Original Articles
Recombinant hirudin as an alternative for anticoagulation during cardiopulmonary bypass in patients with heparin-induced thrombocytopenia type II: A 1-year experience in 57 patients*

https://doi.org/10.1053/cr.2000.5861Get rights and content

Abstract

Objective: To explore the possible use of recombinant hirudin (r-hirudin) as an alternative to heparin for anticoagulation during cardiovascular surgery. Design: Retrospective analysis. Setting: Two university hospitals. Participants: Fifty-seven patients with heparin-induced thrombocytopenia type II (HIT II) in whom r-hirudin was used during cardiovascular surgery with cardiopulmonary bypass (CPB). Interventions: None. Measurements and Main Results: The r-hirudin concentration was monitored on-line, at the point of the patient's care using the ecarin clotting time and maintained in the range of 3 to 4 μg/mL. The r-hirudin elimination at the conclusion of CPB was augmented through modified zero-balanced ultrafiltration and forced diuresis. The duration of CPB was 63 to 246 minutes. The r-hirudin requirement per minute of CPB was 0.016 to 0.035 μg/kg/min, and the 24-hour blood drainage was 50 to 2,200 mL. Of the 57 patients, 54 fully recovered, including 9 patients who did not require any allogenic products. Four patients, all with impaired renal function, showed prolonged r-hirudin elimination and excessive bleeding and required surgical reexploration. Three patients died as a result of complications unrelated to the perioperative management. Conclusion: This study provides evidence that r-hirudin can be used safely and effectively for routine anticoagulation during CPB in patients diagnosed with HIT II. Almost 95% of the patients in whom it was used were discharged uneventfully. Patients with perioperative renal failure, however, showed increased bleeding. Copyright © 2000 by W.B. Saunders Company

Section snippets

Methods

The present study comprised a series of patients admitted for surgery between June 1997 (r-hirudin was approved by European regulatory authorities in May 17, 1997) and July 1998 (U.S. Food and Drug Administration approval). Within this period, 6,733 cardiac surgeries were performed. Of these, 57 patients (0.8%) requiring CPB were anticoagulated with r-hirudin instead of heparin.

Evidence of heparin-induced thrombocytopenia type II and cross-reactivity to orgaran

Of the 57 patients, 44 had a history of single or recurrent thromboembolic complications when previously hospitalized, and 16 patients had been diagnosed for HIT II (ie, HIPAA, PF 4 ELISA, clinical signs) (Table 1). Thirty-two patients were admitted with a platelet count less than 100 × 103/μL, and 10 patients developed a marked (>30%) decrease in platelet count during the administration of heparin (from 221 ± 72 × 103/μL to 43 ± 12 × 103/μL) (Table 1). In 46 patients, the HIPAA yielded a

Discussion

The development of a recombinant preparation for hirudin, r-hirudin, has facilitated the introduction of this anticoagulant into clinical practice. This agent is advantageous for use in patients with HIT II, because it is unreactive with HIT II—related antibodies and can be reliably monitored using the ECT.7, 12, 13, 14, 15, 17 The present study shows in a relatively large group of patients that r-hirudin is safe and effective for high-dose systemic anticoagulation during CPB in patients with

Acknowledgements

The authors are grateful to Mrs. Tony Derwent, for reviewing and editing the manuscript.

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    *

    Address reprint requests to Fritz Mertzlufft, MD, PhD, Klinik fuer Anaesthesiologie und Intensivmedizin, Universitaetskliniken des Saarlandes, D-66421 Homburg/Saar, Germany.

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