173: Pharmacodynamics of tranexamic acid use for hemorrhage prevention at cesarean delivery

Abstract

To determine the pharmacodynamic profile of tranexamic acid (TXA) given at cesarean delivery using rotational thromboelastometry. We expected that as the drug was cleared metabolically, it would be less likely to reverse the ex vivo effect of tissue plasminogen activator (tPA). We administered 5mg/kg of intravenous tranexamic acid to pregnant women at the time of umbilical cord clamp. Blood samples were collected prior to delivery, after administration within 10 minutes, 30-60 minutes, 1.5-3 hours, 4-6 hours, 7-8 hours and 24 hours. We performed rotational thromboelastometry using EXTEM, APTEM and EXTEM with spiked tPA serially. Inclusion criteria included > 34 weeks gestation, normal renal function and scheduled cesarean delivery. Women were excluded if they had a history of thrombophilia or were on anticoagulation. Our primary outcome was maximum lysis (ML) at 60 minutes in EXTEM samples with tPA over time. We also looked at maximum clot firmness (MCF) prior to and immediately after drug administration. We included 10 women in our study and 9 completed all blood draws. Women were on average 33 ± 4.7 years old, 38 weeks (range 34-39) in gestation and had a body mass index (BMI) of 33.2 ± 7.2 kg/m2. ML values for EXTEM with tPA over time are included (Table). The average ML and standard deviation (SD) are 99.7% (SD 0.5) for pre-delivery and 4.9% (1.8), 14.8% (11.1), 49.9% (35.3), 79.9% (22.7), 86.9% (25.1), 88.3% (31.7) for each corresponding serial blood draw as detailed above. A representative sample of assays over time is included (Figure). MCF for pre-delivery, 73 ± 3.6 mm, and within 10 minutes of drug administration, 70 ± 6.3 mm, was not different (p=0.19). The effects of tranexamic acid given in vivo appears to reverse the added ex vivo tPA until about 7- 8 hours after administration, though there is some variability in drug clearance. There does not appear to be evidence of hypercoagulability by rotational thromboelastometry after TXA administration.View Large Image Figure ViewerDownload Hi-res image Download (PPT)