What is the duration of action of heparin (Unfractionated Heparin (UFH) / Low Molecular Weight Heparin (LMWH))?

Duration of Action of Heparin (UFH and LMWH)

Unfractionated heparin (UFH) has a short half-life of 0.5 to 2 hours, while low molecular weight heparin (LMWH) has a longer half-life of approximately 4-6 hours, resulting in more predictable anticoagulation effects. 1

Pharmacokinetics of Unfractionated Heparin (UFH)

UFH has several key characteristics that determine its duration of action:

• Half-life: 0.5 to 2 hours, dose-dependent 1
• Clearance mechanism: Biphasic clearance
  • Rapid saturable clearance (zero-order process due to binding to proteins, endothelial cells, and macrophages)
  • Slower first-order elimination 1
• Distribution: Primarily intravascular with volume of distribution of 0.07 L/kg 1
• Binding: Highly bound to antithrombin, fibrinogens, globulins, serum proteases, and lipoproteins 1
• Metabolism: Does not undergo enzymatic degradation 1
• Elimination: Primarily cleared by liver and reticuloendothelial cells 1

Clinical Implications for UFH

• Monitoring: Requires frequent monitoring (every 6 hours after dose changes) until therapeutic levels are achieved 2
• Therapeutic effect: When two consecutive aPTT values are therapeutic, measurements may be made every 24 hours 2
• Target range: For therapeutic dosing, target anti-Xa level of 0.5-0.7 IU/mL is recommended 2
• Duration of therapy: Most trials evaluating UFH in acute coronary syndromes continued therapy for 2 to 5 days 2

Pharmacokinetics of Low Molecular Weight Heparin (LMWH)

LMWHs have distinct advantages over UFH:

• Predictability: More predictable dose-response than UFH 2
• Bioavailability: Higher bioavailability after subcutaneous administration
• Binding: Less binding to plasma proteins and endothelial cells 2
• Clearance: Primarily renal elimination (dose-independent) 3
• Monitoring: Generally does not require routine laboratory monitoring 2

Clinical Implications for LMWH

• Duration of effect: Single dose typically provides 12-24 hours of anticoagulation 2
• Monitoring: For intermediate and therapeutic doses, monitoring peak anti-Xa level (4 hours after third injection) is suggested to avoid overdose 2
• Overdose threshold: Anti-Xa level defining overdose differs by molecule (e.g., 1.5 IU/mL for enoxaparin or tinzaparin) 2
• Renal function: LMWHs with less dependent renal elimination (tinzaparin or dalteparin) may be considered in patients with renal impairment 2

Special Populations

Elderly Patients

• Patients over 60 years may have higher plasma levels of heparin and longer aPTTs compared with younger patients given similar doses 1

Renal Impairment

• For patients with severe renal insufficiency (CrCl <30 mL/min), LMWH dose should be reduced or UFH considered 4

Common Pitfalls and Caveats

1. Delayed anticoagulation effect: Failure to recognize the short half-life of UFH can lead to subtherapeutic anticoagulation if doses are missed or delayed

2. Monitoring errors: Delays in laboratory turnaround time for aPTT results can lead to over- or under-anticoagulation for prolonged periods 2

3. Heparin-induced thrombocytopenia (HIT):

   • Mild thrombocytopenia occurs in 10-20% of patients receiving heparin
   • Significant thrombocytopenia (platelet count <100,000) occurs in 1-5% of patients, typically after 4-14 days of therapy
   • Autoimmune UFH-induced thrombocytopenia with thrombosis is rare (<0.2%) but dangerous 2

4. Rebound hypercoagulability: Abrupt discontinuation of heparin, particularly UFH, may lead to rebound hypercoagulability

5. Failure to recognize drug interactions: Both UFH and LMWH can interact with other medications affecting coagulation

Algorithmic Approach to Heparin Duration Management

1. For UFH:

   • Initial duration: 2-5 days for most indications 2
   • Monitor aPTT every 6 hours after dose changes until therapeutic
   • Once stable (2 consecutive therapeutic aPTTs), monitor every 24 hours
   • For transitioning to oral anticoagulants: Overlap for 5-7 days minimum 2

2. For LMWH:

   • Standard prophylactic duration:
     • Hospitalized medical patients: Until discharge or fully ambulatory 2
     • Surgical patients: At least 7-10 days 2
     • High-risk surgical patients: Consider extended prophylaxis for up to 4 weeks 2
   • Therapeutic duration:
     • Acute VTE: Initial treatment for at least 5 days when transitioning to oral anticoagulants 2
     • Cancer-associated thrombosis: At least 6 months 2

By understanding the pharmacokinetic differences between UFH and LMWH, clinicians can optimize anticoagulation therapy while minimizing risks of both thrombotic and bleeding complications.