Sports Med (2015) 45:1365–1372 DOI 10.1007/s40279-015-0360-5

CURRENT OPINION

Venous Thromboembolism in Physically Active People: Considerations for Risk Assessment, Mainstream Awareness and Future Research Claire M. Hull1 • Julia A. Harris2

Published online: 17 July 2015 Ó Springer International Publishing Switzerland 2015

Abstract The global healthcare burden of venous thromboembolism (VTE) and associated comorbidities (e.g. obesity, heart disease and cancer) is significant. Physical activity—especially cardiovascular exercise—is popularly acclaimed for gold-standard prevention. Paradoxically, intensive training can expose athletes to several potentially thrombogenic risk factors (e.g. heat stress, dehydration, blood vessel injury and inflammation). However, awareness regarding the risk of VTE in physically active people is generally lacking. Given that the overall incidence of asymptomatic and/or occult blood clots that resolve spontaneously is uncharted, and because symptoms and sequelae are not always ‘textbook’, triage evaluation and diagnosis of VTE at large can be challenging. Front-line clinical evaluations, including the major Wells scoring criteria, are (versus the total number of possible factors and diagnoses) comparably reductionist, and the point at which a minor risk might be considered significant in one person—but not in another—is subjective. Considering the popular associations between VTE and inactivity, athletes might be at greater risk of a missed diagnosis quite simply because their cardiovascular conditioning presents as the polar opposite to standard assessment criteria. Undoubtedly, risk factors for VTE associated with exercise are not unique to cardiovascular training or athletes, but the extent to which they might increase the chances of blood & Claire M. Hull [email protected] 1

Institute of Life Science 1, Swansea University Medicine, Swansea SA2 8PP, UK

2

University Health Centre, Penmaen Residence, Swansea SA2 8PG, UK

clot precipitation in certain participants warrants attention. A multi-agency approach, including research to inform mainstream understanding and awareness about risk factors for VTE in patient groups across age, comorbidity and activity spectra, is required. In this article, the potential for pre-participatory thrombophilia screening, haemostatic monitoring and personalized prophylactic guidelines is discussed.

Key Points Venous thromboembolism (VTE) is widely associated with immobility, and physical activity— especially cardiovascular exercise—is popularly perceived as a gold-standard preventative measure, increasing the heart rate, mitigating circulatory stasis, promoting cardiopulmonary conditioning and aiding the maintenance of healthy body weight. Paradoxically, intensive cardiovascular exercise is associated with multiple potentially thrombogenic risk factors; VTE can and does occur in athletes, but overall prevalence data, mainstream awareness and evidence-based preventative guidelines are lacking. The extent to which cardiovascular exercise might heighten the chances of blood clot precipitation in certain participants—especially those with underlying but undetected hereditary thrombophilia(s)—warrants research attention that will ultimately improve the design, intensity parameterization and implementation of safe, sustainable exercise regimens for individuals across age, comorbidity and activity spectra.

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1 Introduction The potential benefits of physical activity for the prevention and management of numerous chronic health conditions, including pulmonary disorders, obesity, diabetes, cancer, psychological stress and depression, are increasingly well documented and highly topical [1]. However, exercise guidelines remain widely debated [2, 3] not least because the types, regimens and intensity of physical activities pursued within the population at large are extremely varied. As we move into the era of personalized healthcare, more specific information and exercise guidelines for individual participants and patient groups will be needed; athletes, prospective enthusiasts and physically active people who want to maintain exercise throughout life or who aim to increase their cardiovascular fitness capacity—through increasingly intensive training regimens—are no exception. In trained athletes, cardiovascular ill-health is often associated with cardiac disorders resulting from the effects of intensive exercise on the heart structure and electrophysiology; these include atrial fibrillation, arrhythmia, neuro-cardiogenic syncope, athlete’s heart syndrome and hypertrophic cardiomyopathy [4]. Public interest surrounding media reports of sudden cardiac events in sportsmen and sportswomen is always high, but popular awareness and understanding about vascular pathologies— excepting those associated with underlying disease [e.g. arterial coronary thrombosis (ACT)] [5–7]—remains relatively poor. Like numerous other vascular conditions (e.g. angina, myocardial ischaemia and varicose veins), ACT is usually linked to predisposing health, hereditary and lifestyle factors (e.g. atherosclerotic heart disease, vascular malformation, sedentary living and diet) and not to the consequences of cardiovascular exercise per se. The problem of blood clots and venous thromboembolism (VTE)—which can be associated with risk factors that relate directly to effects of exercise—is not well documented or widely acknowledged beyond the medical literature [8, 9]. The following article focuses specifically on the awareness, assessment and management challenges that relate to the risk of VTE in athletic individuals. In the first instance, popular awareness and perceptions (including possible misperceptions) about the risk factors for VTE in physically active people are considered (see Sects. 2, 3) and are illustrated using three case scenarios (see Sect. 4). Factors that might compound or exacerbate the challenge of assessing the risk of VTE in athletes and non-athletes are discussed (see Sect. 5), followed by a brief look at the

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bigger health picture surrounding the prescription of exercise for the management of health comorbidities, many of which are risk factors for VTE (see Sect. 6). Questions and frontiers for future research and the need to heighten both medical and mainstream awareness about VTE in the age of personalized healthcare are highlighted (see Sect. 7).

2 Blood Clots and Inactivity: Popular Understanding and Awareness Deep vein thrombosis (DVT) has been dubbed the ‘economy-class syndrome’ through popular association with long-haul flights, cramped seating and inactivity [10]. Today, the problem of ‘eThrombosis’ resulting from prolonged periods of immobility—sitting in front of personal computers and game consoles—is an emergent concern [11]. Physical activity—especially cardiovascular exercise—is widely perceived as a gold-standard preventative measure, increasing blood flow and improving circulation (mitigating circulatory stasis) while also aiding maintenance of healthy body weight. The positive effects of exercise on overall vascular health (e.g. reduced blood pressure, increased activity of antioxidant enzymes, reduced oxidative stress and restored vascular endothelial function) are also important [12, 13] because good vessel conditioning can help mitigate the risk of VTE. At a time when the global healthcare burden of illness and comorbidity associated with obesity and sedentary living—including that of VTE [14]—continues to escalate, discussion of the risk factors for VTE in athletic people sounds almost inappropriate. But it should not be. Here, a critical appraisal of Virchow’s triad (circa 1854) [15] in light of contemporary knowledge regarding VTE indicates that physically active people—and quite possibly especially those who pursue cardiovascular exercise—can be exposed to multiple, potentially thrombogenic risk factors (Fig. 1) [8]. In any one person, these might include sweating, dehydration and electrolyte imbalance (leading to blood hypercoagulability), injury and inflammation (relating to endothelial microtrauma and vessel damage), and bradycardia (owing to high cardiopulmonary fitness), which could contribute to or exacerbate circulatory stasis, particularly at rest. Here, review of the sports medical literature reveals that blood clots can and do occur in athletes [16–26], but that the overall incidence and relative importance of risk factors for VTE in active people remain uncharted—and this is not a trivial issue.

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HYPERCOAGULABILITY Major surgery / trauma1 Malignancy1 Pregnancy (post-partum) Inherited thrombophilia (e.g., antiphospholipid syndrome, prothrombin mutation, protein S, protein C & factor V Leiden) • Infection and sepsis • • • •

• • • • •

Inflammatory bowel disease Nephrotic syndrome Oestrogen contraceptives Inflammation Heat stress, electrolyte imbalance & dehydration • Autoimmune conditions • Psychological stress • Changes in blood physiology after physical exercise

CIRCULATORY STASIS

VASCULAR DAMAGE • • • • • •

Thrombophlebitis Cellulitis Atherosclerosis & heart disease Indwelling catheter or heart valve Venepuncture Physical trauma, strain or injury (occupational, sports & training)

• Immobility or prolonged inactivity1 • Venous obstruction or restriction1 (e.g., obesity, tumour, pregnancy) • Varicose veins • Atrial fibrillation • Left ventricular dysfunction • Bradycardia & hypotension • Congenital structural malformations (e.g., May-Thurner & thoracic outlet syndromes)

VTE

DVT Wells score criteria Clinical feature

PE

Score

Wells score criteria

Active cancer (treatment ongoing, within 6 months, or palliative)

1

Clinical feature

Paralysis, paresis, or recent plaster immobilization of the leg

1

Clinical signs and symptoms of DVT (minimum of leg swelling and pain

Recently confined to bed for ≥3 days or major surgery within 12 weeks requiring general or regional anesthesia

1

with palpation of the deep veins)

Localized tenderness along distribution of deep venous system

1

An alternative diagnosis that is less likely than PE

Entire leg swollen

1

Heart rate >100 beats/min

1.5

Calf swelling at least 3 cm larger than asymptomatic side

1

Immobilization for >3 days or surgery in the previous 4 weeks

1.5

Pitting edema confined to the symptomatic side

1

Previous DVT or PE

1.5

Collateral superficial veins (non-varicose)

1

Haemoptysis

1

Previously documented DVT

1

Malignancy (on treatment, treated in the past 6 months or palliative)

1

2An

-2

Total score: ≤4 = PE unlikely

alternative diagnosis at least as likely as DVT

Total score: ≤1 = DVT unlikely

Score

3

3

>4 = PE likely

≥2 = DVT likely

Fig. 1 Triad summary of risk factors for venous thromboembolism (VTE). The underlined factors relate directly to the effects of physical activity, training injuries and/or cardiovascular endurance fitness; potential VTE risks from other health conditions and comorbidities are listed. Risks associated with physical exercise and training are

present in all three sections of the triad. 1Existing Wells score criteria [27, 28]. 2Wells DVT score criterion that is possibly most applicable to physically fit and active patients presenting with differential diagnoses. DVT deep vein thrombosis, PE pulmonary embolism

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3 Cardiovascular Fitness and Athleticism: Polar Opposites to Clinical Venous Thromboembolism Risk Evaluations? In triage departments and initial assessment / minor injury units, standard fast-track protocols and scoring tools (e.g. the Wells criteria) are employed to determine risk scores for DVT [27] and pulmonary embolism (PE) [28]; the suitability of these evaluations for athletes and physically fit patients has not been documented. This is significant because often the cardiopulmonary characteristics [low pulse rate, hypotension, high respiratory efficiency and maximal aerobic capacity (VO2 max)] and physical conditioning (high muscle tone and low-percentage body fat) of athletic people are atypical of the adult population at large and might even (a) mask classical diagnostic signs of VTE and/or (b) enable athletes to compensate for the presence of clots (see Sect. 4). Regarding the risk of a missed diagnosis of VTE in certain patient groups (e.g. active young people), it is important to note that the reason why a diagnosis of VTE may be missed (or approached with a low index of suspicion) may not be exclusively related to exercise but may be related to the fact that the a priori risk of VTE in the young is generally very low. After initial Wells score assessment, follow-up D-dimer testing in cases of suspected VTE based upon Wells score outcomes is a standard practice [29]. However, the likelihood of obtaining false positives in physically active people and sports enthusiasts who might be considered as presenting with a training injury (e.g. a muscle tear, sprain, or tendon or ligament damage) can be a complicating factor. In certain cases where Wells scores are found to be insignificant (e.g. a total score of B1 = DVT unlikely; a score of B4 = PE unlikely), D-dimer testing might not even be pursued. Medical ultrasonography (usually Doppler or duplex scanning) widely remains the simplest and most cost-efficient way to diagnose the actual/physical presence of one or more DVTs in lower and upper extremity limbs. Here, the potential benefits and limitations of point-of-care (POC) ultrasound and portable ultrasonography devices for patient assessments undertaken in triage, primary care and sports practitioner settings remain under debate. POC ultrasound is not yet standard practice, not least because identification of DVT via ultrasonography requires high levels of specialist training, clinical judgment and practitioner skill; some clots can be missed by even the most experienced ultrasonographer. Computerized tomography (CT) scanning with intravenous contrast is widely employed as the principal diagnostic imaging modality for evaluation of suspected PE [30, 31]; it can also be applied to investigation of DVT, which may not occur in the lower

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or upper limbs. Other imaging techniques include magnetic resonance (MR) angiography, invasive pulmonary angiography, ventilation–perfusion (V/Q) lung scanning, and transthoracic and transoesophageal echocardiography (TTE and TEE). However, these modalities are not always time or cost efficient, nor are they readily available for routine and POC assessments. Considering the numbers of risk factors, signs, symptoms and differential diagnoses for VTE (Fig. 1), the assessment task facing triage practitioners is far from enviable. Given popular associations between VTE and inactivity, athletes might be even be considered at higher risk of a missed or delayed VTE diagnosis [18, 20, 23] quite simply because their cardiovascular fitness and related physiological and anatomical (including vascular) conditioning physically present as polar opposites to the major risk factors comprising clinical VTE assessment protocols. Several case reports [16–26] have highlighted that atypical symptoms and unusual sequelae are recurrent issues in athletes, for whom VTE is initially considered with a very low index of suspicion. Undoubtedly, the challenges surrounding diagnosis of VTE are not limited to athletes, and a consideration of the clinical situation at large (see Sects. 5 and 6) underscores the reality that the classical presentation of VTE symptoms and sequelae is rarely ‘textbook’; even the very best clinical protocols and judgment may not point towards VTE in cases where it is actually present. Nonetheless, it is arguable that heightened medical and mainstream awareness about the potential risk factors for VTE in physically active people could—in some cases—help avert delayed or missed diagnoses.

4 Venous Thromboembolism in Physically Active People: Three Case Scenarios Consider first a trained endurance athlete with excellent physical conditioning, mental resilience and the determination to push through (rather than succumb to) pain, who exhibits high cardiopulmonary fitness [a bradycardic pulse (45 beats/minute) and hypotension], presenting with shortness of breath and harbouring multiple pulmonary microemboli. Even a doubling of their resting heart rate does not meet the Wells score threshold for PE ([100 beats/minute); exercise-induced asthma, allergy, chest infection, anxiety, anaemia and hypothyroidism are all plausible diagnoses. Following the results of a clear X-ray—a notoriously limited discriminator/diagnostic for PE [30, 31]—the athlete returns to training unaware of the possible health risks that this might confer. Second, a racket sports player with a history of lateral epicondylitis (tennis elbow) presents with breathlessness

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and lower leg pain following an intensive training session in hot conditions on a hard court; they liken calf discomfort to tendonitis. Unaware (or perhaps unconvinced) about their potential risk factors for DVT, they follow general advice from friends and implement RICE (rest, ice, compression and elevation) steps [32]. Interestingly, the first two of these (rest and ice) might actually exacerbate an underlying problem of DVT; the latter two (compression and elevation) can help alleviate its symptoms. In this scenario, the possible differential diagnoses are numerous and could relate to injuries from overuse and training errors [33, 34]. Aside from tendonitis, these include fascial defects, chronic exertional compartment syndrome, stress fractures, musculotendinous junction disruptions (tennis leg), popliteal artery entrapment syndrome [35], medial tibial stress syndrome, nerve entrapment and, finally, effort-induced venous thrombosis. Here, it is worth noting that while symptoms of DVT might be expected to present before (or in conjunction with) PE, very often people present with PE without obvious leg pain or evidence of DVT. Furthermore, blood clots can and do occur in any deep vein (e.g. axillary vein thrombosis), and accounts of upper extremity DVT have been reported in athletes presenting with exertional thrombosis [16]. Finally, a stressed office worker has an undiagnosed hereditary thrombophilia [36] and signs up to a local gymnasium and cardio-fitness classes, intent on losing weight and achieving the popularly acclaimed benefits of the ‘endorphin rush’. Without training experience and/or vigilance regarding hydration, and spurred into action by reaching targets quickly (e.g. through initial and rapid loss of water weight), they discount the cramp-like pain behind their kneecap as a pulled muscle (without considering the risk of popliteal DVT) and resign themselves to rest and inactivity. In all of these cases, the insidious threat and potential consequences of VTE increase the longer a medical diagnosis is not made or even sought.

5 Physical Activity and Thromboembolic Events Documented risk factors for VTE are diverse, and it is has long been accepted that the relative importance of each is difficult—and, in some cases, even impossible—to establish with certainty [37]. Perhaps one of the most obvious questions regarding the risk of VTE in athletes and physically active people is: at what point should (or might) cardiovascular exercise be regarded as a protective or precipitating factor? In secondary care, the development of VTE is classically linked to prolonged periods of physical immobility following major illness, trauma and surgery. As such,

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immobilization is recognized as a major risk factor in the Wells scoring criteria for DVT and PE [28, 29]. Conversely, in community settings where people are more mobile and—very often—really quite active (e.g. in physically demanding occupations or through training and exercise), the occurrence of thromboembolic events, including PE, can be attributed to an underlying DVT or a blood clot that has been actively dislodged from one site (often the lower leg) and transported—via the circulatory system—to narrower blood vessels in the lungs. In view of the evidence for exercise-induced plaque rupture and arterial thrombosis in athletes [5–7], it stands to reason that one might question if certain athletes could be at greater risk of exercise-induced VTE. The extent to which cardiovascular exercise might (a) exacerbate precipitation of blood clots and/or generation of emboli (e.g. from an undiagnosed DVT) or (b) act in a compensatory way—by accelerating natural clot degradation processes—is unclear. It has been reported that strenuous exercise can induce blood coagulation (clot formation) while simultaneously enhancing blood fibrinolysis (clot breakdown), but that the extent of this equilibrium depends on exercise intensity and duration [38]. Moderate exercise intensity is believed to activate fibrinolysis without coagulation, while very intensive exercise is associated with concurrent activation of both blood coagulation and fibrinolysis (see El-Sayed et al. [38]). Further research suggests that the magnitude of the fibrinolytic response is ultimately related to the resting fibrinolytic profile of individual people [39]; it has been demonstrated that responses to acute exercise can increase the risk of coagulation in certain individuals [e.g. those with cardiovascular disease (CVD)], but that chronic aerobic training could serve to decrease the coagulation potential and increase the fibrinolytic potential in both healthy subjects and CVD sufferers [39]. It is believed that chronic aerobic exercise training could result in favourable adaptations that ultimately contribute to decreased risks of ischaemic and thrombogenic events both at rest and during physical exertion. But the information needed for comprehensive understanding and for design and prescription of suitable exercise regimens does not end there. The risks associated with underlying (and often undiagnosed) genetic thrombophilias [36, 40] and comorbidities (see Sects. 6 and 7) are compounding issues.

6 Exercise, Health Comorbidities and Venous Thromboembolism: The Bigger Picture The extent to which undiagnosed and lesser-studied comorbidities might add to (or perhaps even exacerbate) the risk of VTE in physically athletic people and those who

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are now being encouraged to pursue more active lifestyles is not fully understood; this warrants attention. VTE is already known to be a complication of active malignancy and can also indicate the presence of occult disease [40]; cancer is listed as a major risk criterion in Wells score assessments for both DVT and PE [28, 29]; consequently, specialized and carefully monitored exercise regimens for cancer sufferers are required. The prevalence and risks associated with undiagnosed malignancy and intensive physical training are, however, uncharted. Studies detailing how changes in blood chemistry that occur following physical activity and in response to acute psychological stressors can lead to a hypercoagulable state [41, 42] are also important because physical exercise is increasingly recommended for management of stress and depression. Here, it is worth noting that research studies of the psychological and physiological effects (including effects on blood chemistry) and consequences of exercise are often undertaken independently of each other. For example, recent research has detailed the mental health benefits of physical activity in women with polycystic ovary syndrome (POS) [43]. However, results from population-based matched-cohort analysis have also indicated that there might be an increased risk of VTE in women with POS [44]. The growth of evidence regarding psychobiological relationships between hypercoagulability and autoimmune conditions [45] and post-traumatic stress [46] is also interesting because exercise therapies are encouraged for the management of both. Work is now required to consolidate findings from existing studies of the psychological and physiological effects of exercise across patient groups characterized by different comorbidities. Perhaps one of the most important issues is how the effects of physical exercise might influence the clotting cascade in individuals with underlying hereditary thrombophilia(s) that may remain undiagnosed or that might be detected only via genetic thrombophilia screening after a thrombotic event has occurred; this warrants research investment. For those possessing a priori knowledge of a thrombophilic condition [e.g. antiphospholipid syndrome (APS)], prophylactic anticoagulant therapy is often advisable [47], and research focusing on the management of the APS and exercise has been documented [48]. More specific guidelines and exercise prescriptions for those with other hereditary thrombophilias require further parameterization. Aspirin has long been recognized as a general preventative measure [49], but its benefits must be weighed against patient-specific risk factors. Precautionary physical measures, including use of compression hosiery (e.g. class II stockings worn during long-distance travel) are also valuable for individuals who have suffered DVT and for prevention of post-thrombotic syndrome.

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7 Venous Thromboembolism and Personal Exercise Regimens: Frontiers and Future Challenges As we move into the era of personalized healthcare, with an emphasis on holistic and individual lifestyle choices, more information regarding the potential risks, prevention, detection and management of VTE in physically active people—across the age, comorbidity and activity spectra— will be needed. This will necessitate a multi-agency approach. In the first instance, increased awareness and vigilance regarding the problem of VTE in atypical individuals is required. Blood clots can and do occur in physically active people (including very active athletes and sportspersons), and this must be recognized through dialogue between medicine and sports medicine—at both the research and practitioner levels—and ultimately through clearer guidelines for the fitness industry and the public at large. Evidence-based and accessible mainstream media—produced not to scaremonger but to engage and enable people to make informed decisions about their own healthcare and fitness regimens—will be key. Regulation within the fitness industry at large is another consideration. At present, prospective fitness enthusiasts can ‘add gym membership to basket’ via online portals; yet, while pre-participatory fitness screening (typically for cardiac conditions) is often debated [4], it remains neither mandatory nor closely regulated. Importantly, occupational health assessments for CVD patients (e.g. those returning to work after a cardiac event) can and do include electrocardiography (ECG) testing to determine recommendations for physical work. Yet, when it comes to mainstream exercise and health, the traditional caveat has always been to ‘‘seek advice from your doctor’’. But how many people actually do? Thrombophilia screening represents one potential pre-participatory evaluation that could facilitate identification and prescription of suitable fitness regimens and management advice for affected athletes and prospective enthusiasts. For active people who have no major (age, environmental, hereditary or comorbidity-related) risk factors for VTE, avoiding dehydration is perhaps one of the most obvious precautionary measures. However, while popular advertisements frequently promote sports hydration products and the importance of replenishing fluid and electrolytes—for training performance—the importance of hydration for mitigating the risk of VTE is poorly (if at all) acknowledged. When discussion does arise, clear hydration guidelines parameterized through research—at the level of blood physiology—for different people across the age and activity spectrum are lacking. In fact, despite the existence

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of a lucrative and clear market for sports hydration products, their regulation and benefits for health and fitness remain controversial [50]. A compounding issue is the fact that individual vigilance regarding dehydration (and awareness about its signs and symptoms) varies between individual athletes and non-athletes. Thirst—a clear sign of dehydration—is not always recognized, or (in a training or competitive environment) it might be simply ignored. The consequences of this for the risk of VTE are unspoken. Temperature acclimatization studies have provided important but incomplete insights, often focusing on temperature and exertional extremes. Heat stress and hyperthermia are associated with haemoconcentration, thrombocytosis (an increased number of platelets in the blood) and disseminated intravascular coagulation [51]. At the other end of the spectrum, the coagulation potential can be elevated following exposure to very cold temperatures [52]. In the area of military medicine, well-trained individuals may tolerate hyperthermia without adverse side effects because of training-induced heat acclimatization effects on cellular protective mechanisms (see Veasic´ et al. [53]). Exactly how and if findings from these (and similar) studies might translate to athletes and fitness enthusiasts at large is unclear. It is generally well accepted that regular sports activities (arguably in relatively acclimatized individuals) appear to decrease the risk of venous thrombosis [54], and undoubtedly the benefits of moderate exercise are likely to outweigh the risks of no exercise at all for very many people. However, the VTE risks associated with extremes of exertion in specific patient groups now deserve fuller attention, especially in view of very recent literature illuminating how high-intensity exercise appears to increase the risk of thrombotic events [55]. As we move into an age of personalized healthcare, and as more people are encouraged to pursue physical activity, determining the safe threshold of exercise intensity for different individuals represents a clear challenge for future work.

8 Conclusions With the increasing emphasis on physical exercise and sports participation, there will likely be increases in the number of people with exercise-related cardiovascular complaints, including VTE. Specific research to characterize changes in blood chemistry and coagulation (before, during and after exercise) in people with one or more comorbidities will be required to improve the parameterization of personalized exercise plans and to determine preventative measures for different patient groups. As research into biochemical, molecular biological and clinical approaches to investigations of the haemostatic system [56] continues to advance, so

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too does the potential to identify associations between physical exercise and clinically relevant hypercoagulable states. Frontiers in this area of research include development of blood monitoring devices (akin to heart rate monitors), which permit haemostatic profiling and—for individuals found to be at high risk—interventional measures and therapies to prevent overt thrombotic disease. Compliance with ethical standards CMH held a BEACON Convergence research project contract supported by the Welsh Government and the European Regional Development Fund (ERDF) of the European Union, and was hosted at Swansea University (College of Medicine) at the time of writing this article. Research for this manuscript was not funded by a grant provider. Claire Hull and Julia Harris declare that they have no conflicts of interest relevant to the content of this article.

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Venous Thromboembolism in Physically Active People: Considerations for Risk Assessment, Mainstream Awareness and Future Research.

The global healthcare burden of venous thromboembolism (VTE) and associated comorbidities (e.g., obesity, heart disease and cancer) is significant. Ph...
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