Abstract 521: A Pilot Study Comparing Anti-Inflammatory Effects of Tranexamic Acid and Epsilon Aminocaproic Acid in Pediatric Congenital Heart Surgery

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Nirbhay Parashar ◽  
Tarek Nafee ◽  
Cheryl Lefaiver ◽  
Christine Steffensen ◽  
Vince Rizzo ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Pilot Study ◽  
Tranexamic Acid ◽  
Heart Surgery ◽  
Pediatric Patients ◽  
Aminocaproic Acid ◽  
Antifibrinolytic Agents ◽  
Gm Csf ◽  
Anti Inflammatory ◽  
Epsilon Aminocaproic Acid

Background: Antifibrinolytic agents are frequently used during pediatric heart surgery with cardiopulmonary bypass (CPB) to reduce transfusions. There are no studies comparing anti-inflammatory effects of antifibrinolytic agents, tranexamic acid (TXA) and Epsilon Aminocaproic acid (EACA). We compared the two agents in pediatric patients undergoing redo sternotomy with CPB. Aim: To compare anti-inflammatory effects of tranexamic acid versus aminocaproic acid in pediatric patients undergoing redo sternotomy and cardiopulmonary bypass. Methods: We conducted a randomized, double blind pilot study, comparing 10 subjects in each group receiving EACA and TXA. A cytokine panel was used to measure 13 inflammatory markers in pre, immediate post and 24 hours post-CPB period. Between group comparisons were tested with Mann-Whitney U tests and within group comparisons with Friedman tests. Results: Sample characteristics were comparable in both groups. Post CPB, plasma levels of 7 markers increased significantly (p<0.05) in both groups, including MCP-1; 3 increased significantly (p<0.03) in the EACA group alone, including GM-CSF; and 3 did not change over time (Table 1). No difference was found between groups for markers except for IL-10, which was significantly higher in EACA group post CPB. While absolute values of markers, chest tube output and volume of blood product needs were lower in TXA group, the differences were not statistically significant. Conclusion: There was no significant difference in anti-inflammatory profiles between EACA and TXA in this pilot study. GM-CSF and MCP-1 were increased in our study post CBP which has not been described in previous studies.

scholarly journals Comparison of intraoperative tranexamic acid and epsilon-aminocaproic acid in cardiopulmonary bypass patients

JTCVS Open ◽  
2020 ◽  
Vol 3 ◽  
pp. 114-125
Author(s):  
Mark Broadwin ◽  
Patrick E. Grant ◽  
Michael P. Robich ◽  
Monica L. Palmeri ◽  
Frances L. Lucas ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Tranexamic Acid ◽  
Aminocaproic Acid ◽  
Epsilon Aminocaproic Acid

Procoagulant Activity of Antifibrinolytic Agents; A Novel Hemostatic Mechanism of Tranexamic Acid and Epsilon-Aminocaproic Acid.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1151-1151
Author(s):  
Kenichi Ogiwara ◽  
Keiji Nogami ◽  
Katsumi Nishiya ◽  
Nobuyuki Tsujii ◽  
Midori Shima
Keyword(s):  
Tranexamic Acid ◽  
Research Funding ◽  
Thrombin Generation ◽  
Aminocaproic Acid ◽  
Coagulation Factors ◽  
Hydrolytic Activity ◽  
Procoagulant Activity ◽  
Clinical Effects ◽  
Antifibrinolytic Agents ◽  
Epsilon Aminocaproic Acid

Abstract Abstract 1151 Tranexamic acid (TA) and epsilon-aminocaproic acid (EACA) of lysine analogs have been clinically used as antifibrinolytic agents. These hemostatic mechanism is that TA/EACA bind to lysine-binding sites (LBS) of plasmin (Plm)/plasminogen (Plg) and competitively prevents Plm/Plg from binding to fibrin(ogen), resulting in inhibition of Plm-induced fibrin(ogen) degradation. TA/EACA cause a conformational change of (Glu-)Plg by LBS binding, however, resulting in paradoxical promotion of Plg activation by Plg activators (PA). It has been known in vitro that TA/EACA promote Plm generation simultaneously with inhibiting fibrinolysis, but clinical effects are poor understood. We have recently demonstrated that Plm possessed the procoagulant activity by catalytic proteolysis of factor (F)VIII, FV as well as FXII. In this study, we examined whether TA/EACA affected on the coagulation system through elevation of PA-induced Plm generation. In rotation thromboelastometry (ROTEM), the addition of urokinase (uPA, 80 IU/ml) to whole blood diminished the maximum clot firmness, indicative of hyperfibrinolysis. Furthermore, chromogenic assay for Plm-hydrolytic activity and calibrated automated thrombography (CAT) revealed that the addition of uPA elevated Plm activity and peak level of thrombin generation, respectively, in normal plasma. These findings supported that uPA promoted Plm generation, resulting in enhancement of fibrinolysis and procoagulant activity. Various concentrations of TA/EACA were added into whole blood or plasma prior to reactions with uPA (Fig.1). Fibrinolytic effects of uPA obtained in ROTEM were inhibited by TA/EACA dose-dependently (IC50; TA/EACA ∼0.5 micro M/∼1.5 micro M), similar to previous reports. However, uPA (20 IU/ml) -induced Plm activity obtained in Plm-hydrolytic activity increased in the presence of TA/EACA by ∼6-fold (EC50; TA/EACA ∼0.2 mM/∼1.5 mM), followed by decreasing at higher concentrations. Interestingly, the effect of TA/EACA on uPA-induced procoagulant activity observed as elevation of peak thrombin in CAT was biphasic pattern, similar to that on Plm activity in Plm-hydrolytic activity, i.e. peak thrombin was elevated by ∼2-fold by TA/EACA (EC50; TA/EACA ∼0.3 mM/∼1.5 mM), and after reaching maximum (TA/EACA ∼1 mM/∼10 mM), it decreased. Effects of TA/EACA on Plm generation and thrombin generation were both diminished by aprotinin, a potent Plm inhibitor, indicating that the procoagulant effect interacted closely with Plm generation. Since α2-antiplasmin (AP) neutralizes Plm in plasma, excess of Plm unlikely exerts the procoagulant activity. Since AP binds to Plm via LBS, however, TA/EACA prevents AP from binding to Plm. We confirmed that TA/EACA protected Plm from AP binding (IC50; TA/EACA ∼1 mM/∼10 mM) in purified systems. Furthermore, in the presence of uPA in plasma, FV and FVIII activities were immediately elevated, followed by slow decrease. FVII activity increased gradually by ∼1.5-fold. TA/EACA did not inhibit the effects of uPA on the coagulation factors, but rather accelerated. Taken together, we demonstrated a novel hemostatic mechanism that TA/EACA exerted the procoagulant activity by LBS binding of Plg/Plm; i.e. 1) promoting uPA-induced Plm generation, 2) inhibiting Plm binding to fibrin(ogen) (increasing free Plm), 3) inhibiting neutralization of free Plm by AP, 4) conserving Plm action to several coagulation factors (FV, FVII, FVIII). This mechanism might provide a clarification of clinical effects of TA/EACA including why some severe hemophilia A patients were successfully treated with EACA alone (Ghosh et al. Haemophilia. 2004;10:58). Disclosures: Ogiwara: Baxter Hemophilia Scientific Research and Education Fund in Japan 2009: Research Funding. Nogami:Bayer hemophilia award program 2009: Research Funding.

Tranexamic Acid Reduces Bleeding After Cardiopulmonary Bypass When Compared to Epsilon Aminocaproic Acid and Placebo

1997 ◽  
Vol 12 (5) ◽  
pp. 330-338 ◽  
Author(s):  
Mark L. Pinosky ◽  
Dan J. Kennedy ◽  
Richard L. Fishman ◽  
Scott T. Reeves ◽  
Calvert C. Alpert ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Tranexamic Acid ◽  
Aminocaproic Acid ◽  
Epsilon Aminocaproic Acid

Prophylactic use of low dosages of tranexamic acid and epsilon aminocaproic acid in heart surgery

2010 ◽  
Vol 27 ◽  
pp. 102
Author(s):  
Rodríguez E. Casas ◽  
Rodríguez F. Salgueiro ◽  
Machado M. Valdés ◽  
Morlans K. Hernández ◽  
Sainz H. Cabrera
Keyword(s):  
Tranexamic Acid ◽  
Heart Surgery ◽  
Aminocaproic Acid ◽  
Prophylactic Use ◽  
Epsilon Aminocaproic Acid

epsilon-Aminocaproic Acid Plasma Levels During Cardiopulmonary Bypass

1997 ◽  
Vol 85 (2) ◽  
pp. 248-251
Author(s):  
Elliott Bennett-Guerrero ◽  
Jonathan G. Sorohan ◽  
Andrew T. Canada ◽  
Liza Ayuso ◽  
Mark F. Newman ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Plasma Levels ◽  
Aminocaproic Acid ◽  
Epsilon Aminocaproic Acid

Comparison of epsilon aminocaproic acid and tranexamic acid in pediatric cardiac surgery

2004 ◽  
Vol 18 (2) ◽  
pp. 141-143 ◽  
Author(s):  
Sandeep Chauhan ◽  
Sambhu N Das ◽  
Akshay Bisoi ◽  
Shailaja Kale ◽  
Usha Kiran
Keyword(s):  
Cardiac Surgery ◽  
Tranexamic Acid ◽  
Aminocaproic Acid ◽  
Pediatric Cardiac Surgery ◽  
Epsilon Aminocaproic Acid

Hemorrhagic Complications With Adenotonsillectomy In Children and Young Adults With Bleeding Disorders

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3611-3611
Author(s):  
Deepti M. Warad ◽  
Fareeda TN. Hussain ◽  
Shelagh A. Cofer ◽  
Vilmarie Rodriguez
Keyword(s):  
Young Adults ◽  
Tranexamic Acid ◽  
Surgical Procedures ◽  
Pediatric Patients ◽  
Aminocaproic Acid ◽  
Bleeding Complications ◽  
Recurrent Bleeding ◽  
Bleeding Disorders ◽  
Hemorrhagic Complications ◽  
Children And Young Adults

Abstract Hemorrhagic complications remain a challenge with surgical procedures in patients with bleeding disorders. Tonsillectomy and adenoidectomy are some of the most common surgical procedures performed in pediatric patients. Adequate hemostasis in patients with bleeding disorders is centered on comprehensive hemostatic support and dexterous surgical technique. To assess our institutional experience with children and young adults with bleeding disorders that underwent tonsillectomy and/or adenoidectomy we performed a retrospective chart review of all such patients (age< 25 years) over duration of 20 years from July 1992 to July 2012. Nineteen patients were identified. The mean age was 10.2 years (Range 2.5 – 23.2 years) with 13 females and 6 males. The cohort included 2 patients with platelet disorders, 5 patients with von Willebrand disease and 12 patients with factor deficiencies (see table 1). Sixteen patients (84%) underwent tonsillectomy and adenoidectomy, while 3 patients (16%) underwent tonsillectomy only. Pre-operative treatment in the form of coagulation factor infusion (with a goal of 100% factor levels prior to surgery) or DDAVP was given to 16 patients (84%). Nine patients (47%) received anti-fibrinolytic agent, aminocaproic acid, starting pre-operatively for an average of 15.5 days (Range 10 – 36 days) post-operatively. Six patients (32%) received aminocaproic acid only post-operatively for an average of 12 days (Range 7-14 days). One patient received Tranexamic acid for 19 days. Intraoperative hemostasis was achieved by electrocautery in 16 patients (84%) and coblation technique in 2 patients (10%). Surgical hemostasis technique for 1 patient was undocumented, however this patient did not have any bleeding complications subsequently. Ten patients (53%) experienced post-operative hemorrhage including 2 patients (10%) with early (<24 hours) bleeding and 8 patients (42%) with delayed (>24 hours) bleeding from surgical site. Bleeding resolved spontaneously in 2 patients while 8 patients (42%) required interventions such as cauterization (4 patients), extended aminocaproic acid dosing (4 patients), DDAVP (1 patient), DDAVP and tranexamic acid (1 patient), recombinant factor VII (1 patient), Humate-P® (1 patient), Factor VIII infusion (1 patient) and Factor IX infusion (1 patient). Three patients (30% of bleeding patients) required transfusions including 1 patient that received platelet transfusions, 1 patient received PRBCs and another patient received FFP. Recurrent bleeding was noted in 3 patients and the rate was significantly higher in older patients amongst those with bleeding complications (p=0.0189).Table 1Age (years, months)GenderDiagnosisSeverity of diseasePost-operative bleeding (Early ≤ 24 hours, Delayed >24 hours)Recurrent bleeding14,5MEssential ThrombocythemiaModerateEarlyYes13,6MFactor VII deficiencyMildDelayedNo6,7FFactor VII deficiencyMildDelayedNo7,6FFactor VII deficiencyMildNo-11,2FFactor XI deficiencyMildEarlyNo8,4MHemophilia ASevereDelayedNo9,4FHemophilia A carrierMildDelayedNo15,2FHemophilia A carrierMildNo-5,0MHemophilia BMildNo-23,2MHemophilia BMildDelayedYes6,1FHemophilia B carrierMildNo-6,8FHemophilia B carrierMildNo-15,2FHemophilia B carrierMildNo-11,4FMay-Hegglin anomalyModerateDelayedNo4,0FType 1 von WillebrandMildDelayedNo13,5FType 2A von WillebrandModerateDelayedYes2,5MType 2A von WillebrandModerateNo-9,9FType 2B von WillebrandModerateNo9,1FType III von WillebrandSevereNo- The rate of bleeding complications in pediatric patients with mild bleeding disorders undergoing adenotonsillectomy has been reported to be similar to that of normal population. In our cohort, delayed bleeding was more common than early bleeding consistent with current literature. We observed a higher rate of bleeding complications (53%) than reported in literature despite aggressive hemostatic support and adequate surgical techniques; however, our sample size was limited. Although there was no association between delayed hemorrhage and age, recurrent bleeding was associated with older age. We conclude that patients with bleeding disorders undergoing adenotonsillectomy are at a higher risk of bleeding and require close monitoring with hemostatic support for a prolonged period of time in post-operative period. Disclosures: No relevant conflicts of interest to declare.

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