Pulmonary Venous Thromboembolism

Essentials of Diagnosis

• Predisposition to venous thrombosis, usually of the lower extremities

• Usually dyspnea, chest pain, hemoptysis, or syncope

• Tachypnea and a widened alveolar–arterial PO₂ difference

• Elevated rapid D-dimer and characteristic defects on CT pulmonary arteriography, ventilation-perfusion lung scan, or pulmonary angiogram

General Considerations

• Third most common cause of death in hospitalized patients

• Most cases are not recognized antemortem: < 10% with fatal emboli receive specific treatment

• Pulmonary thromboembolism (PE) and deep venous thrombosis (DVT) are manifestations of the same disease, with the same risk factors

  • Immobility (bed rest, stroke, obesity)

  • Hyperviscosity (polycythemia)

  • Increased central venous pressures (low cardiac output, pregnancy)

  • Vessel damage (prior DVT, orthopedic surgery, trauma)

  • Hypercoagulable states, either acquired or inherited

• Pulmonary thromboemboli most often originate in deep veins of the lower extremities

• PE develops in 50–60% of patients with proximal lower extremity DVT; 50% of these events are asymptomatic

• Hypoxemia results from vascular obstruction leading to dead space ventilation, right-to-left shunting, and decreased cardiac output

• Other types of pulmonary emboli

  • Fat embolism

  • Air embolism

  • Amniotic fluid embolism

  • Septic embolism (eg, endocarditis)

  • Tumor embolism (eg, renal cell carcinoma)

  • Foreign body embolism (eg, talc in injection drug use)

  • Parasite egg embolism (schistosomiasis)

Symptoms and Signs

• See Table 9–18

• Clinical findings depend on the size of the embolus and the patient's preexisting cardiopulmonary status

• Dyspnea occurs in 75–85% and chest pain in 65–75% of patients

• Tachypnea is the only sign reliably found in more than 50% of patients

• 97% of patients in the PIOPED study had at least one of the following

  • Dyspnea

  • Tachypnea

  • Chest pain with breathing

Differential Diagnosis

• Myocardial infarction

• Pneumonia

• Pericarditis

• Heart failure

• Pleuritis (pleurisy)

• Pneumothorax

• Pericardial tamponade

• Most North American centers use Wells' clinical prediction rule (Table 9–19) or something similar to guide a rapid D-dimer and CT-PA-based diagnostic algorithm.

• Concern over false positive D-dimer measurements in low-risk patients that prompt unnecessary CT-PA has led researchers to develop the Pulmonary Embolism Rule-Out Criteria (PERC, Table 9–20).

  • In a prospective analysis of 8138 ED patients at risk for PE, researchers identified 20% (1666) who had both a low (< 20%) pre-test probability of PE and met all 8 PERC criteria. This group had a 1.0% incidence of PE, with one fatality.

  • Patients with a Modified Wells Score ≤ 4 who meet all 8 PERC criteria do not need to undergo D-dimer testing and may be monitored clinically.

Laboratory Tests

• ECG is abnormal in 70% of patients

  • Sinus tachycardia and nonspecific ST-T changes are the most common findings

• Acute respiratory alkalosis, hypoxemia, and widened arterial–alveolar O₂ gradient (A–a DO₂), but these findings are not diagnostic (Table 9–18)

• Using a D-dimer threshold between 300 and 500 ng/mL (300 and 500 mcg/L), a rapid ELISA has shown a sensitivity for venous thromboembolism of 95–97% and a specificity of 45%

Imaging Studies

• Chest radiograph—most common findings

  • Atelectasis

  • Infiltrates

  • Pleural effusions

  • Westermark sign is focal oligemia with a prominent central pulmonary artery

  • Hampton hump is a pleural-based area of increased intensity from intraparenchymal hemorrhage

• Lung scanning (V/Q scan)

  • A normal scan can exclude PE

  • A high-probability scan is sufficient to make the diagnosis in most cases

  • Indeterminate scans are common and do not further refine clinical pretest probabilities

• Helical CT pulmonary angiography is supplanting V/Q scanning as the initial diagnostic study

  • It requires administration of intravenous radiocontrast dye but is otherwise noninvasive

  • It is very sensitive for the detection of thrombus in the proximal pulmonary arteries but less so in the segmental and subsegmental arteries

• Venous thrombosis studies

  • Venous ultrasonography is the test of choice in most centers

  • Diagnosing DVT establishes the need for treatment and may preclude invasive testing in patients in whom there is a high suspicion for PE

• In the setting of a nondiagnostic V/Q scan, negative serial DVT studies over 2 weeks predict a low risk (< 2%) of subsequent DVT over the next 6 weeks

• Pulmonary angiography is the historical reference standard for the diagnosis of PE

  • Invasive, but safe—minor complications in < 5%

  • Indicated when there is a high clinical probability and negative noninvasive studies

• MRI is a research tool for the diagnosis of PE

Medications

• See Table 14–16

• Full anticoagulation with heparin should begin with the diagnostic evaluation in patients with a moderate to high clinical likelihood of PE and no contraindications

• Once the diagnosis of proximal DVT or PE is established, it is critical to ensure adequate therapy

• LMWHs are as effective as unfractionated heparin

  • Administered in dosages determined by body weight once or twice daily without the need for coagulation monitoring

  • Subcutaneous administration appears to be as effective as the intravenous route

• Warfarin (vitamin K antagonist)

  • Initial dose: 2.5–10 mg/day

  • Usually requires 5–7 days to become therapeutic; therefore, heparin is generally continued for 5 days

  • Maintenance therapy usually requires 2–15 mg/day

  • Contraindicated in pregnancy; LMWHs are safe alternatives

  • Interacts with many drugs

• The 2016 CHEST Guideline and Expert Panel Report recommends direct oral anticoagulants (Factor Xa inhibitors and direct thrombin inhibitors) over warfarin (vitamin K antagonist) and LMWH in all patients with VTE without a cancer diagnosis and recommends LMWH for patients with cancer

• Guidelines for the duration of full anticoagulation

  • 3 months of anticoagulation after a first episode provoked by a surgery or a transient nonsurgical risk factor

  • Extended therapy (no scheduled stop date) for unprovoked or recurrent episode with a low to moderate risk of bleeding

  • Patients who continue to receive anticoagulation long-term should be reassessed for venous thrombosis at least annually

  • For patients with cancer, extended therapy with LMWH is recommended regardless of bleeding risk

• Thrombolytic therapy accelerates resolution of thrombi when compared with heparin, but does not improve mortality

  • Carries 10-fold greater risk of intracranial hemorrhage compared with heparin (0.2–2.1%)

  • Indicated in patients who are hemodynamically unstable while on heparin

• Venal caval interruption (IVC filters) may be indicated when a significant contraindication to anticoagulation exists or when recurrence occurs despite adequate anticoagulation

• IVC filters decrease the short-term incidence of PE, but increase the rate of recurrent DVT

Surgery

• Pulmonary embolectomy is an emergency procedure with a high mortality rate performed at few centers

Therapeutic Procedures

• Catheter devices that fragment and extract thrombus have been used on small numbers of patients

• Platelet counts should be monitored for the first 14 days of UFH due to the risk of immune-mediated thrombocytopenia

Complications

• Immune-mediated thrombocytopenia occurs in 3% of patients taking UFH

• Hemorrhage is the major complication of anticoagulation with heparin: risk of any hemorrhage is 0–7%; risk of fatal hemorrhage is 0–2%

• Risk of hemorrhage with warfarin therapy is 3–4% per patient year, but correlates with INR

• Chronic thromboembolic pulmonary hypertension occurs in about 1% of patients; selected patients may benefit from pulmonary endarterectomy

Prevention

• See Table 14–14

Prognosis

• Overall prognosis depends on the underlying disease rather than the thromboembolic event

• Death from recurrent PE occurs in only 3% of cases; 6 months of anticoagulation therapy reduces the risk of recurrent thrombosis and death by 80–90%

• Perfusion defects resolve in most survivors

When to Refer

• All patients evaluated for or diagnosed with a PE should be evaluated by an expert (typically a pulmonologist, hematologist, or internist)

When to Admit

• Patients with an acute PE should be admitted for stabilization, initiation of therapy, evaluation of cause of PE, and education