Use of Low Dose Tranexamic Acid in Patients with Bleeding Disorders

Tranexamic acid (TXA) is an antifibrinolytic drug that inhibits fibrinolysis by displacing plasminogen from fibrin. It is widely used to prevent bleeding in patients with trauma, heavy menstrual bleeding, postpartum hemorrhage, and procedures/surgeries in patients with bleeding disorders. However, a paucity of robust dose exposure and pharmacokinetic studies have led to varied dosing regimens across different trials.

Oral TXA is used for heavy menstrual bleeding (HMB) and minor surgeries/procedures involving mucosal surfaces in patients with bleeding disorders. It is available as 650 mg tablets in the United States and 500 mg tablets outside the US. The recommended dose for post adolescent individuals with HMB is 1300 mg three times a day. While the World Federation of Hemophilia (WFH) guidelines recommend TXA for procedures/surgeries in hemophilia, no optimal dosing regimen is recommended. Most hematologists use 1300 mg (or 1 to 1.5 g) three times a day for adults and 20-25 mg/kg/dose for children. (Van Galen 2019; Relke 2021). Recent work (Li Shuhi 2021) demonstrated that lower doses of 500 and 650 mg achieved the same therapeutic target as 1000 mg doses to prevent PPH. We describe our experience with the use of low dose oral TXA (650 mg) for patients with bleeding disorders.

This retrospective, single-center study, approved by the Institutional Review Board (IRB), analyzed medical records over a 4-year period to evaluate the efficacy of low-dose oral TXA in patients with bleeding disorders. A total of 404 patients received 1013 prescriptions for oral TXA. The median age of the cohort was 28 years with 321 adults (79%) and 85 pediatric (21%) patients. 88 patients (21.6%) were overweight while 100 patients (24.6%) were obese. A wide range of bleeding disorders were represented in the cohort: 125 (30.9%) with Hemophilia A; 31 (7.6%) with Hemophilia B; 26 (6.4%) Hemophilia A/B carriers; 146 (36.1%) with Von Willebrand disease; 26 (6.4%) with Factor XI deficiency; 12 (2.9%) with platelet dysfunction; 6 (1.5%) with fibrinogen disorders and 33 (8.2%) with other rare bleeding disorders.

All 404 patients were prescribed 650 mg three times a day for 5-7 days. The major indications for oral TXA were HMB, epistaxis, mouth bleeding and minor procedures/surgeries. 179 procedures were successfully performed using 650 mg three times a day for 5-7 days with or without other therapies and only 1 patient needed an increase in the dose to 1300 mg due to excessive bleeding. These procedures included 62 (34.6%) surgeries, 42 (23.4%) minor procedures and 71 (40%) dental extractions

The same low dose was used in 67 patients with HMB. 40 (59.7%) patients had resolution of HMB on TXA monotherapy and 27 women needed to add or switch to hormonal therapies. 3 out of 40 (7.5%) women on TXA monotherapy needed an increase in the dose to 1300 mg. No adverse effects were observed.

Additionally, the use of TXA in rare bleeding disorders is not well studied. We report the use of TXA for HMB and/or perioperative management in 77 patients with rare bleeding disorders (other than Hemophilia or Von Willebrand disease).

This study demonstrates that low dose oral TXA at 650 mg three times a day is safe and effective to prevent HMB and bleeding from minor procedures/surgeries in patients with bleeding disorders.