INTRODUCTION:
Antifibrinolytics (AF) reduce bleeding and need for blood product
transfusion in complex cardiac surgery and cardio-pulmonary bypass (CPB)
cases1,2. The two most common AFs are Tranexamic acid
(TXA) and Aminocaproic acid (ACA); both are lysine analogues that
competitively inhibit conversion of plasminogen to
plasmin3-5. AFs have demonstrated robust blood-loss
reducing effects in a variety of settings without increased risk of
thromboembolic events6. In 2011, The Society of
Cardiovascular Anesthesiologists and Society of Thoracic Surgeons gave
TXA their highest recommendation for use in blood conservation
strategies although ACA is comparable in both efficacy and side effect
profiles7. In the recent decade, use of AFs has
expanded in both cardiac and non-cardiac surgery, with clinical
applications in a wide range of surgical specialties8.
The landmark CRASH-2 study concluded that early TXA reduced mortality in
trauma patients9. Shortly thereafter, the MATTERs
study reported similar benefits in the US military10.
These compelling results led to an almost overnight paradigm shift and
near worldwide incorporation of AF in trauma center resuscitation
protocols, but questions soon followed. Why did less than half of the
patients in CRASH-2 require PRBCs if they were bleeding to
death?11 Why did only 5% of CRASH-2 patients die from
hemorrhage11? CRASH-2 was also conducted in areas with
underdeveloped rural trauma systems, leading to questions regarding
application of CRASH-2 findings to mature urban trauma
systems12, 13. Although TXA and ACA are generally
well-tolerated, deleterious effects include increased risk of seizure
and increased mortality in certain high-risk
subpopulations14, 15. Concern over these findings and
persistent questions about the mechanism of action have resulted in
variable integration of AFs in US trauma centers16-18.
Coagulopathy in cardiac and trauma surgery is diagnosed via a
combination of conventional coagulation tests and viscoelastic assays
such as the Thromboelastogram (TEG). TEG provides point-of-care
evaluation of coagulation abnormalities and can guide coagulopathy
treatment and decrease blood product use in cardiac
surgery19-21.
The TEG LY30 value has been used to stratify distinct fibrinolytic
phenotypes among trauma patients. The physiologic phenotype is defined
as LY30=0.8-3.0% and is associated with the lowest
mortality22. However, if TXA was administered to
trauma patients who present to the hospital with physiologic levels of
fibrinolysis, they had the highest mortality23. At the
very least, this suggests that some patients may benefit from TXA more
than others and that the mechanism may be associated with
fibrinolysis24-28.
While there is some evidence regarding distribution and functional
consequences of fibrinolytic phenotypes in trauma patients, no studies
to date have investigated these ideas in cardiac surgery patients. The
aim of this study was to fill that gap.