Argatroban and renal replacement therapy in patients with heparin-induced thrombocytopenia.
BACKGROUND
Argatroban, a direct thrombin inhibitor, is an effective anticoagulant for patients who have heparin-induced thrombocytopenia (HIT). Anticoagulation is usually required for renal replacement therapy (RRT).


OBJECTIVE
To prospectively evaluate the pharmacokinetics, pharmacodynamics, and safety of argatroban during RRT in hospitalized patients with or at risk for HIT.


METHODS
Five patients with known or suspected HIT underwent hemodialysis (n = 4) or continuous venovenous hemofiltration (CVVH, n = 1), while receiving a continuous infusion of argatroban 0.5-2 microg/kg/min. Activated partial thromboplastin times (aPTTs), activated clotting times (ACTs), argatroban concentrations (plasma, dialysate, CVVH effluent), and safety were assessed before, during, and after a 4-hour session of RRT. Systemic and dialytic argatroban clearances were calculated.


RESULTS
Among the 4 hemodialysis patients, aPTT, ACT, and plasma argatroban concentrations remained stable during RRT, with respective mean +/- SD values of 74.3 +/- 34.2 seconds, 198 +/- 23 seconds, and 499 +/- 353 ng/mL before RRT, and 70.6 +/- 21.4 seconds, 181 +/- 12 seconds, and 453 +/- 295 ng/mL 2 hours after starting RRT (p values NS). Systemic clearance was 17.7 +/- 12.8 L/h before hemodialysis and 17.0 +/- 9.5 L/h during hemodialysis (n = 2). The dialyzer clearance (dialysate recovery method) was 1.5 +/- 0.4 L/h (n = 4). Generally similar responses occurred in the CVVH patient: systemic argatroban clearance was 4.8 L/h before CVVH and 4 L/h during CVVH. The hemofilter argatroban clearance was 0.9 L/h. No bleeding or thrombosis occurred.


CONCLUSIONS
Argatroban provides effective alternative anticoagulation in patients with or at risk for HIT during RRT. Argatroban clearance by high-flux membranes during hemodialysis and CVVH is clinically insignificant, necessitating no dose adjustment.
Tang
Ignatius Y
IY
Section of Nephrology, Department of Medicine, University of Chicago Hospitals, Chicago, IL 60637-1470, USA. itang@medicine.bsd.uchicago.edu
Cox
Donna S
DS
Patel
Kruti
K
Reddy
Bharathi V
BV
Nahlik
Linda
L
Trevino
Sharon
S
Murray
Patrick T
PT
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives; D005260:Female; D006493:Heparin / Q000009:adverse effects* / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D010875:Pipecolic Acids / Q000097:blood / Q000627:therapeutic use*; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000379:methods*; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000097:blood / Q000139:chemically induced* / Q000188:drug therapy*
D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban