Correlation of bivalirudin dose with creatinine clearance during treatment of heparin-induced thrombocytopenia.

Study Objectives: To evaluate steady-state bivalirudin dosing requirements in patients with a wide range of kidney function who were being treated for heparin-induced thrombocytopenia (HIT)-related disorders.

Design: Retrospective medical record review.

Setting: Academic medical center.

Patients: Sixty-four adults with varying degrees of renal function who were receiving bivalirudin for at least 48 hours for HIT-related disorders between March 2007 and May 2010.

Measurements And Main Results: Steady-state conditions were defined as a constant bivalirudin infusion dose for at least 12 hours, with serum creatinine concentration varying less than 20% for 48 hours (for patients not receiving renal replacement therapy) and at least two therapeutic activated partial thromboplastin time (aPTT) values (60-80 sec). Patients were assigned to five groups based on Cockcroft-Gault-estimated creatinine clearance (Clcr) of less than 30, 30-60, or greater than 60 ml/minute, or by type of renal replacement therapy-intermittent hemodialysis or continuous venovenous hemofiltration (CVVH). For Clcr greater than 60 ml/minute, the median bivalirudin dose was 0.15 mg/kg/hour (interquartile range [IQR] 0.11-0.15 mg/kg/hr), which was greater than median doses for Clcr 30-60 ml/minute (0.10 mg/kg/hr, IQR 0.06-0.13 mg/kg/hr, p=0.004), Clcr less than 30 ml/minute (0.08 mg/kg/hr, IQR 0.04-0.1 mg/kg/hr, p=0.001), CVVH (0.06 mg/kg/hr, IQR 0.03-0.10 mg/kg/hr, p=0.046), and hemodialysis (0.04 mg/kg/hr, IQR 0.03-0.05 mg/kg/hr, p=0.0001). Bivalirudin doses correlated with Clcr (Spearman r = 0.58, p<0.01). The median aPTT value of 70 seconds (IQR 63-74 sec) was similar in all groups. Thrombosis was present before bivalirudin therapy in 18 (28%) of 64 patients, and two patients (3%) developed thromboemboli during bivalirudin therapy. Clinically significant bleeding related to bivalirudin and leading to discontinuation of bivalirudin occurred in four patients (6%). The median international normalized ratio increased from 1.5 (IQR 1.3-1.7) before bivalirudin therapy to 1.9 (IQR 1.8-2.1) during bivalirudin therapy (p=0.002) in 11 patients who were not receiving warfarin.

Conclusion: Bivalirudin dosing requirements increased with increasing Clcr values. The high degree of variability suggests that dosing in individual patients will require careful titration to achieve adequate anticoagulation.