Bayer Pharma AG

Essence of this Article

Deep vein thrombosis (DVT) is usually the formation of a thrombus in the deep veins of the leg, although DVT may also occur in the veins of the upper limbs. DVT can occur spontaneously without a known underlying cause or after provoking events, such as trauma, surgery or acute illness. Complications of DVT include potentially life-threatening pulmonary embolism (PE), as well as post-thrombotic syndrome (PTS). DVT recurs with a relatively high frequency. The Wells’ score, a commonly used clinical score, quantifies the likelihood of an individual patient having DVT. Although a high Wells’ score indicates a clinical probability of DVT, an objective imaging technique, such as compression ultrasonography, must be used to confirm or rule out DVT.

Deep Vein Thrombosis

deep vein thrombosis leg

Major veins of the lower limb. The most common type of venous thromboembolism is deep vein thrombosis, which occurs most frequently in veins deep within the muscles of the leg and pelvis.

DVT is usually the formation of a thrombus in the deep veins of the leg, and may be referred to as proximal DVT or distal DVT. Occasionally, DVT also occurs in the veins of the upper extremities. DVT can occur spontaneously without known underlying cause (idiopathic thrombosis) or after provoking events, such as trauma, surgery or acute illness (provoked thrombosis).

The annual number of DVT events in the European Union (EU) is estimated at over 684,000,124 and in the United States (US) the rate of non-fatal symptomatic DVT events is estimated to be more than 376,000 per year.125

When patients taking part in clinical trials were routinely screened, the frequency of DVT without prophylaxis was approximately 10–40% in medical or general surgical patients and 40–60% in those who had major orthopaedic surgery.119

Complications of DVT include potentially life-threatening PE, in addition to post-thrombotic syndrome (PTS).126

Diagnosis of DVT

Signs and symptoms
Symptoms such as leg pain, tenderness, oedema or swelling are typically associated with DVT, but the condition may only be definitively diagnosed if validated objective diagnostic tests, such as compression ultrasonography, venography or magnetic resonance imaging (MRI) are performed.127

Clinical probability scores
One of the commonly used clinical scores for evaluating the probability of DVT was developed by Wells’ and colleagues. This tool quantifies the likelihood of an individual patient having DVT based on their medical history and physical examination. Therefore, clinical judgment plays a critical role in DVT diagnosis, because certain risk factors and markers of DVT can be assessed early in the diagnosis process.128

Wells’ score for prediction of DVT.128 A high score is 3 or more, a moderate score 1−2 and a low score 0

Parameter Score
Active cancer (treatment ongoing or within previous 6 months or palliative) 1
Paralysis, paresis or recent plaster immobilization of lower extremities 1
Recently bedridden for more than 3 days or major surgery within 4 weeks 1
Localised tenderness along distribution of the deep vein system 1
Entire leg swollen 1
Calf swelling by more than 3 cm when compared with asymptomatic leg 1
Pitting oedema 1
Collateral superficial veins 1
Alternative diagnosis as likely or greater than that of DVT –2
DVT, deep vein thrombosis.


Although a high Wells’ score indicates a clinical probability of DVT, an objective imaging technique such as compression ultrasonography, computed tomography (CT) venography or MRI must be used to confirm or rule out DVT. D-dimer testing can also be used to rule out DVT.

Compression ultrasonography
Compression ultrasonography (also called venous ultrasonography or ultrasound) is the most widely used method for evaluating suspected DVT.129 This safe, non-invasive test involves compressing and imaging the femoral veins down to the most proximal calf veins.130 Despite some limitations (e.g. operator dependence, lack of sensitivity in patients with oedema or significant obesity, inability to distinguish between an old thrombus and a fresh thrombus), ultrasonography is considered acceptable when combined with a probability score based on clinical variables.

venous ultrasonography - evaluating suspected DVT

Cross-sectional view of the popliteal by compression ultrasonography vein showing partial obstruction of the vessel lumen. This imaging technique renders the thrombus (no flow) as black, while areas of blood flow are coloured.

Computed tomography venography
CT venography detects both distal and proximal DVT. However, it is invasive, painful and expensive. For this reason, this diagnostic test is usually reserved for situations when clinical suspicion of DVT is not supported by compression ultrasonography findings. A related diagnostic test option, indirect CT venography, can be done at the same time as CT pulmonary angiography, with similar sensitivity and specificity to ultrasound.131

Magnetic resonance imaging
MRI employs a powerful magnetic field to generate a high-resolution image of anatomic structures. This non-invasive study may be used to diagnose DVT in patients when ultrasound examination is inappropriate or not feasible. Unlike CT venography, MRI does not involve radiation exposure but its use can be limited by a long examination time and a lack of access to equipment.132

D-dimer measurements
D-dimer is a protein fragment produced by thrombus degradation that is formed when plasmin dissolves the fibrin strands that hold a thrombus together.133 D­dimer blood tests vary in their accuracy. None is specific for VTE, but some have high sensitivity.133 However, a highly sensitive D-dimer test has high negative predictive value (i.e. if the results are negative, VTE is unlikely).134

Risk factors for recurrence

In addition to the high risk of PE and long-term complications, DVT is associated with a cumulative risk of VTE recurrence of approximately 21% within 5 years of the initial event.135 The risk of VTE recurrence appears greater if the initial event was unprovoked, or associated with persistent risk factors such as cancer rather than a transient risk factor like surgery.135-137

Three important risk factors were identified and quantified in the Vienna Prediction Model:138

  • Initial proximal (rather than distal) DVT
  • Male gender
  • Elevated D-dimer concentration

Short-term (rather than long-term) duration of anticoagulation therapy is also associated with recurrence.135

Patients with a previous history of VTE, malignancy or a haematological abnormality that predisposes them to thrombus formation (e.g. thrombophilia) are also at high risk of recurrent VTE. Homozygous Factor V Leiden or heterozygous Factor V Leiden and the prothrombin G20210A mutation are examples of the types of haematological abnormalities that confer a heightened risk of VTE recurrence.139

Measurement of specific proteins involved in coagulation can help guide clinical decision-making, although this type of laboratory assessment is rarely done in clinical practice. For example, a high level of coagulation Factors VIII, IX and XI signals an increased risk of VTE recurrence.140 In addition, a D-dimer concentration above 250 ng/ml measured 3 weeks after discontinuation of anticoagulation is associated with a 3.1-fold increased risk of VTE recurrence at 2 years.141

Elevated P-selectin levels are also associated with VTE recurrence within the first year after an initial event.142 A high plasma level of soluble P-selectin (sP-selectin) is modulated by variations of the P-selectin gene and is a predictive biomarker for VTE recurrence in patients with a first episode of unprovoked VTE. However, the clinical applicability of P­selectin needs further investigation.143

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