Personalized Long-Term Anticoagulation Treatment for a High-Level Athlete

Athletes requiring long-term anticoagulation are usually prohibited from participating in contact and collision sports, significantly impacting their career aspirations. The risk of recurrent venous thromboembolism (VTE) in patients with a history of unprovoked VTE, after completing three months of initial anticoagulation therapy and then discontinuing it, is calculated to be less than 1/3500 per day. (Moll, S., et al, 2018 ) This suggests a low risk of thrombotic events during intermittent interruptions of anticoagulation and may allow for adjustment of anticoagulation therapy to match the athlete's needs.

A 22-year-old male high-level United States college basketball player presented with multiple bilateral pulmonary emboli (PE) without provoking VTE risk factors or personal or family history of thrombosis. Echocardiogram showed no right ventricular strain. Routine laboratory evaluation was unremarkable. Thrombophilia testing was positive for Protein C deficiency by repeated decreased protein C activity (antigen levels at 57% and 56%, respectively (Ref>70%) and genetic testing (demonstrating variant of uncertain significance in PORC gene; PROC NM_000312.3)

To avoid jeopardizing the patient's career prospects as a potential National Basketball Association (NBA) player an individualized intermittent anticoagulation management with Apixaban was discussed. After an initial 3 months of uninterrupted Apixaban therapy with avoidance of contact practices and games, a pharmacokinetic (PK)/pharmacodynamic (PD) study was done while on apixaban 5 mg q 12 hrs. The patient took his morning dose of Apixaban, then had blood draws 1,2, 8 and 24 hours after last intake of Apixaban. Apixaban plasma levels were determined with an Apixaban-calibrated anti-Xa assay. While it is not known at what blood direct oral anticoagulant (DOAC) level the bleeding risk with athletic contact activities is the same as when not on a DOAC, a level of < 30 ng/mL has been suggested in the past (Moll S. et al 2018) and was used in the development of a management strategy for this athlete. The PK/PD study in him showed that a plasma level of < 30 ng/mL was reached between 4 and 8 hours after last intake of Apixaban 5 mg (or 2.5 mg), likely around 5 hours after intake.

An intermittent Apixaban administration plan was developed for him by Hematology in relation to contact training and games, making sure he was off anticoagulation for at least 5 hours before significant physical contact activities during practices or games. The plan was discussed and implemented in multi-disciplinary fashion with the athletic trainer and team physician to minimize and manage contact injury. Given the relatively low peak Apixaban plasma level (around 62.7 ng/dL) in this patient, short half-life (of about 2 ½ hours), and short time to reach a level < 30 ng/mL (about 5 hours), it was easy to develop a personalized anticoagulation management plan for this athlete. Given that his team's practices took place after 1:00 PM during the week, he was able to take Apixaban at 7:00 AM every day from Monday to Friday. None of the 7:00 PM evening dose intake was affected by his athletic activities. On Saturdays he would skip the morning dose, given a team practice in the morning hours. There was no practice on Sundays. Thus, most of the times he was able to take 13/14 (93 %) of all Eliquis doses per week.

Post-training and post-game evaluations by the team physician ensured prompt assessment and management of any contact injuries, and omitting consecutive Apixaban doses if necessary. This enabled the patient to continue playing college basketball for his remaining 3 years and then pursue a career as a professional basketball player, without complications from bleeding or thrombotic events 4 years later.

This case illustrates the potential to create an intermittent anticoagulation regimen for high-level athletes based on a personalized PK/PD study which guides timing of anticoagulant drug intake in relationship to contact athletic activities. Although bleeding and clotting risks remain unclear, as does the minimal plasma DOAC level below which bleeding risk is not increased compared to not being on an anticoagulant at all, a personalized PK/PD studies canto enable some athletes to return to their contact and collision sports despite having an indication for long-term anticoagulation.

Glenzer:Regeneron: Consultancy, Honoraria; Pfizer: Consultancy, Research Funding; Biomarin: Consultancy, Honoraria; Bioverativ/Sanofi: Consultancy, Research Funding; CSL-Behring: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria; Sparx Therapeutics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Hematherix LLC: Other: Co-founder.