Tranexamic Acid Use in the Postpartum Period Since the WOMAN Trial: A Retrospective Chart Review.

OBJECTIVE: To analyze the use of tranexamic acid (TXA) in postpartum patients since the World Maternal Antifibrinolytic (WOMAN) trial. METHODS: A retrospective chart review was conducted from May 2017 to March 2020 at a tertiary care centre to identify all patients who received TXA for postpartum bleeding. The primary outcome was to identify the proportion of patients who received TXA as per World Health Organization guidelines created using results of the World Maternal Antifibrinolytic trial. RESULTS: A total of 231 patients were included in our analysis. Use increased over time with 18 patients in 2017, 51 in 2018, and 134 in 2019 receiving TXA. In all, 203 patients (87.9%) received TXA within recommended guidelines, and these patients were less likely to require surgery or interventional radiology (12.3% vs. 42.9%, P < 0.001) or blood transfusion (23.6% vs. 42.9%, P = 0.030), and they had a lower likelihood of overall adverse outcomes (1.62 (1.6) vs. 2.60 (2.0), P = 0.024). TXA was commonly used as the first-line agent for postpartum bleeding (48.9% of patients), more likely administered at cesarean section (77.0%) and when estimated blood loss did not meet criteria for "true" postpartum hemorrhage (41.6% of patients). Use of TXA as the first medication was associated with fewer overall adverse outcomes than misoprostol (P = 0.035). A shorter time to administration of the first medication was associated with shorter postpartum admission time (P = 0.042). CONCLUSIONS: The majority of patients received TXA within guidelines and experienced fewer adverse outcomes. Further study is needed to identify the best order of TXA administration with additional uterotonics and whether TXA should be used prophylactically in some groups for postpartum bleeding.

p14ARF inhibits the growth of p53 deficient cells in a cell-specific manner.

While p14(ARF) suppression of tumorigenesis in a p53-dependent manner is well studied, the mechanism by which p14(ARF) inhibits tumorigenesis independently of p53 remains elusive. A variety of factors have been reported to play a role in this latter process. We report here that p14(ARF) displays different effects on the anchorage-dependent and -independent growth of p53-null/Mdm2 wild type cells. p14(ARF) blocks both the anchorage-dependent and-independent (soft agar) proliferation of 293T and p53(-/-) HCT116, but not p53-null H1299 lung carcinoma cells. While p14(ARF) had no effect on the anchorage-dependent proliferation of p53(-/-) MEFs and Ras12V-transformed p53(-/-) MEFs, it inhibited the growth of Ras12V-transformed p53(-/-) MEFs in soft agar. Furthermore, ectopic expression of p14(ARF) did not lead to degradation of the E2F1 protein and did not result in the reduction of E2F1 activity detected by two E2F1 responsible promoters, Apaf1 and p14(ARF) promoter, in 293T, p53(-/-) HCT116, and H1299 cells. This is consistent with our observations that p14(ARF) did not result in G1 arrest, but induced apoptosis via Bax up-regulation. Taken together, our data demonstrate that the response of p53-null cells to ARF is cell type dependent and involves factors other than Mdm2 and E2F1.