section name header

Basics ⬇

Author(s): William M.Collins, DO and AlejandroCenturion, MD

Description

  • Venous thromboembolism (VTE) is a condition in which a blood clot (thrombus) forms in a vein.
  • When a thrombus occurs in the “deep veins” of the extremities or pelvis, it is called a deep vein thrombosis (DVT).
  • A thrombus in the lung is called a pulmonary embolism (PE).
  • A thrombus can limit blood flow through the vein, causing swelling and pain.
  • Most commonly, venous thrombosis occurs in the “deep veins” in the legs, thighs, or pelvis (DVT).
  • DVT can also occur in upper extremity veins (effort thrombosis).
  • In most cases, PE is caused by a DVT when part of a blood clot breaks off and lodges in the lung.

Epidemiology

Incidence

  • Estimated 900,000 affected in the United States yearly (1 to 2 per 1,000)
  • 60,000 to 100,000 die per year due to VTE.
  • Affects ~1 to 2 in 1,000 people every year
  • Rates increase with age and are higher in males compared to females.
  • There are no data on incidence of VTE in athletes.

Etiology and Pathophysiology

Virchow triad of venous stasis, vessel wall injury, and coagulation abnormality are considered the primary mechanisms for the development of venous thrombosis.

Genetics

Genetic defects such as factor V Leiden mutation or protein C or S deficiencies are associated with DVTs.

Risk-Factors

  • Older age
  • Active cancer
  • Antiphospholipid syndrome
  • Estrogen therapy
  • Pregnancy or peripartum
  • Personal or family history of VTE
  • Obesity
  • Autoimmune and chronic inflammatory diseases
  • Heparin-induced thrombocytopenia
  • Surgery
  • Trauma or fracture
  • Central venous catheter or pacemaker
  • Hospitalization
  • Nursing-home residence
  • Immobilization during travel (>4 hr)
  • Paresis or paralysis
  • Factor V Leiden
  • Prothrombin mutation
  • Antithrombin deficiency
  • Protein C deficiency
  • Protein S deficiency
  • Non-O blood group
  • It is postulated that athletes may be at increased risk of VTE due to long travel distances and direct trauma to tissues, although the claim is mostly supported by case studies and expert opinion (1).

General Prevention

  • Avoid prolonged immobility.
  • Hydrate adequately.
  • Consider compression stockings when immobilized.
  • Caution when using birth control; use low-estrogen pills when possible.
  • Prophylaxis for hospitalized patients

Commonly Associated Conditions

  • Malignancy accounts for 1/5 of all cases.
  • The list of risk factors is inclusive of associated conditions.

Diagnosis ⬆ ⬇

Wells criteria for DVT (1)[A]:

Active cancer within 6 mo+1
Paralysis or immobilization of lower extremity+1
Immobilization at least 3 days OR surgery in the previous 4 weeks<4 wk +1
Tenderness/cord along vein+1
Entire leg swollen+1
Calf circumference >3 cm vs. other leg+1
Alternative diagnosis likely−2
Interpretation
High probability+3
Moderate probability+1–2
Low probability0

Wells criteria for PE (1)[A]

Clinical signs and symptoms of DVT+3
PE no. 1 diagnosis or equally likely+3
Heart rate >100+1.5
Immobilization at least 3 days or surgery in the previous 4 wk+1.5
Previous, objectively diagnosed PE or DVT+1.5
Hemoptysis+1
Malignancy with treatment within 6 mo or palliative+1
Interpretation
High probability>6
Moderate probability+2–6
Low probability<2
  • A low or intermediate pretest probability of PE/DVT (Wells) with a negative D-dimer effectively rules out PE/DVT.
  • A high pretest probability with a negative D-dimer still warrants further evaluation with imaging.
  • A positive D-dimer warrants further imaging with computed tomography (CT) angiography or V/Q scan if CT not available.

History

  • Many patients are asymptomatic; however, the classic symptoms of DVT are swelling, pain, and discoloration in the involved extremity.
  • Clinical signs and symptoms of PE as the primary manifestations occur in 10% of patients with confirmed DVT.
  • Signs of PE are dyspnea, chest pain, cough, hemoptysis, and symptoms of DVT.

Physical Exam

  • Signs of DVT: Inspection of the extremity may reveal ipsilateral edema and erythema: >1- to 2-cm circumferential difference in leg.
  • Palpation of the extremity may reveal a palpable cord, increased warmth, and superficial venous dilation.
  • Homans sign: Passive dorsiflexion of the ankle elicits pain in the calf.
  • Phlegmasia cerulea dolens: reddish purple lower extremity from venous engorgement and obstruction
  • Signs of pulmonary embolus: tachycardia; tachypnea; low-grade fever; and abnormal electrocardiogram (ECG) S wave in lead I, Q wave in lead III, inverted T wave in lead III (S1Q3T3)

Differential Diagnosis

  • Superficial thrombophlebitis
  • Cellulitis
  • Torn muscles and ligaments
  • Ruptured Baker cyst
  • Bilateral edema (seen with heart, kidney, or liver disease) is rarely caused by DVT.
  • Prior DVT and postphlebitic syndrome
  • Arterial insufficiency
  • Arthritis
  • Lymphangitis
  • Extrinsic compression of iliac vein secondary to tumor, hematoma, or abscess
  • Hematoma
  • Lymphedema
  • Neurogenic pain
  • Prolonged immobilization or limb paralysis
  • Stress fractures or other bony lesions
  • Varicose veins

Diagnostic Tests & Interpretation

  • No blood test diagnoses or excludes DVT with complete certainty.
  • D-dimer (enzyme-linked immunosorbent assay [ELISA] technique) has sensitivities around 95% (2)[A].
  • Complete blood count (CBC) and prothrombin time (PT)/partial thromboplastin time (PTT) as baseline measurements
  • Labs for idiopathic DVT include factor V Leiden, prothrombin, serum homocysteine, factor VIII level, lupus anticoagulant, protein C and S levels, antithrombin activity, and anticardiolipin antibodies.
  • DVT: ultrasound (US) (gold standard) (2)[A]:
    • Sensitivities and specificities vary by vein with more accuracy in the proximal veins.
    • Sensitivities of 89–96%
    • Specificities of 94–99%
    • US is recommended for patients with high pretest probability (Wells criteria) in the lower extremities.
    • Duplex scanning (combination of color Doppler and B-mode US)
  • Venography is the historic gold standard:
    • Accurate but invasive
    • Associated with dye reactions
    • Can precipitate phlebitis
  • PE: CT angiography (gold standard) (1,3)[A]:
    • With intermediate to high risk, the positive predictive value is 92–96% (3)[A].
    • In high clinical risk, negative predictive value is 60% (3)[A].
  • Contraindication in those with kidney failure
  • V/Q scan if CT angiography not available

Treatment ⬆ ⬇

Outpatient treatment:

  • Anticoagulation (1,4,5)[A]
  • Factor Xa inhibitors or direct thrombin inhibitors (DTI) are considered treatment of choice (4)[A]:
    • Oral agents
    • Do not require laboratory monitoring
    • Excellent safety profile
  • Low-molecular-weight heparin (LMWH) is considered if DTI/factor Xa inhibitors are unavailable or cost prohibitive.
  • Warfarin is considered as last option given need for continuous monitoring of international normalized ratio (INR).
  • Contraindications:
    • Active internal bleeding
    • Uncontrolled hypertension (HTN)
    • Significant recent trauma or surgery
    • Central nervous system (CNS) tumor
  • Treatment duration (5)[A]:
    • Provoked DVT/PE: Recommend 3 mo of anticoagulation.
    • Unprovoked first time DVT/PE: Recommend 3 mo of anticoagulation and discussion of risk–benefit of indefinite anticoagulation at completion of 3 mo:
      • Low-or moderate-risk bleeding, recommend indefinite anticoagulation
      • High risk, recommend 3 mo of anticoagulation

Medication

  • Rivaroxaban 15 mg PO BID with food for 21 days, then 20 mg PO daily with food afterward (4,5)[A]
  • Apixaban 10 mg PO BID for 7 days, then 5 mg PO BID afterward
  • Dabigatran 150 mg PO BID
  • Enoxaparin: 1 mg/kg subcutaneous (SC) BID
  • Return to play (6)[C]:
    • Although anticoagulation remains the mainstay for DVT/VTE treatment, in recent decades there has been a shift from initial bed rest to early mobilization.
    • Athletes are encouraged to begin light ambulation within 24 hr of starting medical anticoagulation therapy (e.g., walking).
    • Weeks 1 to 3: reintroduction to activities of daily living
    • Week 4: begins engaging in non–weight-bearing activities (e.g., swimming)
    • Week 5: progresses to nonimpact-loading exercises (e.g., cycling)
    • Week 6: begins impact-loading exercises (e.g., running)
    • Week 6+: A gradual transition to sport-specific protocols as well as an increase in the duration and intensity of training may be initiated.
    • Progression through return-to-play protocol should be based on the athletes’ achievement and symptomatic improvement rather than based on a fixed timeline.
    • Athletes are not advised to participate in contact sports while on anticoagulation (6)[C].

Issues for Referral

Cardiology, pulmonary, hematology, or anticoagulation clinic is appropriate if the physician is uncomfortable with managing patients with DVT.

Ongoing Care ⬆ ⬇

Follow-up Recommendations

Patient Monitoring

No monitoring required for DTI or factor Xa inhibitors. INR levels should be evaluated frequently until stable with a target range between two and three (if using warfarin).

Patient Education

When patients are traveling, they should sit in seats that allow leg extension, take hourly walking breaks, wear loose clothing, and avoid crossing their legs.

Prognosis

PE will occur in 50% of untreated patients with DVT within days or weeks. If the DVT was caused by a thrombophilic disorder, the risk of repeat episode may be high.

Complications

Review all secondary disease or negative reactions that may occur during the course of an illness, that usually aggravate the illness, and any possible preventive measures. In addition, differentiate between acute/chronic, likelihood of complication, and common/rare.

Additional Reading ⬆ ⬇

  • Berkowitz JN, Moll S. Athletes and blood clots: individualized, intermittent anticoagulation management. J Thromb Haemost. 2017;15(6):1051–1054.
  • Bishop M, Astolfi M, Padegimas E, et al. Venous thromboembolism within professional American sport leagues. Orthop J Sports Med. 2017;5(12):2325967117745530. doi:10.1177/2325967117745530.

  • Centers for Disease Control and Prevention. Venous thromboembolism (blood clots). https://www.cdc.gov/ncbddd/dvt/data.html. Accessed September 24, 2018.

  • Eichner ER. Clots and consequences in athletes. Curr Sports Med Rep. 2014;13(5):287–288.
  • Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis. 2016;41(1):3–14.
  • Hirsh J, Hoak J. Management of deep vein thrombosis and pulmonary embolism. A statement for healthcare professionals. Council on Thrombosis (in consultation with the Council on Cardiovascular Radiology), American Heart Association. Circulation. 1996;93(12):2212–2245.
  • Hull CM, Harris JA. Cardiology patient page. Venous thromboembolism and marathon athletes. Circulation. 2013;128(25):e469–e471.
  • Mall NA, Van Thiel GS, Heard WM, et al. Paget-Schroetter syndrome: a review of effort thrombosis of the upper extremity from a sports medicine perspective. Sports Health. 2013;5(4):353–356.

References ⬆ ⬇

  1. Di Nisio M, Van Es N, Büller HR. Deep vein thrombosis and pulmonary embolism. Lancet. 2016;388(10063):3060–3073.
  2. Segal JB, Eng J, Tamariz LJ, et al. Review of the evidence on diagnosis of deep venous thrombosis and pulmonary embolism. Ann Fam Med. 2007;5(1):63–73.
  3. Wilbur J, Shian B. Diagnosis of deep venous thrombosis and pulmonary embolism. Am Fam Physician. 2012;86(10):913–919.
  4. Robertson L, Kesteven P, McCaslin JE. Oral direct thrombin inhibitors or oral factor Xa inhibitors for the treatment of deep vein thrombosis. Cochrane Database Syst Rev. 2015;(6):CD010956.
  5. Kearon C, Akl EA, Ornelas J, et al. Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report. Chest. 2016;149(2):315–352.
  6. Depenbrock PJ. Thromboembolic disorders: guidance for return-to-play. Curr Sports Med Rep. 2011;10(2):78–83.

Clinical Pearls ⬆

  • A DVT is associated with risk factors noted in Virchow triad of:
    • Venous stasis of an alteration in normal blood flow.
    • Vascular endothelial injury.
    • Hypercoagulability.
  • Essential workup includes a Doppler US (duplex scanning) of the affected extremity and CT angiography of chest if concerned for PE.
  • DTI or factor Xa inhibitors considered treatment of choice for outpatient management
  • Factor Xa inhibitors or DTI are considered treatment of choice for PE and DVT.
  • Athletes are not advised to participate in contact sports while on anticoagulation.