Relevance of the Problem

Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), remains one of the leading causes of morbidity and mortality among hospitalized patients, affecting approximately 7–11% of inpatients. Postoperative VTE is the second most common medical complication among more than 7 million patients discharged from 944 hospitals in North America. It is also the second leading cause of prolonged hospitalization and the third leading cause of increased mortality and healthcare costs.

Pulmonary embolism most commonly develops as a complication of deep vein thrombosis. More than 80% of confirmed PE cases are preceded by DVT, while over 50% of patients with proximal DVT subsequently develop PE. Every physician should therefore be familiar with the fundamental principles of diagnosing, preventing, and treating PE. Healthcare professionals should routinely assess each patient's risk of VTE, follow the latest evidence-based international guidelines for thromboprophylaxis, and initiate appropriate treatment when preventive measures fail.

Over the past 30 years, numerous randomized clinical trials have demonstrated that primary thromboprophylaxis is safe, effective, cost-efficient, and significantly reduces the incidence of both DVT and PE in hospitalized patients at increased risk of VTE. Current hospital guidelines recommend implementing formal VTE prevention protocols and incorporating them into institutional thromboprophylaxis policies. Pulmonary embolism is regarded as one of the most preventable causes of in-hospital death and is consistently identified as a top priority in patient safety initiatives.

Despite extensive clinical evidence and more than 20 clinical practice guidelines published since 1986, thromboprophylaxis remains underused or inadequately implemented in many countries. As a result, the incidence of VTE complications and PE-related mortality has not declined as expected. This highlights the persistent gap between evidence-based recommendations and their implementation in routine clinical practice.

This article reviews practical strategies for maintaining a high level of clinical suspicion for VTE, summarizes the most commonly used diagnostic approaches, and outlines current principles of prevention and initial treatment.

VTE Risk Assessment

According to studies conducted in the United States, DVT occurs in approximately 1.3% of hospitalized patients, while PE develops in about 0.4%. Overall, nearly 60% of all VTE events occur during hospitalization or shortly after discharge.

The major risk factors for VTE include:

• Surgery
• Acute medical illness requiring intensive care
• Cancer and anticancer treatment
• Trauma
• Prolonged immobilization
• Central venous catheterization
• Previous VTE
• Advanced age
• Obesity

Almost every hospitalized patient has at least one of these risk factors, and approximately 40% have three or more risk factors (Table 1).

Table 1. Causes of Reactive Thrombocytosis

Conditions That Increase the Risk of VTE

Conditions that predispose patients to venous thromboembolism (VTE) can be grouped into three broad categories that are easy to remember:

• Disorders affecting the balance between coagulation and fibrinolysis, such as cancer, hormone replacement therapy, pregnancy, and infection.
• Conditions that promote venous stasis, including immobilization for more than three days, advanced age (>65 years), surgery, and primary or secondary erythrocytosis.
• Conditions associated with increased platelet aggregation, such as hyperlipidemia, diabetes mellitus, and smoking.

VTE Diagnosis

The diagnostic approach to VTE can be divided into three stages:

• Clinical assessment and suspicion of PE.
• Tests that support suspicion of PE.
• Tests that confirm or exclude PE.

Clinical Assessment

The clinical presentation of pulmonary embolism is highly variable. However, unexplained respiratory symptoms such as dyspnea, chest pain, and tachypnea are among the most common manifestations.

Hospitalized patients are at particularly high risk of VTE and its complications. Advanced age, heart failure, previous VTE episodes, and other conditions requiring hospitalization further increase the likelihood of thrombosis. Acute illnesses such as myocardial infarction, acute decompensated heart failure, severe infection, or the need for emergency surgery are all independent VTE risk factors. These conditions also frequently result in prolonged immobilization, further increasing thrombotic risk.

Severe PE is often preceded by one or more smaller "warning" embolic events. When PE is suspected, the Wells clinical prediction rule is commonly used to estimate the patient's probability of PE. The Wells score has been validated for both hospitalized patients and those presenting to emergency departments (Table 2).

Table 2. Wells Score for Assessing the Probability of Pulmonary Embolism (PE)

Abbreviations: DVT – deep vein thrombosis; PE – pulmonary embolism; HR – heart rate.

It is important to emphasize that the Wells score should only be used in patients with suspected PE, not as a screening tool for all patients. It is most commonly used together with D-dimer testing. The Wells score does not establish the diagnosis of PE but helps determine the likelihood of disease and guide further diagnostic testing, particularly when PE is considered unlikely.

Tests That Support the Diagnosis of PE

Routine investigations—including chest radiography, electrocardiography (ECG), and arterial blood gas analysis (when respiratory failure is suspected)—cannot independently confirm or exclude PE. Although certain chest X-ray findings may raise suspicion, they are not diagnostic.

When a patient presents with dyspnea and chest pain, clinicians should first assess the probability of PE. Patients with a high clinical probability should undergo urgent confirmatory imaging while anticoagulant therapy is initiated without delay.

In contrast, D-dimer testing is particularly useful in patients with a low probability of PE. A negative D-dimer result obtained using a highly sensitive assay can safely exclude PE without the need for imaging studies.

D-dimers are degradation products of fibrin that are released into the circulation during thrombus breakdown, either through physiological fibrinolysis or following thrombolytic therapy. D-dimer testing is widely used to exclude low-risk PE and DVT. The test is inexpensive and may substantially reduce the need for computed tomography pulmonary angiography (CTPA), thereby decreasing patient exposure to ionizing radiation.

Compared with CTPA, ventilation-perfusion (V/Q) scanning, and magnetic resonance angiography, D-dimer testing is highly sensitive but relatively nonspecific, particularly in older adults (>65 years). Reported sensitivity ranges from 80% to 100%, whereas specificity ranges from only 23% to 63%.

A negative D-dimer result is therefore valuable for excluding PE in patients with a low clinical probability. However, a positive D-dimer result is not diagnostic and should always be followed by appropriate imaging studies.

Another useful investigation in suspected VTE is compression ultrasonography of the lower-limb veins. This examination is quick, non-invasive, suitable for immobilized patients and pregnant women, and has no contraindications or known adverse effects. However, its diagnostic accuracy depends greatly on the examiner's experience.

Compression ultrasonography has a reported sensitivity of approximately 90% and specificity of about 95% for detecting proximal lower-extremity DVT. Although approximately 90% of pulmonary emboli originate from deep leg vein thrombosis, proximal DVT is demonstrated in only 30–50% of patients with confirmed PE.

In clinical practice, evaluation of the femoral and popliteal veins using proximal and distal compression techniques is usually sufficient and has been validated in multiple clinical studies.

Tests That Confirm PE

Computed tomography pulmonary angiography (CTPA) remains the gold standard for confirming pulmonary embolism.

However, the 2016 CHEST guidelines recommend against performing CTPA in patients with a low clinical probability of PE and a negative high-sensitivity D-dimer test. Multiple studies have demonstrated that clinically significant PE can be safely excluded in such patients without further imaging.

Avoiding unnecessary CTPA reduces several potential risks. In addition to exposure to ionizing radiation, patients are exposed to iodinated contrast agents, which increase the risk of contrast-induced kidney injury and anaphylactic reactions.

Furthermore, CTPA performed in low-risk patients may detect clinically insignificant findings requiring unnecessary follow-up or identify isolated subsegmental pulmonary emboli, the clinical significance of which remains uncertain. Although many isolated subsegmental emboli may not require treatment, they are frequently managed with anticoagulants, unnecessarily increasing the patient's bleeding risk.

Population studies have shown that excessive use of CTPA has contributed to overdiagnosis and overtreatment of clinically insignificant PE, resulting in increased anticoagulant-related complications.

PE Treatment

The primary goal of treatment is to prevent further thrombus formation, limit thrombus extension, prevent recurrent embolic events, and allow the body's endogenous fibrinolytic system to dissolve existing clots.

When high-risk PE is suspected, stabilization of airway, breathing, and circulation is the first priority. Anticoagulation should be started immediately by administering intravenous unfractionated heparin at 80 IU/kg, followed by a continuous infusion of 18 IU/kg/hour. If subsequent investigations exclude PE, anticoagulant therapy should be discontinued.

Traditionally, treatment and secondary prevention of VTE have relied on heparin therapy followed by vitamin K antagonists (VKAs).

Today, direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, and dabigatran are increasingly used for PE treatment. Compared with traditional therapy, DOACs have fewer drug and food interactions, fixed dosing schedules, require no routine coagulation monitoring, and, unlike heparin, do not cause heparin-induced thrombocytopenia.

PE Prevention

Non-pharmacological measures

• Adequate hydration
• Elevation of the foot of the bed by 10–15°
• Graduated compression stockings or elastic bandages
• Intermittent pneumatic compression of the calves

Pharmacological prophylaxis

Commonly used medications include:

• Unfractionated heparin
• Low-molecular-weight heparins (LMWHs)
• Vitamin K antagonists
• Rivaroxaban (oral factor Xa inhibitor)
• Dabigatran (oral direct thrombin [factor IIa] inhibitor)
• Apixaban (oral factor Xa inhibitor)

Summary

Pulmonary embolism remains a major challenge in modern medicine. Sudden obstruction of the pulmonary arteries may cause acute, life-threatening but potentially reversible right ventricular failure. Diagnosing PE is often difficult, and some cases remain unrecognized.

Patients who survive PE remain at increased risk of developing chronic thromboembolic pulmonary hypertension, particularly if recurrent embolic events occur or pulmonary circulation fails to normalize.

Early recognition, timely diagnosis, and prompt initiation of appropriate treatment for both deep vein thrombosis and pulmonary embolism remain essential for improving patient outcomes.

Prepared by: Dr. Tadas Kaminsas

Source: Internistas, No. 1, 2017.