1vascular-iStock79025781Hemostatic activation following a mara­thon is lower in athletes who run with compression socks than those who run with typical athletic socks, suggesting the garments may help reduce the risk of post-exercise clot formation in athletes who travel to events.

By Amanda Zaleski, MSc; and Beth Taylor, PhD

There are several published case studies of athletes who have experienced deep vein thrombosis (DVT), pulmonary embolism (PE), or both following athletic competition or physical activity. Tao and Davenport, for example, reported on a female triathlete who was diagnosed with DVT and PE after competing in a half Ironman triathlon.1 After competing in the triathlon she traveled five hours by car the following morning. She subsequently experienced symptoms of left lower extremity swelling and pain, accompanied thereafter by dyspnea and lightheadedness on exertion. There are also several published cases of DVT and PE occurring after marathon running. Mackie and Webster described two male marathon runners who developed DVT and PE approximately one week after running a marathon; in both cases, DVT was misdiagnosed initially (either as a muscle strain or Baker cyst).2

The myriad benefits obtained from regular sustained exercise are undeniable. However, such case reports indicate that, in at least a small fraction of otherwise healthy avid exercisers, there may be an augmented risk of DVT following endurance exercise.

Car, bus, train, or air travel by an athlete who has recently engaged in endurance exercise may shift the hemostatic balance, increasing the risk of venous complication.

Research has established that strenuous endurance exercise, such as marathon running, activates the coagulatory system (clot formation) by immediately increasing markers of coagulation such as thrombin-antithrombin complex (TAT), prothrombin fragment 1 and 2, and D-dimer.3-5 In response, the fibrinolytic (clot breakdown) system (eg, tissue plasminogen activator [t-PA] antigen and activity) activate in coordination with the coagulatory system following exercise, such that changes in coagulation are paralleled by an activation of fibrinolysis to preserve hemostatic balance. In other words, in healthy athletes, postexercise clot formation is approximately equal to clot breakdown. This phenomenon, by which both markers of coagulation and fibrinolysis are increased in the bloodstream, is termed “hemostatic activation.”

While exercise-induced hemostatic activation is not detrimental for most individuals, factors incident to marathon running may disproportionately activate the coagulatory system, increasing the risk for venous thromboembolism (VTE) and contributing to reports of DVT, PE, or both—all of which have been reported after prolonged strenuous endurance events in otherwise healthy athletes.6-13 Given that marathon participation has increased 40% over the past decade, with 550,637 finishers in 2014,14 this has implications for the increasing numbers of athletes who compete in endurance events.

Risk factors for VTE

1Vascular-shutterstock_65456923The benefits of regular sustained aerobic exercise are indisputable. Paradoxically, endurance training and competition expose athletes to factors that may increase their risk for VTE. Virchow’s triad is composed of three factors—venous stasis, endothelial cell injury, and hypercoagulability—that augment blood clot risk.15 Endurance athletes are exposed to a combination of these factors; they experience repetitive microtrauma, endothelial damage, and dehydration during competition, followed by periods of inactivity, immobility, and stasis while traveling to and from athletic events or recovering from the event.

The superimposition of car, bus, train, or air travel on an athlete who has recently engaged in endurance exercise, for example, may shift the hemostatic balance in athletes postcompetition, thereby increasing the risk of VTE in certain individuals. The MEGA trial reported that any travel by car, bus, train, or plane longer than four hours increases risk of DVT twofold,16 and, indeed, there are several published case reports17,18 and substantial anecdotal evidence on the Internet detailing athletic individuals who have experienced VTE after the combination of competition and travel.19,20 To the best of our knowledge, however, we are the first group to examine the effect of prolonged exercise and air travel on thrombotic risk factors.5,21

We examined 41 time-qualified runners participating in the 2010 Boston Marathon who either flew more than four hours (travel group) or drove less than two hours (control group) to the race. We obtained blood samples to assess coagulation (TAT, D-dimer, P-selectin, and microparticles) and fibrinolysis (t-PA) the day before the marathon, immediately after the event, and the day after the marathon following the flight home.

Baseline TAT, t-PA, D-dimer, P-selectin, and microparticle levels were not different between travelers and controls. Immediately following the marathon, all markers of coagulation and fibrinolysis were significantly higher than baseline, indicating that hemostatic activation had occurred. However, among individuals who flew more than four hours, the increase in coagulation factor TAT from baseline to after the race in the travel group was nearly double the increase seen in the controls (5 ± 4 to 12.9 ± 15.6 mg/L vs 4 ± 1.2 to 6.1 ± 1.2 mg/L; p = .02).

Similarly, exercise-induced increases in D-dimer, a clinical biomarker of DVT, were also significantly greater immediately after the marathon in the travel group of athletes than in controls (142 ± 83 to 387 ± 196 ng/mL vs 85 ± 26 to 233 ± 95 ng/mL; p = .02). In fact, six of the runners in the travel group (vs no local controls) had D-dimer values that exceeded the clinical threshold for preliminary diagnosis of DVT (> 500 ng/mL).22

Most notable, however, was that marathon-induced increases in the fibrinolytic factor t-PA did not differ between control and travelers, indicating a hemostatic shift toward a more procoagulatory state in athletes who flew to Boston and ran the marathon. Moreover, the increase in the TAT response was greatest in the oldest runners (p < .01), and older subjects also had greater P-selectin values (a marker of inflammation) than younger subjects, indicating that age appears to moderate the coagulatory response to endurance exercise in combination with cross-country air travel.

These data provided the first evidence that the combination of marathon running and air travel disrupts the hemostatic balance and favors a coagulatory response, which appears to be exacerbated with increasing age. Other factors specific to endurance athletes that could additionally exacerbate VTE risk include oral contraceptive use, presence/family history of a clotting disorder, sex, injury, bradycardia, atrial fibrillation, or previous history of VTE.15,23,24

Compression socks during a marathon

Figure 1. Researchers obtained venous blood samples from marathon runners the day before the event, immediately after the event, and 24 hours later.

Figure 1. Researchers obtained venous blood samples from marathon runners the day before the event, immediately after the event, and 24 hours later.

The Evidence-Based Clinical Practice Guidelines from the American College of Chest Physicians suggests the use of properly fitted compression socks to mitigate blood clot risk in high-risk populations.25 The use of compression socks, or mechanical prophylaxis, to maintain hemostatic balance has been studied with participants at rest and has been shown to be effective in reducing VTE in some clinical populations (eg, patients with a previous history of DVT or recent surgery),26 but contraindicated in others (eg, patients with arterial insufficiency).27

Awareness of VTE in endurance athletes has grown significantly in the past few years, and, consequently, running associations and events are increasingly urging athletes to wear compression socks during flight and competition to diminish DVT risk.28,29 Although these informal (albeit common-sense) recommendations are grounded in evidence derived from clinical populations, the efficacy of compression socks to attenuate marathon-induced hemostatic activation has been tested only recently.30

Our group recently examined the safety and efficacy of compression socks worn during a marathon on hemostatic activation immediately following the 2013 Hartford Marathon in Connecticut. We randomly assigned runners (n = 20) to a compression sock group or a control group at the initial screening.30 The runners reported to the marathon exposition the day before the event. We obtained venous blood to measure coagulatory factors (TAT, D-dimer), a fibrinolytic factor (t-PA), and hematocrit (Figure 1). We also obtained blood immediately after completion of the marathon in the main medical tent approximately 100 m from the finish line and within 24 hours of the race finish.

Runners in the sock group (n = 10) were compression sock naïve; they received their socks (19-25 mm Hg at the ankle) at the marathon expo and were instructed to wear them to the race start and throughout the duration of the marathon (Figure 2). Runners in the control group (n = 10) were instructed to wear their typical athletic socks, but refrain from compression sock use during training, the marathon, and on the day after the marathon.

Plasma concentrations of D-dimer, TAT, and t-PA did not differ between groups at baseline. Consistent with findings from previous studies, we observed parallel increases in markers of coagulation and fibrinolysis immediately following strenuous exercise, specifically, exercise-induced increases in D-dimer, TAT, and t-PA. Of note, these parallel increases of coagulation and fibrinolysis did not differ between recreational Hartford marathoners and elite Boston marathoners who trained more and performed faster, reinforcing the negligible impact of differences in training history and race time on exercise-induced hemostatic activation. Average t-PA across all three time points was lower in the compression sock group than the control group (p = .04).  Similarly, average TAT across all three time points was lower in compression sock group compared with the control group, with a trend toward statistical significance (p = .07); however, plasma D-dimer did not differ between the groups across all three time points (all p > .2).

Because runners were not wearing compression socks at baseline, and there were no differences in hemostatic markers at baseline between groups, the findings related to t-PA and TAT suggest a significant effect of wearing compression socks on immediate and 24-hour post marathon hemostatic markers—specifically that overall hemostatic activation following a marathon was lower with compression socks than with typical athletic socks. Most importantly, compression socks did not appear to adversely influence markers of hemostasis during a marathon and thus they appear safe for overall use in runners.

Given that prolonged travel (greater than four hours) activates the coagulatory system, and many marathoners travel long distances to an event, the use of compression socks as a preventive measure should be considered, assuming they are tolerable and properly fitted.31 However, the efficacy of compression socks still remains to be tested in combination with travel, as the athletes in this study traveled local, short distances to and from the marathon.

We caution that there is a need for larger studies, as well as studies of hemostatic alterations following a marathon in combination with other risk factors (eg, oral contraceptive use, prolonged travel, and genetic predisposition for VTE).24 We maintain a DVT registry of athletes who have had a history of VTE after competition to better identify individual risk factors that may contribute to this phenomenon.

Performance, recovery and VTE risk

Figure 2. Runners in the sock group were given compression socks and instructed to wear them throughout the duration of the marathon.

Figure 2. Runners in the sock group were given compression socks and instructed to wear them throughout the duration of the marathon.

Athletes wear compression socks for a variety of reasons beyond reduction of blood clot risk, and thus their influence on noncoagulatory outcomes deserves further mention. Compression socks are increasingly popular with athletes due to perceived enhancement of exercise performance and recovery. To date, the research regarding the efficacy of compression socks to enhance performance, aid in recovery, or both has been equivocal.32-36 This is partially due to the difficulty of conducting placebo-controlled trials and the use of subjective qualitative reporting as primary outcome measures. Studies that have measured objective physiological markers of muscle damage (ie, creatine kinase, a marker of muscle damage, and lactate, a metabolic byproduct) have been limited and inconclusive, perhaps because the studies are vastly heterogeneous in terms of a) the type of compression garment used (eg, whole body, sleeves, knee-high compression) and b) the modality of exercise being tested (eg, resistance or aerobic).

Hypothetical mechanisms underlying performance and recovery benefits of compression socks differ depending on their timing of use (ie, during or after exercise), but are similar in that all theorize that the mechanism of action targets components of Virchow’s triad.

Compression socks worn during exercise are thought to reduce microtrauma and enhance venous return by applying an external circumferential pressure gradient that reduces swelling space, improves blood flow, and in turn improves performance.37,38

Compression socks worn during recovery are thought to accelerate metabolic waste clearance, attenuate edema and swelling, and improve oxygen delivery to muscle.39,40

A recent meta-analysis incorporating 12 studies found a favorable effect of compression socks for enhancing recovery from muscle damage, based on creatine kinase and reduced severity of delayed onset muscle soreness.33 However, of the studies included in the meta-analysis, not one sought to examine the influence of compression socks in response to a sustained aerobic event (eg, marathon or triathlon), making the interpretation of the findings difficult to apply to endurance athletes.

A separate systematic review concluded the available literature does not fully support or refute the use of compression socks for improving performance or recovery.41 For example, three studies found no difference in running performance while wearing compression socks,35,37,42 while one demonstrated improvements in running speed and performance.43

To the best of the authors’ knowledge, there are only two randomized controlled trials that examine performance and recovery in marathon runners.42,44 One found compression socks worn for 48 hours after a marathon were associated with a 5.9% improvement in functional recovery (ie, time to exhaustion on a treadmill two weeks after a marathon).44 The other reported that compression socks worn during a marathon did not result in better race performance or lower markers of exercise-induced muscle damage, as assessed via serum myoglobin and creatine kinase concentrations before and after the event.42

Conclusion

1Vascular-shutterstock_283319420In conclusion, with the exception of one study,35 the data do not appear to reveal any adverse consequences of compression socks, and in some cases suggest socks may result in psychological advantages that translate into performance gains. Assuming that socks are properly sized, marathoners can consider compression socks a sports garment that has preliminary evidence to support its use for preserving hemostatic balance during exercise and hastening recovery from exercise, but not for enhancing performance.30,42,44,45

Runners should be aware of manufacturer specifications and proper sizing techniques. Although a minimum threshold of pressure applied at the ankle is not yet clearly defined in the literature,46 compression socks should be graduated (ie, lower pressure at the ankle gradually increasing to higher pressure at the knee). Lastly, socks should be sized according to calf circumference, not shoe size, to avoid excessive pressure at the calf and to potentially increase the risk-benefit ratio.31 By following these specifications, athletes may be reassured that compression socks likely do not harm athletic performance and recovery, which is critically important given the time and effort associated with training and performance.

Amanda L. Zaleski, MS, is an exercise physiologist in the Department of Preventive Cardiology in the Henry Low Heart Center at Hartford Hospital in Connecticut and a doctoral student in the Department of Kinesiology at the University of Connecticut in Storrs. Beth A. Taylor, PhD, is the director of exercise physiology research in the Department of Preventive Cardiology in the Henry Low Heart Center at Hartford Hospital and an associate professor in the Department of Kinesiology at the University of Connecticut. Her interest in blood clot risk arose from the experience of her older sister, who experienced a DVT and PE after running a half marathon and flying home to Seattle, WA, from Hartford, CT.

Disclosure: Amanda Zaleski has received funding from the CT Space Grant Consortium Graduate Fellowship, Hartford Hospital, and the American College of Sports Medicine NASA Space Physiology Grants for her ongoing research to examine risk factors associated with VTE in active individuals. In addition, she discloses product sponsorship from 2XU Compression Socks.

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