Antithrombotic therapy in cardiac surgery

Abstract

Purpose: To review the perioperative management of antithrombotic therapy in cardiac surgery, including the management of cardiopulmonary bypass (CPB) and off-pump surgery.Methods: A review of the relevant English literature over the period was undertaken, in addition to a review of international practices in antithrombotic therapy in cardiac surgery. Principal findings:Cardiopulmonary bypass is required in most procedures and makes anticoagulation mandatory. Anticoagulation is, usually, achieved with unfractionnated heparin (UFH). Unfractionated heparin is monitored by point-ofcare (POC) testing, such as the activated clotting time or the determination of heparin concentration. The target values of both tests remain empirical, with no clearly validated thresholds. The target value needs to be adjusted according to the POC test, given significant variations between devices and activators. After CABG, the need for antiplatelet therapy is well demonstrated, in order to limit the risk of postoperative death or ischemic events, and improve venous graft patency. Immediately after valvular surgery, antithrombotic therapy should take into account the specific risk carried by each patient and by each prosthetic device. The risk of venous thromboembolism, though poorly defined, is also present in the postoperative period and may require additional attention. Given the frequent exposure to UFH, occurrence of heparininduced thrombocytopenia is not infrequent in these patients and requires careful individual management. Conclusions:Antithrombotic therapy is an essential component of cardiac surgery. Yet, with the exception of antiplatelet agents in CABG patients, antithrombotic therapy is often based on the clinical experience of medical teams more than on an evidence-based assessment of the literature. Objectif Constatations principales : La circulation extracorporelle est nécessaire pour la majorité des opérations et rend l'anticoagulation obligatoire. L'anticoagulation est, habituellement, réalisée avec de l'héparine non fractionnée (HNF). L'HNF est contrôlée par des tests faits au chevet du malade comme le temps de coagulation activée ou la détermination de la concentration d'héparine. Les valeurs cible des deux tests demeurent empiriques, sans valeurs seuil clairement validées. La valeur cible doit être ajustée en fonction de chaque test de chevet à cause des variations significatives entre les instruments et les activateurs. Après le pontage aortocoronarien (PAC), la nécessité d'un traitement antiplaquettaire a été bien démontrée, qui vise à limiter les décès postopératoires ou les incidents ischémiques et à améliorer la

Anticoagulant therapy during cardiopulmonary bypass

“…Long chains accelerate the inhibition of thrombin (anti-IIa activity), while smaller fragments inhibit factor Xa (anti-Xa activity). UFH has an anti-IIa/anti-Xa ratio of 1:1 [14]. Maintenance of high heparin levels during CPB has been reported to be associated with reduced contact activation; decreased consumption of coagulant proteins, and a reduced inflammatory response [18].…”

“…The antithrombin III-dependency of UFH is, at least in part, responsible for its variable pharmacodynamics. In addition, depletion of antithrombin III during CPB impacts anticoagulant response, and may also influence clinical outcome among patients undergoing cardiac surgery [1,14,19,20]. UFH binds non-specifically to endothelial cells (with subsequent endocytosis), plasma proteins (thereby limiting the amount of heparin available to complex with antithrombin III), macrophages within the reticuloendothelial system (facilitating drug clearance), and platelet factor 4 (an initiating event for heparin-induced thrombocytopenia [HIT]) [17].…”

“…Unfractionated heparin (UFH), administered to maintain a state of anticoagulation and attenuate the highly prothrombotic environment of CPB, and post-bypass neutralization with protamine sulfate are mainstays of therapy worldwide, and despite clear limitations have been difficult to replace in contemporary practice [13][14][15].…”

Preservation of Haemostasis with Anti-thrombotic Serotonin Antagonism

“…All the early work with these compounds involved experimental surgery on animals, and it was of note that, unlike similar experiments with other anti-thrombotic drugs, there was no excess bleeding, and no oozing coagulopathy. This makes these drugs particularly attractive to surgeons wanting to protect their patients from arterial thrombosis in the peri-operative period [40]. So, is it possible that, contrary to received opinion, the anti-thrombotic activity of 5HT 2A antagonists can be accompanied by an absence of effect on haemostasis.…”

First in man study of EP217609, a new long-acting, neutralisable parenteral antithrombotic with a dual mechanism of action

“…Heparin with its antidote protamine is the current standard of care, but its use is empiric, i.e. not based on adequate randomised clinical trials, and associated with limitations and side effects [7][8][9]. EP217609 and its antidote avidin have entered clinical development and may ultimately provide an alternative to heparin and protamine.…”