A 10-year retrospective review of the effectiveness and safety of tranexamic acid in women with inherited bleeding disorders in the peripartum setting

Abstract

Abstract Background: PPH occurs at a rate of nearly 11% globally and is a major cause of maternal mortality worldwide (Carroli, 2008.) Women with inherited bleeding disorders such as hemophilia carriers and those with von Willebrand disease (VWD) are at a substantially greater risk of postpartum hemorrhage (PPH) (Abdul-Kadir, 2014.) TXA use for treatment of PPH has been shown to reduce major bleeding risk without increasing the risk of thromboembolism in patients (Li, 2017). However, the effects of its prophylactic use in patients with bleeding disorders has not been extensively described. The aim of this study was to investigate the effectiveness and safety of prophylactic TXA use in peripartum patients with inherited bleeding disorders. Methods: A retrospective chart review was conducted for all patients with an inherited bleeding disorder cared for by the Multidisciplinary Clinic for Women with Bleeding Disorders (MCWBD) at St. Michael's Hospital (SMH) between 2014 and 2024. We performed descriptive statistical analysis to summarize findings related to bleeding and thrombotic events in patients treated with TXA in the puerperium. Results: There were 296 total patients managed over the course of pregnancy to labour and delivery in the MCWBD over this 10 year time period. 205 had an inherited bleeding disorder (the remainder had an acquired disorder and were not included in the analysis). The median age of patients was 32 (range 18-42). 32% had von Willebrand's Disease, 17% platelet function disorder, 1% hemophilia A,10% symptomatic hemophilia A or B carrier, 18% Bleeding Disorder of Undetermined Cause and 14% rare single clotting factor deficiency. 61% of patients had vaginal delivery, 39% had a C-section. We had access to complete labour and delivery records for 144 patients to allow for reporting of bleeding events. 95% of patients received TXA at some point during delivery. 68% patients received TXA during and after delivery, 11% received TXA only during delivery and 16% received TXA only after delivery. 31% patients also received an additional hemostatic agent (17% received DDAVP, 15% received factor concentrate -VWF:FVIII, FXI, FVIII, rFVIIa and FIX). 17% of patients experienced postpartum hemorrhage (PPH) and of those 88% had primary PPH. 12% of patients with PPH did not use any TXA prophylactically. Two patients who received TXA experienced a thrombotic event post-partum (2/205, 0.98%). One patient with severe factor VII deficiency developed pulmonary embolism 14 days after delivery during which she was being treated with a tapering regimen of rFVIIa and TXA. She had 3 risk factors for VTE: morbid obesity, varicose veins and heterozygosity for factor V leiden mutation. The other patient developed a superficial venous thrombus 1 day after delivery, she had 2 risk factors for VTE: morbid obesity and varicose veins. Conclusions: This data suggests that TXA is associated with very low risk of thrombosis when used as prophylactic treatment for PPH among patients with inherited bleeding disorders in the puerperium. Under 1% of patients over 10 years experienced a thrombotic event and had two or more risk factors for VTE. In contrast, at least 17% had PPH despite provision of preventative peripartum hemostatic therapy that almost always included TXA. This suggests that on balance, TXA should be provided to patients with inherited bleeding disorders with the goal of PPH prevention but caution should be used in those with 2 or more risk factors for thrombosis. Prospective studies on the use of prophylactic TXA in this setting is warranted.