The occurrence of venous thromboembolism (VTE), consisting of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), in athletes has been described in case reports and small case series.^1-3 VTE is common in the general population, and athletes are often subject to trauma, immobilization after trauma or surgery, frequent long-distance travel, and other factors which increase risk for VTE.^4,5

Stepwise resumption of noncontact athletic participation has been proposed beginning as early as 3 weeks after VTE, and full return to noncontact activity can be achieved while the athlete remains anticoagulated.^6,7 Yet there is little guidance in the literature for managing VTE in athletes who participate in contact sports, and this guidance is based on expert opinion and "conventional wisdom" which developed when options for anticoagulation therapy were fewer.7

It has been taken for granted that participation in contact sports during anticoagulation therapy is unsafe, but no publication has considered how pharmacokinetic/pharmacodynamics (PK/PD) profiles of novel anticoagulants may alter this paradigm. A "one-size-fits-all" approach does not account for modern resources that allow individualization of treatment to an athlete's specific needs.

There are four available direct oral anticoagulants (DOACs): apixaban, dabigatran, edoxaban, and rivaroxaban. While each DOAC is different, they share some properties that allow consideration of patient-specific treatment. These properties include rapid onset of anticoagulant action and rapid elimination, yielding a "fast on/fast off" profile.

Combined with thoughtful timing of dosing and careful judgment, and after the initial period of treatment for acute VTE is complete, this allows for a promising scenario: with expert medical guidance, an athlete can schedule medication dosing to maximize therapeutic time while allowing plasma drug levels to fall below an acceptable threshold before sports participation. Therapy is then promptly re-initiated once risk for trauma or bleeding sufficiently normalizes.

Individualized treatment could allow for participation in contact sports while requiring anticoagulation, if desired by the athlete. Potential benefit is most pronounced for elite athletes, as financial and competitive stakes are often high.

Risk of recurrent VTE and fatal recurrent VTE must be considered when assessing any anticoagulation strategy. For individuals who complete anticoagulation treatment for an acute episode of unprovoked VTE, the rate of recurrent VTE over the next 5 years without anticoagulation is 30%.⁸ The rate of fatal recurrent VTE for individuals who discontinue anticoagulation after completing initial therapy is 0.3/100 patient-years.⁹ This suggests that, once initial anticoagulation therapy is completed, risk of recurrent VTE is <1/6000 per day and of fatal recurrent VTE <1/100,000 per day if not on anticoagulation. These absolute risks are very low.

Bleeding is another concern for athletes receiving anticoagulation. Plasma drug levels can be measured for DOACs, but the levels below which the risk of bleeding is not increased are poorly defined. PK/PD studies can provide guidance, but without published data showing specific safe plasma levels, one has to rely on expert opinion consensus to determine a level that appears safe. It is unknown how the risk of bleeding with a very low DOAC plasma level compares to that for aspirin and nonsteroidal anti-inflammatory drugs, which impair hemostasis yet are frequently used by athletes.

Additionally, there is no data to guide physicians regarding when it is safe to resume anticoagulation after competition. While resumption 1-2 hours after an uncomplicated sporting event is likely safe, individualized management decisions need to be made in the event of significant trauma or injury sustained. Delay in re-initiation of anticoagulation or use of only prophylactic anticoagulant doses may be necessary, which may incrementally increase risk for recurrent VTE.

Compared to complete removal from contact sports, the risk for recurrent VTE and bleeding is likely higher if an athlete participates utilizing an individualized intermittent anticoagulation regimen. All athletic activity and medical treatment comes with risk. However, with appropriate management the absolute risk increase can be kept low. The core ethical principle of patient autonomy mandates that we should review reasonable options with an athlete and allow him/her to be a major participant in management decisions factoring in the level of risk he/she is willing to accept.

Implementation of an individualized intermittent anticoagulation program is labor-intensive. Completion of personalized PK/PD studies is not practical in the general population, but for professional athletes with adequate resources, the benefit-cost ratio may be favorable.

More PK/PD studies are needed to allow even safer and more evidence-based treatment plans. Physical characteristics of elite athletes often differ from the general population (e.g., extreme height), and more knowledge is needed regarding how these differences affect VTE risk and DOAC efficacy and metabolism. A registry of elite athletes requiring anticoagulation therapy could help.

We propose that athletes do not necessarily need to be prevented from competing in contact sports while being anticoagulated. With DOACs now available, after obtaining PK/PD data for a specific athlete, an individualized treatment plan can be developed to allow for participation with only a small increase in risk. The athlete, with expert medical guidance, should be allowed to decide whether the benefits in his/her specific circumstances outweigh the risk.

References

1. Tao K, Davenport M. Deep venous thromboembolism in a triathlete. J Emerg Med 2010;38:351-3.
2. Chandra V, Little C, Lee JT. Thoracic outlet syndrome in high-performance athletes. J Vasc Surg 2014;60:1012-7.
3. Sanz de la Garza M, Lopez A, Sitges M. Multiple pulmonary embolisms in a male marathon athlete: is intense endurance exercise a real thrombogenic risk? Scand J Med Sci Sports 2016. [Epub ahead of print]
4. ISTH Steering Committee for World Thrombosis Day. Thrombosis: a major contributor to global disease burden. Thromb Res 2014;134:931-8.
5. Meyering C, Howard T. Hypercoagulability in athletes. Curr Sports Med Rep 2004;3:77-83.
6. Roberts WO, Christie DM. Return to training and competition after deep venous calf thrombosis. Med Sci Sports Exerc 1992;24:2-5.
7. Depenbrock PJ. Thromboembolic disorders: guidance for return-to-play. Curr Sports Med Rep 2011;10:78-83.
8. Kearon C, Akl EA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood 2014;123:1794-801.
9. Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010;152:578-89.

Keywords: Anticoagulants, Athletes, Antithrombins, Hemostasis, Pulmonary Embolism, Pyrazoles, Pyridines, Venous Thromboembolism, Venous Thrombosis

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