What dose of Fragmin (Dalteparin) should I use for Deep Vein Thrombosis (DVT) prophylaxis in a patient with impaired renal function, specifically a serum creatinine level of 3.3 mg/dL?

Dalteparin (Fragmin) Dosing for DVT Prophylaxis in Renal Impairment

For a patient with a serum creatinine of 3.3 mg/dL requiring DVT prophylaxis, standard prophylactic dosing of dalteparin 5000 IU once daily can be used safely without dose adjustment, as dalteparin does not significantly bioaccumulate in severe renal impairment. 1

Dalteparin in Renal Impairment

Evidence Supporting Standard Dosing

• Prophylactic dalteparin (5000 IU daily) does not demonstrate significant bioaccumulation in patients with severe renal impairment (creatinine clearance <30 mL/min) 1, 2
• In a prospective study of critically ill patients with severe renal insufficiency receiving prophylactic dalteparin, no patient showed bioaccumulation (defined as trough anti-Xa level >0.40 IU/mL) 1
• Peak anti-Xa levels remained in a safe range (0.29-0.34 IU/mL) with trough levels <0.06 IU/mL, indicating no significant drug accumulation 1

Comparison with Other LMWHs

• Unlike enoxaparin, which requires dose adjustment in severe renal impairment, dalteparin at prophylactic doses can be used without dose adjustment 3
• Enoxaparin requires reduction to 30 mg once daily for prophylaxis in patients with creatinine clearance <30 mL/min due to increased bleeding risk 3
• Tinzaparin should be avoided in elderly patients (≥70 years) with renal insufficiency due to higher mortality rates observed in clinical trials 3

Monitoring Considerations

When to Monitor Anti-Xa Levels

• For prophylactic dosing of dalteparin in severe renal impairment, routine anti-Xa monitoring is not required 1, 2
• For therapeutic dosing in patients with cancer and creatinine clearance <30 mL/min, the manufacturer recommends monitoring peak anti-Xa levels 3, 4
• If monitoring is deemed necessary:
  • Target anti-Xa range for prophylaxis: 0.2-0.4 IU/mL 1
  • Measure anti-Xa levels 4-6 hours after injection 3
  • Obtain levels after the patient has received 3-4 doses of dalteparin 4

Safety Profile

• The incidence of major bleeding with prophylactic dalteparin in patients with severe renal impairment is not significantly increased compared to patients with normal renal function 1, 2
• In the DIRECT study, major bleeding occurred in 7.2% of patients with severe renal impairment receiving prophylactic dalteparin, but all had trough anti-Xa levels ≤0.18 IU/mL, suggesting bleeding was related to patient comorbidities rather than drug accumulation 2
• Risk factors for bleeding in renal impairment include concomitant aspirin use and elevated INR, not dalteparin accumulation 2

Clinical Decision Algorithm

1. Confirm renal impairment severity:

   • Calculate creatinine clearance (CrCl) using Cockcroft-Gault equation
   • Serum creatinine of 3.3 mg/dL likely corresponds to CrCl <30 mL/min

2. For DVT prophylaxis in this patient:

   • Administer dalteparin 5000 IU subcutaneously once daily 1
   • No dose adjustment is required despite severe renal impairment 1, 2

3. Monitor for:

   • Signs of bleeding (visible bleeding, decreasing hemoglobin)
   • Thrombocytopenia (check platelet count)
   • If platelets drop to 50,000-100,000/mm³, reduce dose by 2,500 IU 4
   • If platelets <50,000/mm³, discontinue dalteparin until recovery 4

4. Consider anti-Xa monitoring only if:

   • Patient has fluctuating renal function
   • Extreme body weight
   • Prolonged course of prophylaxis (>2 weeks)
   • Multiple risk factors for bleeding 3, 5

By following these guidelines, DVT prophylaxis can be safely administered with dalteparin in patients with severe renal impairment without increased risk of bleeding complications.