Venous Thromboembolism: Diagnosis and Treatment

Tachypnea (≥20/min)

54 %

Dyspnea (at rest or on exertion)

73 %

Tachycardia (>100/min)

24 %


28 %

Rales (crackles)

18 %


34 %

Decreased breath sounds

17 %

Pleuritic pain

44 %

Increased P2

15 %

Leg pain

44 %

Jugular venous distension

14 %

Swelling in the lower limbs

41 %

Wheezes or Rhonchi

4 %


21 %

Adapted from: “Stein PD, Beemath A, Matta F, Weg JG, Yusen RD, Hales CA, et al. Clinical characteristics of patients with acute pulmonary embolism: data from PIOPED II. Am J Med. 2007;120(10):871–9”


Deep Vein Thrombosis Diagnosis

The clinical manifestation of deep vein thrombosis of the lower limbs varies widely and is often asymptomatic. The preclinical test developed by Wells and colleagues is a clinical model to predict the probability of deep vein thrombosis. Therefore, the Wells scale is the most widely used scale for symptomatic patients with this suspicion of venous thrombosis. The risk increases as the risk factors increase. This statement is the basis for stratifying patients by combining the number of risk factors with clinical signs and symptoms. A score based on eight Wells criteria is a consistent and repeatable tool for stratifying outpatients as having a high, moderate, or low probability of presenting with deep vein thrombosis (Table 12.2) [9].

Table 12.2
Clinical model for determining the probability of having deep vein thrombosis , as proposed by Wells et al. [10]

Clinical feature


Active cancer


Paresis, paralysis, or immobilization of the lower limbs


Immobilization (>3 days) or major surgery (up to 4 weeks)


Pain or discomfort along the deep venous veins trajectory


Limb edema


Calf swelling (>3 cm) compared to the normal leg


Cacifo’s sign in the affected limb (unilateral)


Visible superficial collateral veins


Previously documented deep vein thrombosis


A more likely differential diagnosis from another condition


Reprinted with permission from: “Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350(9094):1795–8”

The score of all of the clinical features presented by a patient must be summed and applied in the following table to establish the classification risk (Table 12.3).

Table 12.3
Group of risk for deep vein thrombosis according to the score of the Wells preclinical testing [10]


Deep vein thrombosis probability


0 points

3 % (95 % IC; 1.7–5.9 %)

Low risk

1 or 2 points

17 % (95 % IC; 12–23 %)

Moderate risk

3 or more points

75 % (95 % IC; 63–84 %)

High risk

Reprinted with permission from: “Wells PS, Anderson DR, Bormanis J, Guy F, Mitchell M, Gray L, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet. 1997;350(9094):1795–8”

As the clinical manifestation of deep vein thrombosis is highly variable and the first clinical manifestation can be a fatal pulmonary embolism, clinical diagnosis has a low sensitivity. Thus, despite of rating deep vein thrombosis risk by the application of Wells preclinical testing, objective diagnostic methods are essential to a correct diagnosis [11].

Additional Tests That Increase Accuracy for the Diagnosis of Deep Vein Thrombosis

Serum D-dimer : Plasma D-dimer is a product of fibrin degradation and its plasma concentration is high in cases of acute venous thromboembolism. Testing for D-dimer levels has a sensitivity of 60–97 % for the diagnosis of deep vein thrombosis, but the specificity is lower than 35 % [4]. Thus, in isolation, this test is not a suitable method for diagnosing acute venous thrombosis, as there are many other medical conditions that also increase levels of D-dimer: recent surgical procedures, sepsis, hemorrhage, trauma, cancer, old age, pregnancy, and long periods of hospitalization. However, a negative result, i.e., low concentrations of D-dimer, associated with preclinical low probability (low-risk patient) may exclude the diagnosis of deep vein thrombosis, once some studies have shown that it is safe not to treat these patients because the deep vein thrombosis incidence in 3-month follow-up is too low [9, 12, 13].

Venography: Venography is an invasive method that was considered the gold standard for the diagnosis of deep vein thrombosis. It now has been replaced by the vascular Doppler ultrasound . Venography is a high-cost method that exposes the patient to ionizing radiation and to injection of iodinated contrast middle. The latter can cause allergy, vein thrombosis, and nephrotoxicity [14]. However, venography is still reserved in cases in which the diagnosis of deep vein thrombosis remains inconclusive and during endovascular interventions [14, 15].

Vascular ultrasound ( duplex scanning ) : This technique replaced venography and is considered the main imaging method for the diagnosis of deep vein thrombosis. Duplex scan is a validated technique due to its high sensitivity and specificity [16, 17]. Vascular ultrasound is noninvasive, radiation-free, cost-effective, and available at most institutions [16, 17]. Thus, vascular Doppler is the method of choice for the initial investigation of deep vein thrombosis, although diagnosis using this method may be examiner-dependent [18, 19].

Computed tomography (CT) : CT is an excellent method for the diagnosis of pulmonary embolism. However, it has a lower accuracy for the diagnosis of deep vein thrombosis. Peterson et al. demonstrated that, although the sensitivity of CT is 93 %, with a negative predictive value of 97 %, CT’s ability to accurately diagnose deep vein thrombosis has a specificity of 71 % with a positive predictive value of only 53 % [20]. CT has not been well studied for the diagnosis of acute deep vein thrombosis of the calf veins, which implies that the role of this technique as a comprehensive diagnostic modality for the lower limbs is questionable.

Magnetic resonance imaging : Magnetic resonance venography is an alternative method for the diagnosis of deep vein thrombosis. In a meta-analysis performed by Sampson et al. [21], it was found that the sensitivity was 91.5 % and the specificity was 94.8 %. However, estimates of both sensitivity and specificity were subject to significant heterogeneity. The studies for the diagnosis of acute venous thrombosis show good results for proximal venous segments, but decreased sensitivity to distal veins [21]. In the study of femoral vein thrombosis, magnetic resonance imaging showed 100 % sensitivity and 97 % specificity. The overall sensitivity for lower limb thrombus detection is 87 % and a specificity of 98 % [22].

In 27 % of patients with pulmonary embolism, the magnetic resonance imaging identified the thrombus source, which was not previously identified by vascular ultrasound [23]. Therefore, magnetic resonance venography may be an alternative method for patients in whom vascular ultrasound is not suitable, feasible, or inconclusive.

Strategies for the Diagnosis of Deep Vein Thrombosis in Specific Clinical Situations

Based on the specific clinical situation of each patient, practitioners can use different strategies for the diagnosis of deep vein thrombosis:

  1. 1.

    Outpatients: Nonhospitalized patient with suspected deep vein thrombosis should have three steps for the diagnostic approach including:

    1. (a)

      Risk stratification using the Wells criteria (preclinical testing)


    2. (b)

      Serum levels of D-dimer


    3. (c)

      Use of an imaging method (duplex scanning preferably)


    The negative predictive value for venous thrombosis approximates to 100 % in outpatients who are considered to be low risk based on the Wells criteria in association with a negative D-dimer test . Similar results were shown in intermediate-risk patients who also had a negative D-dimer result. For these outpatients, no further testing is necessary to exclude the diagnosis of deep vein thrombosis [24, 25]. In contrast, a high probability of deep vein thrombosis in outpatients may require immediate anticoagulation with no additional test, pending the completion of vascular ultrasound [26, 27]. Anticoagulation treatment should be maintained until the diagnosis is confirmed or not by vascular ultrasound. If the result of the ultrasound is negative, the practitioner should measure D-dimer levels as a negative value excludes the diagnosis. In cases of a positive D-dimer result, vascular ultrasound should be repeated in 3–7 days.

    Therefore, in nonhospitalized patients, the combination of a low clinical probability associated with a negative D-dimer result is sufficient to exclude deep vein thrombosis. A positive D-dimer result in patients who are considered to be moderate or high risk is an indication for immediate anticoagulation therapy. A vascular ultrasound could be scheduled for the next available agenda [26, 28].


  2. 2.

    Hospitalized patients (surgical or clinical): The sensitivity and specificity of the D-dimer test are substantially lower in hospitalized patients, even in those classified as low risk [29]. Several factors associated with such patients determine an elevated serum level of D-dimer [29]. Therefore, the diagnosis of a clinically suspected deep vein thrombosis in a hospitalized patient requires confirmation by imaging methods, particularly vascular ultrasound [29].


  3. 3.

    Pregnancy: The diagnosis of deep vein thrombosis in pregnant women has peculiarities. D-dimer levels are not as useful parameters once these levels are elevated during pregnancy. For such reasons, vascular ultrasound is the best method of diagnosis [30]. The anticoagulation approach should also be considered carefully due to the risk of bleeding complications.


Pulmonary Embolism

The diagnosis of pulmonary embolism is based on clinical manifestations and objective diagnostic methods.

Thorax X-ray —This test is often normal at the initial presentation. Faint infiltration can be observed, along with reduced lung parenchyma and elevation of the hemidiaphragm [31].

Electrocardiogram —The most frequent finding is tachycardia. Other changes in the electrocardiogram that indicate a diagnosis of pulmonary embolism include characteristic findings in S1, Q3, and T3 [31].

AngioCT —CT angiography allows the professional to visualize the thrombus within the vessels and to identify changes in the vascular lumen and lesions in the lung parenchyma (infarcts, atelectasis, and nodules). This test has high sensitivity and specificity [32] (Fig. 12.1).


Fig. 12.1
Photograph of chest CT angiography with 3D reconstruction. Observe the rich pulmonary vasculature. The center corresponds to the main pulmonary artery alongside the aorta

Pulmonary angiography —Although invasive, pulmonary angiography is considered the gold standard for the diagnosis of pulmonary embolism. The indications for this method include patients using thrombolytic medications or candidates for embolectomy (mechanical removal of the embolus) (Fig. 12.2).


Fig. 12.2
Pulmonary angiography of the left pulmonary artery. Note the good vascularization in the upper half of the left lung. In contrast, note the poor perfusion of the lower half of the lung, where segmental and subsegmental blockage is apparent. Further note the high caliber of this pulmonary artery (pulmonary hypertension)


The general objective of the treatment of deep vein thrombosis is to prevent progression of the thrombus, to reduce morbidity (pain and swelling), and reduce mortality associated with pulmonary embolism. Treatment also aims to avoid recurrence of thromboembolic events and to decrease complications related to the post-thrombotic syndrome and pulmonary hypertension [33, 34].

Clinical recommendations: Consist of recommendation for early ambulation, as this approach reduces edema and discomfort associated with the use of elastic stockings, even in the presence of a floating thrombus [30, 35].

Compression Therapy

The pathophysiology of the post-thrombotic venous disease is characterized by venous hypertension associated with valvular incompetence or luminal obstruction. As a result, venous stasis occurs in the affected leg [36, 37]. Compression therapy can be achieved through elastic stockings or nonelastic dressings. Brandjes et al. reported that the use of compression stockings with 30–40 mmHg for at least 2 years reduced the incidence of post-thrombotic syndrome by 50 % [38]. Prandoni et al. found similar results in patients with proximal vein thrombosis [4]. Partsch et al. showed that ambulation and elastic leg compression decreased pain and edema in comparison to patients at rest [37].

Pharmacological treatment: The conventional approach for the treatment of venous thromboembolism in patients with a confirmed or strongly suspected diagnosis of deep venous thrombosis is the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH) during 5–7 days followed by the oral Vitamin K antagonists (e.g., warfarin , acenocumarol) [30].

Initial treatment should start with low molecular weight heparin, unfractionated heparin, or fondaparinux for 5–7 days and suspended when the International Normalization Ratio (INR) reaches 2.0–3.0. Low molecular weight heparin has traditionally been the best choice. Warfarin should be started on the first day of treatment and continued with control based on the INR. The patients should then have anticoagulant therapy for a minimum of 3 months [30]. This combined approach is necessary once the sole use of oral vitamin K antagonists in the first days after the oral intake leads to a hypercoagulable state. Such situation could increase the extent of the thrombus and thereby lead to pulmonary embolism. Vitamin K antagonists tend to reduce the production of proteins C and S in the first 2–4 days, which are natural anticoagulants. Only after this time there is the decrease of the production of procoagulant factors II, VII, IX, and X [39]. The updated “Chest Guidelines” recommends low molecular weight heparin over vitamin K antagonists as the treatment of option for patients with venous thromboembolism and cancer. It also suggests non-vitamin K antagonist oral anticoagulants over vitamin K antagonists for initial and long-term anticoagulant therapy for patients with venous thromboembolism and no cancer [40].

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Sep 30, 2017 | Posted by in CARDIOLOGY | Comments Off on Venous Thromboembolism: Diagnosis and Treatment
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