Many drugs have been tested in adults but not in children. Tranexamic acid (TXA) is used to manage excess bleeding. During cardiac surgery cardiopulmonary bypass activates intravascular thrombolysis. This is why antifibrinolytic agents such as transexamic acid can help achieve hemostasis.
Several aspects of neonatal physiology suggest that the dosing requirements for tranexamic acid in neonates might be different than it is for adults. Plasminogen and α2 antiplasmin are decreased while tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor are increased.. Also, due to structural differences in neonatal plasminogen, it is less sensitive to activation by tPA, and activated plasmin is less inhibited by α2 antiplasmin.
Dr. Branden E. Yee and colleagues from the Departments of Anesthesiology and Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, New York, used cord blood samples collected immediately after elective cesarean deliveries of 20 full-term singleton live births to determine the minimum concentration of TXA needed to inhibit fibrinolysis. Their findings appear in this month’s Anesthesia & Analgesia in the article “The Effective Concentration of Tranexamic Acid for Inhibition of Fibrinolysis in Neonatal Plasma In Vitro.” Fibrinolysis was measured using thromboelastography. They compared their results to pooled blood from normal adult plasma.
The authors found that 1000 U/mL tPA produced rapid complete lysis. Concentration-dependent inhibition of fibrinolysis by TXA was also shown with an estimated minimum completely effective concentration of 6.54 μg/mL for neonatal plasma, significantly less than the 17.50 μg/mL concentration seen with adult plasma. The neonatal concentration/effect curve for TXA was significantly different from the adult curve with neonates requiring less TXA compared to adults for the inhibition of fibrinolysis.
This was an in vitro, not in vivo, study, though the basis for adult dosing is the same as was used in this study. Blood drawn from cord/placenta units might be different than blood drawn directly from neonates. Infants with congenital heart disease might also have coagulation abnormalities. The amount of tPA used to initiate fibrinolysis was much larger than is normally used for patients undergoing cardiopulmonary bypass surgery.
As Dr. David Faraoni, Department of Anesthesiology, Queen Fabiola Children’s University Hospital, Free University of Brussels, Brussels, Belgium, and Dr. Susan M. Goobie, Department of Anesthesia, Perioperative and Pain Medicine, Boston Children’s University Hospital, Boston, Massachusetts, state in the accompanying editorial also published in the current edition of Anesthesia & Analgesia, “New Insights About the Use of Tranexamic Acid in Children Undergoing Cardiac Surgery: From Pharmacokinetics to Pharmacodynamics,” this work “is a small yet significant piece of the puzzle that will lead a better use of TXA in children undergoing cardiac surgery. Further studies are still required to assess the PK profile in different age groups having different surgeries and to better define the optimum therapeutic plasma concentration of TXA needed to safely inhibit fibrinolysis in the perioperative period.”