Deep Vein Thrombosis: Causes and Consequences

Q: What are risk factors for deep vein thrombosis in the leg and considerations related to physical activity or exercise?

Deep vein thrombosis (DVT) falls under the umbrella of venous thromboembolism (VTE) along with pulmonary embolism (PE) (¹). Identified as a public health problem, VTE impacts an estimated 300,000 to 600,000 individuals in the United States annually, or between 1 and 2 per 1000 people (²). Although hospital patients may come to mind for VTE risk, anyone can be impacted, even elite athletes, such as tennis star Serena Williams and basketball player Chris Bosh (³).

DVT occurs when there are clots in the deep veins of the body, accounting for about two-thirds of VTE cases; PE occurs when a clot breaks free and moves into the arteries of the lungs, reflecting about one-third of VTE cases (²). PE frequently causes sudden death because of the clot blocking vessel(s) that provide blood to the lungs; signs and symptoms include shortness of breath, rapid heart rate, sweating, and/or chest pain (¹). In contrast, about half of the cases of DVT result in few symptoms; those with symptoms may report pain, swelling, discoloration, or redness in the affected area, along with warm skin (¹). A potential challenge when working with active individuals is that symptoms noted may be difficult to differentiate from activity or sport-related concerns or injuries, such as muscle strain or compartment syndrome (⁴).

Although symptoms may go away after treatment, approximately 30% of individuals have ongoing issues including leg pain/swelling, recurrent skin breakdown, and ulcers, along with increased risk of future DVT (¹). Recurrence has been reported in 30% of patients, with the highest hazard for recurrence within the first 6 to 12 months (⁵). VTE has been suggested to be a chronic disease given the potential episodic recurrence (⁵). Moreover, post-thrombotic syndrome (PTS) is a serious potential consequence of DVT (⁶). See Box 1 for insights related to PTS.

BOX 1. Post-thrombotic syndrome (PTS)

PTS is defined as “a clinical disorder of pain and disability resulting from chronic venous insufficiency following DVT” (⁷). Typical symptoms of PTS include combinations of the following: leg pain, limb swelling, sensations of leg heaviness, pulling, or fatigue (⁶), itching, cramps, and paresthesia (abnormal sensation) (⁷). Some of the signs of PTS include edema, redness, venous ectasia, hyperpigmentation, dependent cyanosis, skin thickening, eczema, white scar tissue (atrophie blanche), fibrosis of subcutaneous tissue (lipodematosclerosis), and ulcer(s) (⁸).

PTS is a frequent complication of DVT with development of PTS in approximately 20% to 50% of individuals within 2 years of diagnosis (⁷). PTS risk is higher with a proximal rather than a distal (i.e., calf) DVT as well as for older or obese individuals (⁶). Appropriate anticoagulation to prevent recurrent DVT is also a factor in preventing PTS (⁸). For those diagnosed with PTS, treatment typically includes use of elastic compressions stockings (ECS) to help with symptoms; compression devices may be used with more severe PTS (⁶).

Note that ECS may be used to reduce edema or venous hypertension, although not all studies have supported the value for prevention of PTS (⁷). Given the low risk (i.e., unlikely to cause harm), the use of ECS may be considered to help with limb swelling (⁶). A contraindication for the use of ECS includes symptomatic peripheral arterial disease because of worsening of claudication when wearing stockings (⁶). For those diagnosed with PTS, compression stockings can help with symptoms and improve daily function (⁶). As with any treatment, discussion with one's health care provider is recommended.

Exercise has been suggested to be of potential benefit in treating PTS, including leg strengthening and aerobic exercise (⁶). Other suggestions include avoiding sedentary time, elevating legs when possible (i.e., when sitting or lying down), avoiding prolonged exposure to the heat, and maintaining normal (nonobese) body weight (⁸).

RISK FACTORS

Factors that raise the risk of VTE include the following: experiencing a recent trauma, undergoing major surgery, being obese, having cancer, being pregnant, using hormone therapy, and smoking (¹). With age, risk increases (¹). Women have higher DVT incidence until around the age of 50 years when men have a greater risk (¹). Steroid hormones (especially estrogen) can increase the risk of developing a blood clot, thus increasing risk with use of oral contraceptives and hormone therapy (¹). With regard to ethnic background, African Americans have the highest risk, followed by Caucasians; Asian and Native Americans have the lowest risk (¹). Genetic factors also may increase risk (e.g., factor V Leiden and prothrombin G20210A mutations increase activity of coagulation factors; deficiencies in antithrombin III, protein C, and protein S decrease activity of antithrombotic pathways) (⁹). The interactions between risk factors and predispositions (acquired or inherited) make VTE a complex disease (⁵). Although approximately half of the cases occur for unknown reasons, about half have one or more risk factors as well as some sort of “triggering event” (e.g., trauma, surgery, immobilization) causing a clot, or clots, to form (¹).

Athletes may have additional factors to consider (⁹). Conditions identified for competitive athletes that may increase risk include contact-sport tissue trauma, dehydration leading to hemoconcentration, slower heart rate because of increased fitness resulting in circulatory stasis, and travel or injury giving rise to immobilization (¹⁰). Tips to lower risk related to travel are listed in Box 2. Hypercoagulability also may be related to strenuous exercise (e.g., increase in prothrombotic markers, activation of fibrinolytic system, and increased platelet aggregation) (¹⁰). The physical size of athletes may increase risk; even if not obese, being larger (i.e., taller, bigger legs) could impact blood flow and thus increase risk (³). For females, added risk factors include oral contraceptive use and pregnancy (¹⁰). Although not the focus of this article, DVT in the arm may occur for athletes such as baseball pitchers whose sport requires heavy use of the arms with related narrowing of the thoracic outlet (³).

BOX 2. Travel Tips

To lower the risk of clotting during travel, consider the following (^11,12):

• Get up and move
• ○ If traveling by plane, select an exit row or aisle seat to allow leg room to stretch and get up to walk if possible
• ○ If traveling by car, schedule stops to exit the vehicle to walk and stretch
• ○ While sitting, exercise calf muscles (e.g., raise and lower heels while keeping toes on the floor or raise and lower toes while keeping heels on the floor) and stretch the legs
• Avoid compression
• ○ Avoid tight clothes or braces that can compress leg veins
• ○ Avoid sitting with legs crossed
• ○ Avoid footrests that press on the calves
• Food and fluid
• ○ Hydrate — drink water and juices; limit caffeine and alcohol
• ○ Eat low fat — lower intake of triglycerides, which can activate platelets and clotting factors

For those at risk of DVT, consult with one’s doctor, considering (¹¹) the following:

• Properly fitted medical compression stockings to help minimize blood pooling (socks that have graduated compression with more pressure at the ankles with less pressure up the calf)
• Medication before travel to prevent clotting as prescribed and recommended by one’s doctor

TREATMENT

Individualization of treatment is key given the many considerations such as location (proximal vs. distal), genetic factors, and whether the cause is known or unknown, among others. Thus, a personalized plan should be developed in consultation with one’s health care provider. Anticoagulant drugs are commonly used within the therapy for VTE. For DVT involving proximal leg veins, anticoagulation is suggested (¹³); however, for distal (below-the-knee), the evidence for use of anticoagulation is less clear (¹⁴). In some cases, for below-the-knee DVT, surveillance with follow-up ultrasound is used (¹⁴). The role of anticoagulants is to slow the time it takes for blood to clot, therefore preventing new clots as well as preventing growth of existing clots (¹⁵). Anticoagulants do not dissolve clots, rather the body will dissolve the clot naturally (completely or partially) (¹⁵). Although beyond the scope of this article, risks and benefits of various medications must be considered on an individual basis; for more information, see Nutescu et al. (¹⁶) and Streiff et al. (¹⁷). For a patient guide, see Waldron and Moll (¹⁵).

In the past, early treatment of DVT included bed rest and anticoagulation; now, early mobilization with anticoagulation is typical. In general, light activity after a DVT has not been shown to increase the chance of developing a PE compared with those who are not active (¹⁸). Walking early on may provide benefits, including reducing the risk of the DVT extending, improving resolution of symptoms, and reducing long-term symptoms of PTS (^19,20).

PHYSICAL ACTIVITY AND EXERCISE

The safety of engaging in physical activity and exercise after a DVT is a question that many active individuals will have. Consulting with one’s physician is recommended to determine personalized plans related to activity or sport participation, given the many factors related to risk such as location of the DVT (proximal or distal) and genetic factors, as well as treatment choices (e.g., use of particular anticoagulants).

“The safety of engaging in physical activity and exercise after a DVT is a question that many active individuals will have. Consulting with one’s physician is recommended to determine personalized plans related to activity or sport participation, given the many factors related to risk such as location of the DVT (proximal or distal) and genetic factors, as well as treatment choices (e.g., use of particular anticoagulants).”

Although encouraging, research related to mobilization does not address questions related to a return to training. Return-to-play guidelines for athletes are limited (^9,10). Refraining from training for 3 weeks after a DVT has been suggested, with gradual progression into training (e.g., walking to jogging to running) over the following weeks while watching for a return of signs or symptoms (^9,20). A case study describing a triathlete's DVT treatment is in Box 3.

BOX 3. Case Study

Within a case study of a 25-year-old female triathlete who experienced a DVT in the calf, a return-to-training program included early mobilization after rest, elevation, and anticoagulation had reduced swelling and inflammation (⁴). The suggested program included 3 weeks of gradual return to activities of daily living to allow time for the clot to stabilize. The following 3 weeks included aerobic activities shifting from non–weight-bearing (swimming) to non–impact-loading (swimming and cycling) to impact-loading (running). This progression was based on animal studies in which endothelialization of a thrombus begins within 7 to 10 days and adhesion of the thrombus to the vessel wall occurs within 1 to 3 weeks; clot lysis and vein recanalization typically occur within 4 to 6 weeks. At any point, activity needed to be stopped if there was a return of signs or symptoms, and blood loss or bruising was to be reported. In actuality, the athlete accelerated the training program, starting to run during the 3 weeks after discharge from the hospital; this lead to leg swelling and pain, which impacted her training. She was on warfarin therapy for 3 months and also used an elastic compression sock to partially control the swelling. In a 2-year follow-up, the postexercise swelling was no longer an issue and her performance level was reported to be equal or better than before the DVT.

Additional factors must be considered for athletes in contact or collision sports; participation has not been recommended while on anticoagulation therapy (⁹). Use of intermittent dosing with newer medications (direct oral anticoagulants) has been proposed given the time to achieve peak activity and clearance (²¹). In other words, the medication would be suspended before competition to allow plasma concentrations to fall below the point where bleeding risk is increased and then at some point after competition medication could be resumed. This proposed management approach requires personalized pharmacokinetic/pharmacodynamic testing to determine and monitor plasma drug levels (²¹). More research is needed to determine the feasibility and safety of this proposed approach.

Thus, for individuals desiring to return to exercise or athletic competition, an individualized plan is needed. Balancing the desire to return to activity with safety is a challenge, and there is no “one size fits all” protocol. Research related to highly active individuals is needed to help clarify options. Recognizing risk factors and addressing those that can be modified is a step toward avoiding this potentially serious condition. In addition, recognizing signs and symptoms is key to avoid delays in seeking medical treatment. Helpful Internet resources are found in Box 4.

Box 4. Helpful Internet Resources

North American Thrombosis Forum: natfonline.org

Clot Connect: http://www.clotconnect.org

Centers for Disease Control and Prevention: https://www.cdc.gov/ncbddd/dvt/index.html

SUMMARY

Deep vein thrombosis occurs when there are clots in the deep veins of the body. Although about half of cases of DVT have symptoms (e.g., pain, swelling, discoloration, or redness in the affected area, along with warm skin), others have few symptoms. The need to individualize treatment is based on the complexity of the condition, including risk factors, known or unknown causes, and genetic factors. For active individuals, goals for treatment include addressing symptoms, avoiding clot extension or recurrence, and preventing PTS as well as a safe return to exercise and physical activity (⁴). This last aspect is unique from the general population and is an area with limited published guidelines.