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.