Bivalirudin

Initial dosing

Please use the following for the initial dose of bivalirudin in heparin-induced thrombocytopenia (HIT):

Creatinine Clearance (CrCl)	T 1/2	Recommended initial infusion rate (based on total body weight)
>60 ml/min	25 minutes	0.15 mg/kg/hr
30-60 ml/min	34 minutes	0.08 mg/kg/hr
<30 ml/min	57 minutes	0.05 mg/kg/hr
Dialysis-dependent patients (off dialysis)	3-5 hours	0.05 mg/kg/hr*
Dialysis-dependent patients (on dialysis)	(25% clearance by HD filters)	0.05 mg/kg/hr*

*Based on a review of internal data as well as most recent literature, patients receiving renal replacement therapy are now recommended to start bivalirudin at a rate of 0.05 mg/kg/hr (previously 0.02 mg/kg/hr).

References

Tsu LV and Dager WE. Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia. Ann Pharmacother 2011; 45(10):1185-92.

Runyan CL et al. Correlation of bivalirudin dose with creatinine clearance during treatment of heparin-induced thrombocytopenia. Pharmacotherapy 2011; 31(9):850-6.

Kiser TH et al. Safety, efficacy and dosing requirements of bivalirudin patients with heparin-induced thrombocytopenia. Pharmacotherapy 2008; 28:1115-24

Therapeutic Monitoring

At UWMC, bivalirudin is monitored using the Direct Thrombin Inhibitor (DTI) assay (Plasma-Diluted Thrombin Time).

Used instead of aPTT to monitor injectable DTI therapy. Preferred over aPTT due to better sensitivity, and is not affected by antiphospholipid antibodies. Cost, turnaround time, and 24/7 availability at UWMC are similar to aPTT. (Source)

Therapeutic range for DTIs administered by continuous infusion
- For argatroban: 60-100 seconds
- For bivalirudin: 60-90 seconds
- For lepirudin: 90-160 seconds
Test order code: DTI
Specimen collection: 3mL or 5mL blue top

Dosing Algorithm

For patients with confirmed or suspected heparin-induced thrombocytopenia (HIT). (Download PDF of Chart)

(DTI Goal: 60-90 seconds)

DTI Assay	Dose Adjustment	Calculation	Next DTI
< 60	Increase infusion rate by 20%	New Rate = current rate x 1.2 [example: current rate 0.15 mg/kg/hr x 1.2 = new rate 0.18 mg/kg/hr]	2 hours
60-90 (Goal)	NO CHANGE	NO CHANGE	2 hours x 1, then q AM
> 90	Hold infusion for 1 hour, then restart at 50% less than the previous rate	New rate = current rate x 0.5 [example: current rate 0.15mg/kg/hr x 0.5 = new rate 0.075 mg/kg/hr]	2 hours

Monitoring Warfarin While on Bivalirudin

Bivalirudin elevates prothrombin time/INR. For an accurate assessment of warfarin effect in patients on current bivalirudin, use Chromogenic Factor X monitoring.

Chromogenic Factor X

Used instead of INR to monitor warfarin in patients bridged with direct thrombin inhibitors that might interfere with INR.

In rare cases, strong lupus inhibitor/antiphospholipid antibodies might also interfere with PT/INR, in which case chromogenic factor X levels may be used as an alternative monitoring strategy. If there is a concern for an inhibitor, a PT 1:1 mixing study can help determine if an inhibitor is present. Otherwise, INR should be used as the default monitoring strategy. For patients with newly diagnosed APS treated with warfarin, INR values (measured on the OUTPATIENT instrument that will be used for chronic treatment) should be checked for correlation with factor X activity.

Therapeutic range for warfarin:
- CFX 35-25% = INR 2-4
Test order code: CHRF10
Specimen collection: 3mL or 5mL light top tube (citrate)