4. Discussion:
The deleterious effects of blood transfusions are well documented and calls have been made to restrict their use. In a study of greater than 18,000 patients at The Cleveland Clinic over 10-years, it was noted that transfusions and reoperations for bleeding were independently associated with increased risk of morbidity and mortality (8.5% vs 1.8%).2 Similarly, others showed a higher mortality (14.2% vs 3.4%) in patients requiring re-exploration compared to the rest, and the amount of packed red blood cells (pRBC) was associated with an incremental increased risk (0.25% for each unit transfused).41 In another study of almost 5,400 patients, those who required re-exploration for bleeding had a twofold mortality increase in early postoperative period, as well as an overall mortality increase beyond 90 days.42 In addition, a meta-analysis review of observational studies showed that preoperative exposure to clopidogrel was associated with increased risk of death, blood loss, transfusions and reoperations.44 An individualized strategy for clopidogrel suspension was suggested in patients undergoing CABG following ACS, guided by platelet function testing, which significantly reduced postoperative bleeding and blood use.45
A review of 528,686 CABG patients, from the Society of Thoracic Surgery (STS) database, revealed that patients requiring emergent surgery or were on antiplatelet medications within 24-hours before the operation had a significantly higher rate of re-exploration for bleeding, with an increased risk-adjusted mortality of 5.9% compared to 2.0% for others.43 Likewise, a meta-analysis of 557,923 patients found emergency surgery and preoperative aspirin use were among the risk factors resulting in higher rate of re-exploration with an increased risk of mortality and major morbidity.1 In a separate study, it was noted that patients who received clopidogrel prior to urgent CABG had a higher rate of re-exploration and blood transfusions.47 Finally, an international prospective study of patients undergoing urgent CABG on antithrombotic agents (ACUITY trial) noted that transfusions of ≥ 4 units pRBC was an independent mortality risk factor for up to one year post surgery.46
The decision process is easier in patients for whom surgery can be done semielectively or at least delayed for adequate anticoagulant washout, as per the guidelines set forth by the STS.48 Patients with high risk for thromboembolism can be bridged on short half-life medications such as heparin that can be quickly reversed. Patients with multi-vessel CAD on anticoagulants presenting with ST-elevation myocardial infarction (STEMI) would undergo PCI of the culprit vessel and surgical revascularization delayed until adequate anticoagulant washout.
However, it is inevitable that surgeons will be confronted where emergency surgery is needed for patients on anticoagulants. Examples would be a patient with ACS where PCI in not possible due to coronary anatomy or lack of expertise, or a patient with an aortic dissection, where the risk of bleeding is further aggravated by coagulopathy induced by hypothermia and circulatory arrest, resulting in platelet dysfunction and reduced activity of clotting factors.49 Other examples include endocarditis and sepsis, where underlying issues, such as dilution, hemolytic anemia and disseminated intravascular coagulopathy (DIC) worsen the coagulopathy. In addition, CPB creates its own insults of endothelial activation, fibrinolysis, and consumption of platelets and coagulation factors, all aggravating an already attenuated hematological profile.50
Several documents and guidelines have been established with regards to treatment of patients on oral anticoagulants presenting with an acute bleed, or in the perioperative setting of emergency surgeries, mainly non-cardiac, where correction of the coagulopathy typically takes place before the incision is made.20,51 Cardiac surgery patients, on the other hand, present a unique challenge, especially in an emergency setting, where answers to some of the following questions may shed some light on the dilemma and aggressiveness in attempting to correct an underlying coagulopathy:
1-Does the preoperative administration of reversal agents hamper subsequent heparinization and achievement of therapeutic ACT needed for CPB? If so, when is the best time to administer, pre or post pump? While a normal coagulation profile is initially desirable to ensure a dry entry and minimize blood loss, the patient will paradoxically require full anticoagulation shortly thereafter for initiation of CPB. Therefore, it is paramount that any treatment modalities instituted to correct the coagulopathy do not interfere with the ability to fully and rapidly anticoagulate with heparin in preparation for CPB. Reports have emerged on the difficulty of adequately anticoagulating patients with heparin required for CPB or even during endovascular repair procedures following the administration of andexanet alfa that has led to heparin resistance.33 This is due to the binding of andexanet alfa to heparin-antithrombin complexes preventing them from exerting their anticoagulant function. Higher doses of heparin or antithrombin supplementation maybe required to achieve therapeutic anticoagulation.31,32
Therefore, pre CPB administration of specific reversal antidotes in a situation of primary sternotomy for emergency CABG, where minimal tissue dissection is anticipated, heparin resistance might be problematic if quick initiation of CPB is needed. On the other hand, redo-sternotomy cases require meticulous tissue dissection and a “dryer” operative field, where pre CPB correction of underlying coagulopathy would be desirable. Surgical judgment will dictate the need of full or partial correction of coagulopathy depending on the anticipated amount of dissection, realizing that heparin resistance may become an issue later on.
2-What is the risk of thromboembolism? Attention is generally directed towards avoiding bleeding, but discussion is not complete without noting the risk of thromboembolism secondary to anticoagulant interruption.8,9 Postoperative bleeding will require longer delay in the resumption of the anticoagulant with the potential of increased postoperative thromboembolic risk. While achieving near normal lab values is desirable, the reversal agents may have the unwanted effect of causing thrombosis, and their impact on improving outcomes is not well established.24,30 However, the thromboembolic rate with PCC treatment was noted to be comparable with that of anticoagulation discontinuation without reversal. While the studies examining the reversal agents were prospective, they were open-labeled and lacked a control group.22,27 The timing of postoperative anticoagulant resumption should be based on the bleeding vs thrombotic risk according to the CHA2DS2-VASc Score.34
3-Is postoperative anticoagulation needed, as in cases with mechanical valves or post pump assist devices? These patients present additional challenges, where aggressive correction of coagulopathy may lead to valve or device circuit thrombosis. The use of heparin-bonded tubing as well as biological rather than mechanical valves should be considered. Surgical judgment and patient’s clinical condition will have to dictate proper course of action. For example, slight increase in chest tube drainage can be tolerated, and aggressive correction of lab values if patients are not bleeding is probably unnecessary and should be avoided.
4-Was the underlying indication for preoperative anticoagulation addressed at the time of surgery? An example would be concomitant MAZE and left atrial appendage (LAA) clipping for preexisting AF (STS Class I recommendation, evidence level A and B), where the risk of future postoperative embolization may be reduced such that the coagulopathy can be corrected and the need for postoperative anticoagulation avoided or at least delayed.52
Proposals in the literature on management of the cardiac surgical patient on anticoagulants in the acute setting are mainly based on expert opinion and extrapolation from non-emergent cardiac or emergent non-cardiac guidelines, rather than from controlled trials. Proper knowledge of mechanism of action of the anticoagulants and the effectiveness as well as potential limitations of available reversal agents is important. These agents are costly and may lead to heparin resistance that could preclude timely institution of CPB; therefore, their judicious use is essential. Decision is typically made on a case-by-case basis considering product availability, local hospital policies and overall patient’s clinical condition. The development of hospital and system-wide strategies that promote a multidisciplinary approach utilizing evidence-based clinical practices ensures appropriate and judicious use of these important resources.