4. Discussion:
Bleeding is the main concern when operating on patients on
anticoagulants with possibly requiring blood transfusion and
re-exploration, both identified as independent risk factors for
postoperative morbidity and mortality.1,2,5,6 In a
study of over 18,000 patients at 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%).5 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 one 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.8
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.9 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.42 Likewise, in a meta-analysis of
557,923 patients, 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.6
The risk of bleeding complications in emergency settings in patients on
anticoagulants has not been studied in large patient
cohorts.40 Nevertheless, 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 1-year post
surgery.7 Similarly, Kapetanakis showed a higher rate
of blood transfusions and re-exploration in patients who received
clopidogrel prior to urgent CABG.43 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.44
Cardiac surgery, compared to other surgical specialties, presents a
unique challenge. 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
CPB. Therefore, it is paramount that any treatment modalities instituted
preoperatively in an attempt to correct the coagulopathy do not
interfere with the ability to fully and rapidly anticoagulate with
heparin in preparation for CPB. It is also important to avoid the
potential of a hypercoagulable state that may increase the
thromboembolic risk and overall morbidity.45
The decision process is easier in patient where surgery can be done
semi-electively or at least delayed for adequate anticoagulant washout,
as per the guidelines set forth by the STS.46 Patients
with high risk for thromboembolism can be bridged on short half-life
medications such as heparin that surgeons are most comfortable dealing
with and can be quickly reversed. Patients on anticoagulants presenting
with an ACS may persuade surgeons to push for alternatives to surgical
intervention such as PCI rather than dealing with a bleeding patient,
even if the patient’s anatomy and long-term outcome favor surgical
revascularization.
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.47 Other examples include
endocarditis and sepsis, where underlying issues such as DIC, dilution
and hemolytic anemia worsens coagulopathy. In addition, CPB creates its
own insults of endothelial activation, fibrinolysis, coagulopathy and
consumption of platelets and coagulation factors, all aggravating an
already attenuated hematological profile.48
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 from controlled trials. Proper knowledge
of mechanism of action of the anticoagulants on coagulation cascade and
the effectiveness of available antidotes 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 practice
ensures appropriate and judicious use of these reversal agents.