Re-evaluation of the role of antifibrinolytic therapy with lysine analogs during cardiac surgery in the post aprotinin era

Abstract

The lysine analogs are unspecific enzyme inhibitors. Therefore, it is conceivable that an overdosing might reveal severe clinical side-effects beyond the inhibition of plasmin. Further studies re-evaluating the drug safety of tranexamic acid and EACA using the recommended and approved doses are necessary.

Estimating the risk of complications related to re-exploration for bleeding after adult cardiac surgery: a systematic review and meta-analysis

“…The risk of significant bleeding is particularly increased by the currently widespread preoperative exposure to potent anti-platelet drugs [1], and likely it will further increase in view of the concerns regarding safety of antifibrinolytics [2]. In this scenario, re-exploration after cardiac surgery is the most feared bleeding-related complication, as it is associated with significant mortality and morbidity [3,4].…”

Safety and Effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial

“…These results were encouraging but left unanswered the question of whether the postoperative dose, coinciding with greatest fibrinolytic activation, was determinant in decreasing postoperative IR and bleeding. Nevertheless newer data indicate that, in a dose-dependent fashion, TA is associated with an increase of adverse events, particularly the observation of seizures [7]. The incidence of this adverse effect varies from 2.7% to 4.6% in any major surgical procedure, independently of dosing schedule [8-10].…”

Early Postoperative Outcomes and Blood Product Utilization in Adult Cardiac Surgery

“…Moreover, the present study addressed potential confounding factors such as pre-operative medication profiles, patient status and intraoperative variables- all of which have been shown previously to independently influence early post-operative outcomes, particularly in the context of evaluating the effects of antifibrinolytics. 5,10,12–19 …”

“…11 However, there were a number of potential confounding issues in these past studies which included but were not limited to patient selection bias, use of off-pump procedures versus CPB, variability in the empirical dosing strategy of aprotinin, and pre-operative medication profiles which can make the interpretation on outcomes difficult. While a continued subject of debate, 12–19 the concerns regarding potential adverse events led to the voluntary withdrawal and discontinuation of aprotinin in November, 2007, with the exception of its availability for compassionate use. As a result, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA), which are generically termed lysine analogues, have now become the most common pharmacological treatment option for antifibrinolytic therapy following cardiac surgery, particularly in patients requiring CPB.…”

“…As a result, tranexamic acid (TXA) and epsilon aminocaproic acid (EACA), which are generically termed lysine analogues, have now become the most common pharmacological treatment option for antifibrinolytic therapy following cardiac surgery, particularly in patients requiring CPB. 3,11–19 Unlike aprotinin, lysine analogues have not been approved as a pharmacological approach to address post-cardiac surgery related bleeding. Furthermore, it remains unknown whether and to what degree adverse events and blood product utilization have been significantly affected with the exclusive use of these lysine analogues when compared to the “aprotinin era” when potential confounding variables are taken into consideration.…”