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.