Fragmin (Dalteparin) Management in Renal Impairment
Dalteparin is the preferred low-molecular-weight heparin for patients with severe renal insufficiency (CrCl <30 mL/min) because it does not demonstrate clinically significant bioaccumulation at prophylactic doses and can be used therapeutically with anti-Xa monitoring, unlike enoxaparin which requires mandatory dose reduction and carries 2-3 fold increased bleeding risk. 1, 2
Prophylactic Dosing in Renal Impairment
Standard Prophylactic Dose
- Administer dalteparin 5,000 IU subcutaneously once daily for VTE prophylaxis, regardless of renal function 2, 3
- No dose adjustment is required even in severe renal insufficiency (CrCl <30 mL/min) for prophylactic dosing 1, 4
- Peak anti-Xa levels remain between 0.29-0.34 IU/mL in patients with severe renal impairment, well below therapeutic range 5, 3
Evidence Supporting Safety
- A multicenter trial of 138 critically ill patients with CrCl <30 mL/min (mean 18.9 mL/min) receiving dalteparin 5,000 IU daily showed zero cases of bioaccumulation (0%; 95% CI: 0%-3.0%) over a median 7 days of treatment 3
- Prospective cohort studies demonstrate no bioaccumulation >30% even after 10-20 days of prophylactic dosing in severe renal insufficiency 4, 6
- Major bleeding occurred in only 7.2% of critically ill patients with severe renal impairment, all with trough anti-Xa levels ≤0.18 IU/mL 3
When to Monitor Anti-Xa Levels for Prophylaxis
Anti-Xa monitoring is NOT routinely required for prophylactic dosing, even in severe renal impairment 1, 4. However, consider monitoring if:
- Prolonged prophylaxis >2 weeks is anticipated 1
- Fluctuating renal function is present 1
- Multiple bleeding risk factors coexist 1
Therapeutic Dosing in Renal Impairment
Standard Therapeutic Dose (CrCl ≥30 mL/min)
- Month 1: 200 IU/kg subcutaneously once daily 2, 7
- Months 2-6: 150 IU/kg subcutaneously once daily (see weight-based table below) 2
Weight-Based Dosing for Months 2-6
| Body Weight | Dalteparin Dose |
|---|---|
| ≤56 kg | 7,500 units once daily |
| 57-68 kg | 10,000 units once daily |
| 69-82 kg | 12,500 units once daily |
| 83-98 kg | 15,000 units once daily |
| ≥99 kg | 18,000 units once daily |
| [2] |
Severe Renal Impairment (CrCl <30 mL/min)
For therapeutic anticoagulation in patients with CrCl <30 mL/min, mandatory anti-Xa monitoring is required 2, 5:
- Use the same weight-based dosing as above initially 7
- Target anti-Xa range: 0.5-1.5 IU/mL 2, 5
- Measure peak anti-Xa levels 4-6 hours after the 3rd or 4th dose 2, 1
- Monitor anti-Xa levels twice weekly during the first month, then every 1-2 weeks during extended therapy 1
Clinical Evidence in Renal Impairment
- Post hoc analysis of the CLOT study showed dalteparin reduced recurrent VTE by 85% compared to warfarin in cancer patients with renal impairment (CrCl <60 mL/min): 2.7% vs 17.0%, HR 0.15 (95% CI 0.03-0.65, p=0.01) 7
- Bleeding rates were similar between dalteparin and warfarin in patients with renal impairment (p=0.47) 7
Critical Comparison with Other Anticoagulants
Why NOT Enoxaparin
Enoxaparin should be avoided in severe renal impairment because:
- Requires mandatory dose reduction to 1 mg/kg once daily for treatment and 30 mg once daily for prophylaxis when CrCl <30 mL/min 8, 1
- Carries 2-3 fold increased bleeding risk without dose adjustment 8
- Enoxaparin clearance decreases by 44% in severe renal impairment 8
Why NOT Tinzaparin
Tinzaparin should be avoided in elderly patients (≥70 years) with renal insufficiency 5, 1:
- Associated with significantly higher mortality compared to unfractionated heparin (11.2% vs 6.3%, p=0.049) in elderly patients with CrCl <60 mL/min 5
- Clinical trial was terminated early due to safety concerns 5
Why NOT Fondaparinux
Fondaparinux is absolutely contraindicated when CrCl <30 mL/min 9, 8:
- Complete renal elimination with prolonged half-life (17-21 hours) leads to inevitable accumulation 9
- No reversal agent available 9
- Never use in dialysis patients 8
Special Populations and Dosing Adjustments
Obesity (BMI ≥40 kg/m²)
- For prophylaxis: Consider increasing to dalteparin 5,000 IU twice daily or measuring anti-Xa activity 5
- For treatment: Use standard weight-based dosing (200 IU/kg then 150 IU/kg), but consider anti-Xa monitoring if BMI >40 5
- Prophylaxis with 5,000 IU once daily was ineffective in patients with BMI ≥40 kg/m² 5
Underweight Patients (BW <50 kg)
- Use standard weight-based dosing for treatment 2
- Consider anti-Xa monitoring for severe underweight (<40 kg) 5
- Caution advised due to increased bleeding risk 5
Thrombocytopenia
Dose reduction algorithm 2:
- Platelet count ≤50,000/mm³: Discontinue dalteparin until platelets >50,000/mm³
- Platelet count 50,000-100,000/mm³: Reduce daily dose by 2,500 units until platelets ≥100,000/mm³
Administration Technique
Subcutaneous Injection Protocol
- Inject in U-shaped area around navel, upper outer thigh, or upper outer buttock 2
- Vary injection site daily 2
- Insert entire needle length at 45-90 degree angle 2
- Do NOT expel air bubble from prefilled syringe before injection to ensure full dose delivery 2
- Lift skin fold with thumb and forefinger during injection 2
Critical Safety Warnings
- Never administer intramuscularly 2
- Latex allergy: Prefilled syringes contain natural rubber latex in needle shield 2
- Multiple-dose vials contain benzyl alcohol (14 mg/mL); use preservative-free formulations in neonates whenever possible 2
Common Pitfalls to Avoid
Do NOT switch between anticoagulants mid-treatment (e.g., dalteparin to enoxaparin or UFH), as crossover significantly increases bleeding risk 9
Do NOT use prophylactic dosing for therapeutic indications in obese patients (BMI ≥40), as 5,000 IU once daily is inadequate 5
Do NOT assume all LMWHs behave similarly in renal impairment—dalteparin has the most favorable safety profile 1, 7
Do NOT delay anti-Xa monitoring in severe renal impairment receiving therapeutic doses—measure after 3-4 doses, not on day 1 2
Recognize the single case report of life-threatening hemorrhage in an 84-year-old with chronic renal failure receiving dalteparin, though this occurred before modern monitoring protocols were established 10