Bivalirudin in the Treatment of Patients with or at High-Risk for Heparin-Induced Thrombocytopenia.

Background: The management HIT in pts. with renal and/or hepatic impairment is problematic. Of the two DTI’s approved for HIT therapy in non-PCI settings, the utility of lepirudin is limited by renal impairment and argatroban is limited by hepatic impairment. In these settings, bivalirudin (BV), a hirudin analog primarily cleared by serum proteolysis and to a lesser extent, renally, has potential therapeutic advantages.

Objective: To describe the clinical/laboratory features, infusion parameters, and outcomes in BV-treated HIT pts.

Design: Retrospective case study.

Setting: Tertiary-care medical center, IRB-approved HIT Registry.

Participants: Twenty-five persons, 45–88 years of age with or at high-risk for HIT accrued from 2.1.03 to 4.30.06.

Baseline features: HIT developed in the following pt. cohorts: open heart surgery (n=21), medical (n=3), & vascular surgery (n=1). At HIT presentation, 10 had thrombocytopenia and 3 had active thromboembolic complications (TEC’s) (12 had both). The median platelet ct. was 82,500/mm³ (60% baseline decline). A (+) test for heparin-PF4 antibodies by ELISA (GTI) or HIPA was present in 24 (96%); 1 pt. (-) by both assays had a 32% platelet decline after 5 days on UFH. Prior DTI’s were administered in 11 (44%) with argatroban (n=9) or lepirudin (n=2) for a mean of 3.8 (0–10) days and 2.5 (1–4) days.

Results: At BV initiation, organ dysfunction by objective criteria was present in 16 (64%) pts.: hepatic insufficiency alone (6) or failure (8; 4 with renal failure); renal insufficiency or failure alone (1 each). The mean serum creatinine, total bilirubin and AST was 1.8 (0.8–4.1) mg/dl, 3.74 (0.3–12.1) mg/dl, and 309 (25–1102) U/L, respectively. Nine pts. required mechanical ventilation (4 with dialysis) and 19 pts. initiated BV in an ICU setting. BV was begun at a mean IV dose of 0.21 (0.05–0.50) mg/kg/h, adjusted to achieve an APTT 1.5–2.5× baseline, and maintained (n=24) at a mean IV dose of 0.20 (0.04–0.43) mg/kg/h. BV alone was continued for a mean of 8.5 (0–39) days. Seventeen pts. transitioned to warfarin after a mean BV overlap of 6.2 (1–38) days. The mean time to an initial therapeutic APTT was 15 (1.8–47) hours (46% with initial dose); mean dose adjustments: 1.4 (0–5) in 24 pts. The mean APTT and INR on BV alone was 65 sec and 1.46 (0.9–2.4); mean pre-BV INR: 1.27. The mean % of APTT’s/pt. (range; no. of APTT’s) within, below and above the therapeutic range were 60 (6–100; n=235) %, 10 (0–41; n=58) %, and 30 (0–94; n=100) %. Among 10/13 pts. with platelets <100,000/mm³ at BV initiation, the mean time to recovery ≥100,000/mm³ and ≥150,000/mm³ was 2.9 (1–6) days and 7.8 (3–18) days. Among 3/4 pts. with platelets ≥100,000/mm³ but <150,000/mm³, the mean time to recovery >150,000/mm³ was 2.7 (2–4) days. New TEC’s on BV developed in 3 pts. BV was discontinued in 8 pts. after a mean of 4.9 (1–10) days for evolving organ failure (n=4), bleeding (GI: n=2; open chest: n=1) and concern for drug half-life (n=1). Minor bleeding occurred in 3 pts. and 1 pt. required limb amputation prior to BV. Five pts. (20%) died from progressive HIT-related organ failure: 4 were off BV and received comfort care; 1 on BV with a therapeutic APTT unrelated to BV. The average length of hospitalization was 27 days (mean ICU stay: 17 days).

Conclusion: In this HIT patient cohort with predominantly hepatic and/or renal dysfunction, the administration of bivalirudin was effective in achieving an 80% survival rate with an acceptable safety profile.