What are the indications for intravenous (IV) heparin versus subcutaneous (SC) heparin, such as enoxaparin (enoxaparin sodium) or dalteparin (dalteparin sodium), in the treatment of large venous thrombophlebitis?

Treatment of Large Venous Thrombophlebitis: IV vs SC Heparin

For large venous thrombophlebitis (proximal deep vein thrombosis), subcutaneous low-molecular-weight heparin (LMWH) is preferred over both intravenous and subcutaneous unfractionated heparin, with intravenous unfractionated heparin reserved only for specific high-risk situations requiring rapid reversal or when subcutaneous absorption is unreliable. 1

Primary Recommendation: LMWH as First-Line Therapy

The American College of Chest Physicians guidelines establish a clear hierarchy for treating acute DVT:

• LMWH (enoxaparin or dalteparin) is preferred over IV unfractionated heparin (Grade 2C) and over subcutaneous unfractionated heparin (Grade 2B) 1
• Enoxaparin 1 mg/kg subcutaneously twice daily or 1.5 mg/kg once daily is the clinical standard for outpatient DVT treatment 1
• Dalteparin 200 IU/kg subcutaneously once daily is an equivalent alternative 1
• Once-daily dosing is preferred over twice-daily administration (Grade 2C) 1

Key Advantages of LMWH Over Unfractionated Heparin

• Lower risk of heparin-induced thrombocytopenia (HIT): LMWH carries significantly lower HIT risk compared to UFH (which can be as high as 5%), eliminating the need for routine platelet monitoring in most patients 1
• No laboratory monitoring required: Unlike IV heparin requiring aPTT checks every 4 hours, LMWH requires no routine coagulation monitoring 1, 2
• Outpatient treatment feasible: Simple subcutaneous administration allows home treatment in 68-72% of patients 3
• Equal or superior efficacy: Clinical trials demonstrate equivalent recurrence rates (3.4-3.8%) with comparable or lower bleeding rates 3, 4

Specific Indications for IV Unfractionated Heparin

IV heparin should be reserved for the following clinical scenarios:

1. Hemodynamically Unstable Patients

• Patients with massive PE causing hypotension (systolic BP <90 mmHg) where thrombolytic therapy is being considered or planned 1
• Situations requiring immediate, titratable anticoagulation with rapid reversibility 1

2. Concerns About Subcutaneous Absorption

• Severe peripheral edema or anasarca where subcutaneous bioavailability is questionable 1
• Shock states with poor peripheral perfusion 1

3. Severe Renal Impairment

• Creatinine clearance <30 mL/min where LMWH accumulation is a concern 1
• IV UFH is preferred as it's primarily metabolized by the liver, not renally excreted 1

4. Need for Rapid Reversal

• Patients at extremely high bleeding risk or requiring urgent procedures where protamine reversal may be needed 2
• Active bleeding requiring immediate anticoagulation cessation 2

Subcutaneous Unfractionated Heparin: A Middle Ground

Fixed-dose weight-adjusted subcutaneous UFH is an acceptable alternative when LMWH is unavailable or contraindicated:

• Initial dose: 333 U/kg subcutaneously, followed by 250 U/kg every 12 hours 3
• Demonstrated equivalent efficacy to LMWH (recurrence rate 3.8% vs 3.4%) 3
• Suitable for outpatient treatment in 72% of patients 3
• However, still carries higher HIT risk than LMWH, requiring platelet monitoring every 2-3 days from day 4 to day 14 1

Dosing Algorithms

For LMWH (Preferred)

• Enoxaparin: 1 mg/kg SC twice daily OR 1.5 mg/kg SC once daily 1
• Dalteparin: 200 IU/kg SC once daily (maximum 18,000 IU) 1
• Continue for minimum 5 days AND until INR ≥2.0 for at least 24 hours if transitioning to warfarin 1

For IV Unfractionated Heparin (When Indicated)

• Loading dose: 80 U/kg IV bolus (or fixed 5,000 units) 2, 5
• Maintenance: 18 U/kg/hour continuous infusion (approximately 30,000-40,000 units/24 hours) 2, 5, 6
• Target aPTT: 1.5-2.5 times control (typically 50-90 seconds) 2, 7
• Monitoring: Check aPTT at 4 hours, then every 4 hours until stable, then daily 2

For SC Unfractionated Heparin (Alternative)

• Initial: 333 U/kg SC, followed by 250 U/kg SC every 12 hours 3
• Monitoring: aPTT drawn 4-6 hours after injection, target 1.5-2.5 times control 2, 7

Critical Pitfalls to Avoid

• Do not use prophylactic doses for treatment: Therapeutic anticoagulation requires full-dose regimens; inadequate initial anticoagulation (aPTT <1.5 times control) is associated with 25% recurrence risk 5
• Do not give IV heparin intramuscularly: This route causes frequent hematomas and is contraindicated 2
• Do not forget renal dosing adjustments: In CrCl <30 mL/min, reduce enoxaparin to 1 mg/kg once daily or use IV UFH instead 1
• Do not skip platelet monitoring with UFH: Check platelets every 2-3 days from day 4-14 when using any form of unfractionated heparin 1
• Do not delay warfarin initiation: Start warfarin on day 1 of heparin therapy, not after heparin is stopped 1

Special Populations

Cancer Patients

• LMWH is strongly preferred over warfarin for extended therapy (Grade 2B) 1
• Dalteparin demonstrated superior efficacy (4% vs 11% recurrence) in cancer patients 1

Pregnancy

• LMWH is the anticoagulant of choice throughout pregnancy 1
• Warfarin is contraindicated; IV or SC UFH are alternatives if LMWH unavailable 1

Obesity

• Consider weight-based dosing without capping maximum doses for LMWH 1
• Anti-Xa monitoring may be considered in extreme obesity (BMI >40), though not routinely required 1