II. Indications

III. Mechanism

  1. See Intrinsic Clotting Pathway
  2. 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

IV. Dosing: Prophylactic for DVT Prevention

  1. Heparin 5000 Units SQ every 8-12 hours

V. Dosing: Adult High Intensity Dosing by Weight based Calculations (PE/DVT)

  1. Measure
    1. Total body weight (TBW) in kilograms
    2. Height in inches
  2. Calculate Lean Body Weight (LBW) in kilograms
    1. Male: 50 + 2.3 x (height in inches - 60)
    2. Female: 45 + 2.3 x (height in inches -60)
  3. Calculate Dosing Weight
    1. Non-Obese
      1. Dosing Weight (kg): TBW above
    2. Obese (TBW > 1.4 x LBW)
      1. Dosing Weight (kg): (0.4 x TBW) + LBW
  4. Calculate Heparin starting doses
    1. Monitor with aPTT
    2. Bolus: 80 Units/kg
      1. Maximum: 10,000 units
      2. Round to nearest 100 units
    3. Maintenance: 18 Units/kg/hour
      1. Round to nearest 50 units per hour
  5. Alternative Protocol in an unmonitored setting (off label)
    1. Load 333 units/kg SC
    2. Maintenance 250 units/kg SC every 12 hours
    3. Maximum weight 100 kg
  6. Pregnancy
    1. Continue above protocol for at least 5 days of full Anticoagulation
    2. Next, administer 10,000 units SC every 8 to 12 hours adjusting based on aPTT target 1.5 to 2.5x normal control
    3. Transition back to Heparin infusion, at least 24 hours before delivery

VI. Protocol: Adult High Intensity Therapeutic Dosing Nomogram Using PTT (PE/DVT)

  1. Alternatively, use Anti-Xa Level for monitoring
  2. Protocol follows high intensity starting dose as above
  3. aPTT <35 seconds (<1.2x normal control)
    1. Give 80 units/kg IV bolus
    2. Increase infusion rate by 4 units/kg/hour
    3. Recheck aPTT in 6 hours
  4. aPTT 35 to 45 seconds (1.2 to 1.5x normal control)
    1. Give 40 units/kg IV bolus
    2. Increase infusion rate by 2 units/kg/hour
    3. Recheck aPTT in 6 hours
  5. aPTT 46 to 70 seconds (1.5 to 2.3x normal control)
    1. No change in dosing
    2. Recheck aPTT on the next morning
  6. aPTT 71 to 90 seconds (2.3 to 3.0x normal control)
    1. Decrease maintenance rate by 2 units/kg/hour
    2. Recheck aPTT in 6 hours
  7. aPTT >90 seconds
    1. Stop Heparin infusion for 60 minutes
    2. Decrease maintenance rate by 3 units/kg/hour
    3. Recheck aPTT in 6 hours

VII. Dosing: Child High Intensity Dosing by Weight based Calculations (PE/DVT)

  1. Monitor and adjust infusion based on aPTT or anti-Xa Levels
  2. Starting Protocol 1 (FDA approved package insert)
    1. Bolus 50 units/kg IV
    2. Maintenance: 25 Units/kg/hour
  3. Starting Protocol 2 (off label)
    1. Bolus 75 units/kg IV over 10 minutes
    2. Maintenance: 20 Units/kg/hour
      1. Start 28 units/kg/hour if age <1 year old

VIII. Dosing: Adult Low Intensity Dosing by Weight-Based Calculations (Acute Coronary Syndrome)

  1. Monitor and adjust infusion based on aPTT (1.5 to 2x normal) or anti-Xa Levels
  2. Load 60 units/kg IV (up to 4000 units IV)
  3. Infuse 12 units/kg/hour

IX. Labs: Therapeutic Dosing Initial (before Heparin)

  1. Partial Thromboplastin Time (aPTT)
  2. Anti-Xa Level (if used instead of aPTT)
  3. ProTime (INR)
  4. Complete Blood Count (CBC) with Platelet Count

X. Labs: Therapeutic Dosing Recurring Labs

  1. Partial Thromboplastin Time (aPTT)
    1. 6 hours after bolus and then per nomogram
  2. Anti-Xa Level
    1. May be used as an alternative to aPTT monitoring
  3. Platelets
    1. Every 3 days
    2. Minimum: 150,000

XI. Adverse Effects

  1. Bleeding complications
  2. Heparin Induced Thrombocytopenia

XII. Drug Interactions

  1. Medications that increase bleeding risk
    1. Aspirin
    2. Platelet ADP Receptor Antagonist (e.g. Clopidogrel)
    3. NSAIDs (e.g. Ibuprofen, Indomethacin)
    4. Other Anticoagulants (e.g. DOACs, Warfarin)
    5. Glycoprotein IIB/IIIA Inhibitor
    6. Miscellaneous antibiotics (e.g. some Penicillins, Cephalosporins)
    7. Valproic Acid
    8. AntiThyroid Medications (Methimazole, Propylthiouracil)
    9. Antimalarials (Chloroquine, Hydroxychloroquine)
  2. Medications that decrease Heparin efficacy
    1. Digoxin
    2. Tetracycline
    3. Antihistamines

XIII. Management: Reversal

  1. Protamine sulfate

XV. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 83
  3. Warnock (2022) Heparin, StatPearls, Treasure Island, FL
    1. https://www.ncbi.nlm.nih.gov/books/NBK538247/

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heparin (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
HEPARIN SODIUM 10,000 UNIT/ML VIAL Generic $1.79 per ml
HEPARIN SODIUM 5,000 UNIT/ML VIAL Generic $1.30 per ml