen (1997) N Engl J Med 337:447-52 [PubMed]

VI. Efficacy

  1. Comparable efficacy to Heparin in DVT
  2. References
    1. Hull (2000) Arch Intern Med 160:229-36 [PubMed]
    2. Merli (2001) Ann Intern Med 134:191-202 [PubMed]

VII. Advantages: LMWH over Unfractionated Heparin

  1. Rarely causes Heparin Induced Thrombocytopenia
  2. Does not cause paradoxical thrombotic events
  3. Results in fewer bleeding complications
  4. References
    1. Warkentin (1995) N Engl J Med 332:1330-5 [PubMed]
    2. (1995) Arch Intern Med 155:601 [PubMed]

VIII. Dosing

  1. General
    1. Prophylaxis: Consider increasing the dose by 25% when BMI >40 kg/m2
    2. Treatment: Dose should be based on total body weight (even in obese patients)
    3. Exception: Fragmin has a maximum dose (unlike other LMWH agents)
    4. See specific preparation (e.g. Enoxaparin or Lovenox) for adjustments for Renal Function and Obesity
  2. Deep Vein Thrombosis Treatment
    1. Enoxaparin (Lovenox)
      1. Twice daily dosing: 1 mg/kg SQ twice daily
      2. Avoid once daily dosing of 1.5 mg/kg SQ daily (less effective, esp. in obese patients, and not for home)
      3. Available in 30 mg vials
    2. Tinzaparin (Innohep)
      1. Dose: 175 anti-Xa IU per kg daily
      2. Dose (ml): (weight in kg) x 0.00875 ml/kg daily
  3. Deep Vein Thrombosis Prophylaxis
    1. Ardeparin (Normiflo)
      1. Initial: 50 U/kg SQ following surgery
      2. Later: bid for 14 days or until ambulatory
    2. Dalteparin (Fragmin)
      1. Low risk
        1. Initial: 2500 IU SQ 1-2 hours before surgery
        2. Later: 2500 IU qd for 5-10 days
      2. High risk
        1. Initial: 5000 IU SQ the evening before surgery
        2. Later: 5000 IU qd for 5-10 days
    3. Danaparoid (Orgaran)
      1. Initial: 750 U SQ 1-4 hours before surgery
      2. Later: then 750 U SQ q12h for 7-10 days
    4. Enoxaparin (Lovenox)
      1. Initial: 30 mg SQ q12h OR 40 mg daily for 7-10 days
      2. Increase to 40 mg twice daily for obese patients
    5. Tinzaparin (Innohep)
      1. Innohep 3500 IU SQ daily

IX. Precautions

  1. Severe Renal Insufficiency
    1. Unpredictable dose response to LMWH
    2. CrCl <30 ml/min: See specific preparation regarding dosing (e.g. Enoxaparin or Lovenox)
    3. CrCl <15 ml/min: Use Unfractionated Heparin
  2. Obesity (BMI>40)
    1. Dosing frequency may need adjustment
    2. Lovenox has been studied at 1 mg/kg up to 190 kg
      1. For weights above this, follow anti-Xa levels
  3. Reversal
    1. Protamine
      1. Less responsive to Protamine compared with Heparin

X. References

  1. Zee (2017) Cochrane Database Syst Rev 8(8):CD006681 +PMID: 28780771 [PubMed]
  2. Robertson (2017) Cochrane Database Syst Rev 2(2):CD001100 +PMID: 28182249 [PubMed]

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