BLEEDING COMPLICATIONS ASSOCIATED WITH R-HIRUDIN APPLICATION FOR CARDIOPULMONARY BYPASS IN PATIENTS WITH HEPARIN-INDUCED THROMBOCYTOPENIA TYPE II

Abstract

Introduction. Heparin-induced thrombocytopenia type II is a severe complication following exposure to heparins [1]. Therefore, alternative anticoagulation is mandatory for these patients. Among contemporary options for CPB (e.g., the heparinoid orgaran, defibrinogenation with ancrod, or platelet inhibitors), the direct thrombininhibitor r-hirudin has been reported superior because of several important issues [2,3]: (1) immediate onset of action; (2) fast renal elimination (ca. 60 min); (3) no cross-reaction with heparin-induced antibodies; and (4) comprehensive on-line monitoring applying the ecarin clotting time (ECT). However, as with other options, the actual lack of an adequate reversal agent is one of the major disadvantages. Additionally, only few information is available concerning adverse effects of r-hirudin application during CPB, particularly regarding potential bleeding complications due to the unavailability of a reversal agent. Methods. 21 patients with HIT II and cross-reactivity to unfractioned heparins and danaparoid sodium (orgaran) underwent emergent cardiac surgery (anginal symptoms, S-T-elevations). R-hirudin (Refludan[registered sign], Hoechst, Frankfurt, Germany) application consisted of a bolus of 0.25 mg/kgBW given prior cannulation, 0.20 mg/kgBW added to the prime, and repetitive boli of 5 mg to maintain r-hirudin levels between 3 - 4 [micro sign]g/mL (modified according to the Poetzsch regimen [2,3]). The concentrations of r-hirudin were measured in citrated whole blood applying the ECT (TAS analyzer; Cardiovascular Diagnostics, Inc., Raleigh, NC, USA). Results. In 16 of the total of 21 patients, the postoperative drainage was limited to 100 - 800 mL. Of these, no patient developed renal failure. In 5 patients, postoperative blood loss exceeded 1,200 mL. Among these, 4 patients required surgical reexploration: one patient had undergone preoperative dialysis, and the three other patients developed early postoperative renal insufficiency due to cardiac failure). Surgical problems (e.g., diffuse bleeding and oozing) were identified as the major reasons for the bleeding complications. However, blood loss was found to increase along with the increasing r-hirudin concentrations caused by an r-hirudin rebound associated with renal failure. Discussion. Employment of r-hirudin for anticoagulation during CPB in patients with HIT II is safe provided a non-impaired renal function. However, impairment of renal function is associated with a r-hirudin rebound causing increased bleeding complications. In these patients, early perioperative augmentation of renal elimination by hemofiltration should be considered.