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Department of Anesthesiology, Virginia Commonwealth University Health System, Medical College of Virginia Campus, Richmond, VA
To the Editor:
Kieta et al. (1) described the use of argatroban anticoagulation for off-pump coronary artery bypass surgery in a patient with heparin-induced thrombocytopenia type II. While the case report and TEG data were interesting, based on our experience at Virginia Commonwealth University Health System, we believe that bivalirudin (Angiomax; The Medicines Company, Parsippany, NJ) offers a safer and more efficacious alternative for this case.
At our institution we have experienced success using bivalirudin anticoagulation for cardiac surgery both with and without cardiopulmonary bypass. Results awaiting publication from a trial of bivalirudin at our institution for cardiopulmonary bypass cases demonstrate equal or less chest tube drainage and blood utilization than standard heparin anticoagulation for cardiac surgery. Bivalirudin has a plasma half-life of 25 min (2), which is substantially shorter than argatroban, and a unique elimination method (from cleavage by thrombin) relatively independent of specific organ function (3). In patients with normal renal function, only 20% of the drug is cleared by kidneys while the rest is cleared by proteolysis. In dialysis patients or patients with severe renal impairment, the half-life is increased; however, excessive concentrations of bivalirudin can be effectively reduced by hemofiltration or plasmapheresis (2). Argatroban, which requires hepatic elimination, has been safely used in patients with renal failure (4).
In their report, Kieta et al. (1) stated, "no important clinical coagulopathy was noted." However, chest tube drainage for 24 h was 1186 mL, which we consider moderately severe postoperative bleeding for an off-pump CABG. Furthermore, the laboratory studies reported suggest evidence of coagulopathy as all coagulation parameters measured, except fibrinogen and platelets, were significantly elevated above baseline at 3 h after infusion.
The most significant finding in Kieta et al’s report is that at 3 h after infusion of argatroban, there remained marked prolongation of the ACT, aPTT, PT, and TEG R time, accompanied by a decrease in the TEG alpha angle and MA from baseline, suggesting a prolonged anticoagulant effect of argatroban. Given the relatively long half-life of argatroban (46 ± 10 min) and associated laboratory abnormalities, it appears likely that the excessive bleeding reported in the case was, at least in part, related to the residual effects of argatroban at the end of the case.
In summary, bivalirudin may offer a safer alternative for anticoagulation during cardiac surgery.
References
Department of Anesthesiology, The University of Alabama at Birmingham, Birmingham, Alabama
In Response:
Green et al. (1) contend that bivalirudin may be safer than argatroban for anticoagulation based on differences in half-life (25 versus 45 min, respectively) and based on the comparison of their institutional experience and pending study with our single-case report. At best, this is an untested hypothesis. Concerning the matter of half-life, a 20-min difference may be clinically unimportant in a setting such as coronary revascularization, where the etiology of hemorrhage is multifactorial. Furthermore, a comparison of their data with one case report is conceptually and statistically untenable—a fair comparison would be a prospective, double-blind comparison of the two antithrombotics in an appropriate setting.
While our patient experienced blood loss in the postoperative period, the majority of loss occurred in the first 2 h postinfusion. Furthermore, we remind our colleagues that our patient was 123 kg, so a blood loss of 400-500 mL over 2 h did not alarm us. By 3 h postinfusion, chest tube drainage decreased significantly in concordance with the restoration of coagulation parameters to near baseline values. Our contention that our patient did not experience clinically important coagulopathy was based on these data and the lack of allogeneic blood product administration.
Regarding the comment that "...at 3 h after infusion of argatroban, there remained marked prolongation of the ACT, aPTT, PT, and TEG R time, accompanied by a decrease in the TEG alpha angle and MA from baseline suggesting a prolonged anticoagulant effect...", we respond by presenting the data (1) in question for the readership’s convenience in table format (Table 1).
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In conclusion, patients with heparin-induced thrombocytopenia require heparin alternatives that are safe and effective. We presented a case report wherein argatroban was administered without morbidity with regard to hemodynamic or transfusion-based criteria. In the absence of a randomized, double-blind investigation comparing bivalirudin to argatroban in the setting of coronary revascularization, it is premature to claim that one antithrombotic is superior to the other for patients requiring a heparin alternative.
Reference
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