Anti-Xa Levels in Critically Ill Patients Receiving Dalteparin for Thromboprophylaxis.

Abstract Rationale: Despite the efficacy and safety of low molecular weight heparin (LWMH) compared to unfractionated (UFH) in many patients, LMWH may bioaccumulate in patients with renal insufficiency which could cause an increased risk of bleeding. If LMWH thromboprophylaxis is safe in ICU patients with renal insufficiency, this could reduce the risk of DVT and HIT. Since the extent to which LMWH bioaccumulates in critically ill patients in prophylactic rather than therapeutic doses is unclear, our objective was to measure peak and trough anti-Xa levels during a multicenter randomized pilot trial of LMWH vs UFH for thromboprophylaxis in the medical-surgical ICU setting. Methods: We included 128 patients ≥18 years with an expected ICU stay ≥72h. We excluded patients with trauma, orthopedic, cardiac, or neurosurgery, severe hypertension, DVT, PE or hemorrhage within 3 mos, INR >2ULN, PTT >2ULN, platelets <100 x109/L, and if creatinine clearance was <30 ml/min on ICU admission. Trough anti-Xa levels were drawn when patients developed creatinine clearance <30ml/min, trough and peak anti-Xa levels were drawn on Tuesdays and Thursdays regardless of serum creatinine, and random anti-Xa levels were drawn if patients had a bleeding event. Results: No differences were found in the 2 groups (median anti-Xa levels) as shown below. Conclusions: We did not observe LWMH or UFH bioaccumulation when administered in prophylactic doses in these critically ill patients with a range of renal dysfunction. Anti-Xa Levels Allocation Cr Cl <30 (trough) Tues & Thurs (trough) Tues & Thurs (peak) Bleeding (random) Group A 8 tests in 2 pts 17 tests in 9 pts 17 tests in 9 pts 7 tests in 4 pts Group A 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL Group B 23 tests in 5 pts 46 tests in 12 pts 46 tests in 12 pts 10 tests in 8 pts Group B 0.1 IU/mL 0.09 IU/mL 0.11 IU/mL 0.1 IU/mL