Aetiology

The coagulation system in blood is complex and highly regulated. Slight alterations in the systems that regulate coagulation can lead to bleeding or thrombosis.[7] The three factors that, individually or together, lead to most DVTs are vessel injury, venous stasis, and activation of the clotting system (known as Virchow's triad). Therefore, patients who develop DVT typically experience a trigger that leads to blood coagulation (e.g., surgery or trauma that activates the coagulation system), prolonged immobility that leads to stasis, or medications or illnesses (e.g., cancers, antiphospholipid syndrome) that can stimulate clotting.[8] Susceptibility to thrombosis is genetically mediated. Several genetic variants in the coagulation system itself (e.g., the factor V Leiden mutation) as well as outside the coagulation system (e.g., non-O blood type) increase the risk of thrombosis. All of these factors may interact, further increasing the risk of DVT.

There is a clear association between DVT and the following:

  • Active cancer

  • Recent major surgery (especially major orthopaedic procedures)

  • Recent hospitalisation

  • Recent trauma

  • Medical illness (especially diseases associated with inflammation, such as acute infection)

  • Hormone replacement and oral contraceptive oestrogen therapy.

Coronavirus disease 2019 (COVID-19), an infection caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with risk for VTE.[9] See our topic Coronavirus disease 2019 (COVID-19) for more information.

The presence or absence and timing of risk factors relative to the diagnosis of DVT has a major impact on determining the duration of anticoagulant therapy.[10] The International Society on Thrombosis and Haemostasis has published a 4-category system of classification (presented in order of increasing risk of recurrent venous thromboembolism after an initial episode), which is consistent with UK National Institute for Health and Care Excellence guidance:[11][12]

  • Major transient risk factors (e.g., major surgery; trauma; significant immobility (bedbound, unable to walk unaided, or likely to spend a substantial proportion of the day in bed or in a chair); pregnancy or puerperium; use of oral contraceptive/hormone replacement therapy), occurring within 3 months prior to thrombosis[12]

  • Minor transient risk factors (e.g., minor surgery), occurring within 2 months prior to thrombosis

  • Unprovoked (no pre-existing, major, transient provoking risk factor in the prior 3 months)[12]

  • Persistent risk factors (e.g., active cancer, autoimmune conditions such as systemic lupus erythematosus and inflammatory bowel disease).

The European Society of Cardiology guideline employs a similar framework, with some differences in terminology.[13]

Pathophysiology

Most blood clots that develop in the deep venous system of the leg begin to form just above and behind a venous valve.[14][15]

Clots often resolve spontaneously. When propagation of the thrombus does occur, it expands and grows proximally and across the lumen of the vein. A clot might occlude the entire lumen, but it is more commonly located on one peripheral aspect of the lumen. Even when the entire lumen appears to be occluded, a small amount of flow may continue on the extreme periphery of the clot. Many DVTs arise in the calf veins and propagate proximally. However, in some instances, such as during pregnancy or following total hip arthroplasty, the clot might form initially in the groin or iliac vein region.[15] These DVTs may propagate into the more distal veins. DVTs may arise in more than one separated venous segment at the same time.

Acute thrombus begins to be dissolved by the body's fibrinolytic system as soon as a clot begins to form. Thus, elevated levels of breakdown products of cross-linked fibrin, particularly the fragment called D-dimer, appear in the blood soon after a clot begins to form. Therefore, testing for D-dimer is an important component of the evidence-based approach to diagnosing suspected DVT.[16][17]

Classification

DVT: lower extremity

The following is an informal clinical classification.

(a) Superficial versus deep

  • Superficial vein thrombophlebitis (SVT; also known as superficial vein thrombosis). See our topic Superficial vein thrombophlebitis. 

    • Palpable thrombi in subcutaneous veins just below the skin (e.g., in a varicose vein) are classified as SVT; also referred to as superficial thrombophlebitis.

    • Most SVT confer less risk of complications than DVT and are managed differently. However, thrombi in the proximal portion of the greater saphenous vein (especially if within a few centimetres of the sapheno-femoral junction) may pose some risk of propagation and pulmonary embolisation because the greater saphenous vein joins the common femoral vein in the groin. SVT in the proximal greater saphenous vein are often managed in the same way as DVT.

  • Deep vein thrombosis

    • Thrombi form within veins deep to the muscular tissue planes.

(b) Proximal versus distal

  • Proximal venous thrombosis

    • DVTs in the popliteal or more proximal (femoral, deep femoral, common femoral, iliac, and vena cava) deep veins are classified as proximal.

  • Distal or calf vein thrombosis

    • DVTs in the three major axial calf veins (posterior tibial, anterior tibial, peroneal) below the popliteal vein and clots in the muscular vein branches (gastrocnemius and soleus) are considered distal deep calf vein thrombi. Some people may have anatomical variation of the distal deep veins, including paired peroneal veins, or a tibial-peroneal trunk rather than an immediate trifurcation distal to the popliteal vein. Thrombi in these areas are also distal DVTs. DVTs isolated to the distal veins have a lower risk of causing pulmonary embolism and post-thrombotic syndrome.

(c) Acute versus subacute, or chronic

  • Acute venous thrombosis confirmed by duplex ultrasound has the following characteristics: vein width at site of the thrombus is wider than the unaffected vein on the contralateral side (i.e., dilated vessel), and ultrasound echos are not prominent (i.e., the clot is not echogenic). Acute DVT often correlates with recent onset of symptoms. Acute clots may totally or partially obstruct flow.

  • Subacute or chronic DVTs are associated with some narrowing of the vein, partial but incomplete compressibility of the vessel, and hyperechogenicity in the vein lumen. The involved vein is normal-sized or contracted. Chronic clots may totally or partially obstruct flow. Chronic DVT can occur with or without anticoagulant treatment in symptomatic or asymptomatic DVT.

  • The time over which an acute DVT takes on subacute or chronic characteristics on ultrasound has not been well validated, and likely varies between people. Distinguishing a new acute DVT from a prior DVT is best accomplished by direct comparison with prior imaging studies.

DVT: upper extremity (not covered in this topic)

The following is an informal clinical classification.

(a) Superficial versus deep thrombosis

  • Thrombi in subcutaneous veins just below the skin that are palpable on the forearm or upper arm (i.e., basilic and cephalic veins) are classified as superficial.

  • Brachial, axillary, subclavian, or innominate (or brachiocephalic) veins, and the superior vena cava are classified as deep. The internal jugular vein is also considered to be a deep vein.

(b) Proximal versus distal

  • The distinction of proximal versus distal DVT is not clearly defined for the upper extremity. Management studies of upper extremity DVT have often included cases involving the axillary and more proximal veins. The risk of embolisation, and management of DVT in the brachial vein, is less certain.

(c) Acute versus subacute, or chronic

  • Criteria are similar to lower-extremity venous thrombosis. However, inability to compress the subclavian and other centrally located veins makes diagnosis and classification more difficult.

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