The Use of Liquid Tranexamic Acid for Pediatric Patients with Bleeding Disorders

Introduction: Antifibrinolytics are widely used in the prevention and treatment of bleeding, they can be used as a monotherapy for mild bleeding/minor procedures and as adjunctive therapy in combination with other hemostatic agents for moderate/severe bleeding and major procedures. Tranexamic acid (TXA) and aminocaproic acid (6-ACA) are the only agents licensed for at-home administration. TXA is available in tablet and intravenous dosage forms, while 6-ACA is available in tablet, oral solution, and intravenous dosage forms. 6-ACA oral solution (AAOS) is the only commercially-available option for those who cannot swallow tablets, however, barriers to its use include insurance denial and high cost/copayment. TXA tablets can be crushed and mixed into an aqueous solution and is stable for up to 31 days³, thus crushing a tablet into water for immediate use should not affect its efficacy. We report our experience using crushed tranexamic acid tablets in water (cTXAw) in young patients with bleeding disorders.

Methods: In this single-center, IRB-exempt retrospective chart review at Mayo Clinic Rochester, MN eligible patients were less than 10 years of age and who had been prescribed any formulation of TXA from December 2018 to July 2022. For patients prescribed cTXAw, data collection included age, sex, TXA dose, indication for use, clinical outcome, and side effects attributed to cTXAw. Bleeding outcomes were defined as major, clinically relevant non-major, and minor bleeding according to ISTH criteria.

To create the cTXAw, a TXA 650 mg tablet was crushed and dissolved in 10 ml water resulting in a 65 mg/ml solution. Once dissolved, patients/caregivers were instructed to immediately draw up and administer the appropriate weight-based dose and then discard the excess cTXAw. The procedure was repeated with each dose.

Results: Our electronic medical record search identified 666 patients who received TXA of whom 32 were prescribed cTXAw, of whom 7 were prescribed tranexamic acid to be used on as needed basis and it was not used. The remaining 25 had documented use of the medication (table 1); median age was 3 years ( 10 days - 9 years ) and 19 (76%) were male. Bleeding disorders included: von Willebrand disease (52%), hemophilia (20%), Factor VII deficiency (12%), inherited platelet disorders (8%), and immune thrombocytopenia (8%). Twenty-five patients received 32 courses of cTXAw for 21 procedures and 11 bleeding events for a mean duration of 6 days (1 - 14 days). Most patients received 25 mg/kg (28/32, 88%), the rest received 10 mg/kg (4/32, 12%). TXA was used as monotherapy in 24 occasions (75%; 15 procedures and 9 bleeding events) and as adjunctive therapy in 8 (25%; 6 procedures and 2 bleeding events); 6 received factor replacement and 2 received DDAVP.

Type of factor and indication included: FVIII for circumcision (n=2), VWF concentrate for tonsillectomy and adenoidectomy (n=2), FVIII for oral bleeding (n=1), VWF concentrate for hypospadias repair (n=1). None of the 21 procedures (5 circumcision, 5 dental procedures, 5 myringotomy tube placement, 3 tonsillectomy and adenoidectomy, 2 endoscopies, 1 hypospadias repair) were complicated by bleeding as defined by ISTH criteria.

Out of 11 bleeding events (4 oral bleeding, 4 frequent epistaxis, 2 hematomas, 1 laceration), 9 had effective hemostasis with the use of cTXAw (82%), one had no response (9%; used for recurrent epistaxis in addition to DDAVP), one had no reported outcome (9%). None of the patients reported side effects from using cTXAw.

Using tranexamic acid represents a significant cost savings to families and the health care system. The median age of patients in this study was 3 years of age, and the average 3-year-old weighs 14 kg⁴. Average wholesale price (AWP) for TXA is $5.21 per 650 mg tablet, thus a course of cTXAw at 25 mg/kg/dose (350 mg) every 6 hours for 6 days costs AWP $125. A similar regimen using 6-ACA is 50 mg/kg/dose (700 mg) every 6 hours for 6 days⁴. The AWP for 6-ACA is $13.47 per mL of the 250 mg/mL oral solution. For the same 3-year-old, a course of therapy of 6-ACA oral solution costs $905. Of our 13 patients who had also been prescribed AAOS before cTXAw, 8 (61.5%) patients were documented as unable to receive the AAOS due to either prohibitive cost or insurance denial.

Conclusions: Crushed TXA tablets in water (cTXAw) appears to be effective, safe, and cost-effective for young patients with bleeding disorders.

Pruthi:Instrumentation Laboratory: Honoraria, Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer Healthcare AG: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy.