Venous thromboembolism (VTE)

Deep venous thrombosis (DVT) and pulmonary

embolism (PE) can be considered under this heading.
The majority (79%) of pulmonary emboli arise from
the propagation of lower limb DVT. Rare causes include
septic emboli (from endocarditis affecting the tricuspid
or pulmonary valves), tumour (especially choriocarcinoma),
fat, air, amniotic fluid and placenta.
The incidence of VTE in the community is unknown;
it occurs in approximately 1% of all patients admitted
to hospital and accounts for around 5% of in-hospital
deaths.
It is a common mode of death in patients with
cancer, stroke and pregnancy.
 Clinical Features
VTE can be difficult to diagnose. It may be helpful to
consider the following:
• Is the clinical presentation consistent with PE?
• Does the patient have risk factors for PE?
• Are there any alternative diagnoses that can explain
the patient’s presentation?
Presentation varies depending on the number, size and
distribution of emboli, and the underlying cardiorespiratory
reserve. A recognised risk factor is present in between 80% and 90% of
Patients .
The presence of one or more risk factors may
multiply the risk.
 Investigations
Chest radiography
The chest X-ray is most useful in excluding key differential diagnoses,
e.g. pneumonia or pneumothorax. Normal appearances in an acutely
breathless and hypoxaemic patient should raise the suspicion of PE, as
should bilateral changes in a patient presenting with unilateral pleuritic
chest pain.
Electrocardiography
The ECG is often normal but is useful in excluding other important
differential diagnoses such as acute myocardial infarction and
pericarditis.
The most common abnormalities in PE include sinus
tachycardia and anterior T-wave inversion but are nonspecific; larger
emboli may cause right heart strain revealed by an S1Q3T3 pattern, ST-
segment and T-wave changes, or the appearance of right bundle
branch block.
Arterial blood gases
Arterial blood gases typically show a reduced PaO2, a normal or low
PaCO2 and an increased alveolar–arterial oxygen gradient, but may be
normal in a significant minority.
A metabolic acidosis may be seen in acute massive PE with
cardiovascular collapse.
D-dimer and other circulating markers
D-dimer is a specific degradation product released into the circulation
when cross-linked fibrin undergoes endogenous fibrinolysis.
An elevated D-dimer is of limited value, as it occurs in a number of conditions
including PE, myocardial infarction, pneumonia and sepsis.
However, low D-dimer levels (< 500 ng/mL measured by ELISA), particularly
where clinical risk is low, have a high negative predictive value and further
investigation is unnecessary.
The D-dimer result should be disregarded in high-risk patients, as further
investigation is mandatory even if it is normal. Other circulating markers that
reflect right ventricular micro-infarction, such as troponin I and brain
natriuretic peptide, are under investigation.
Imaging
A range of imaging techniques can be used to confirm suspected PE.
The choice depends on the clinical probability of VTE, the condition of
the patient, local availability, risks from iodinated contrast medium,
radiation exposure and the associated costs.
CT pulmonary angiography (CTPA) is the most commonly sought first-
line diagnostic test.
It has the advantage of visualising the distribution and extent of the
emboli, or highlighting alternative diagnoses such as consolidation,
pneumothorax or aortic dissection.
The sensitivity of CT may be increased by simultaneous visualisation
of the femoral and popliteal veins.
Ventilation–perfusion scanning is less commonly used, as its utility is
limited in patients with pre-existing chronic cardiopulmonary pathology
and the scan is most frequently regarded as indeterminate.
It is most useful in patients without significant cardiopulmonary
disease and a normal chest X-ray; interpretation should be informed by
clinical probability.
Colour Doppler ultrasound of the leg veins remains the investigation of
choice in patients with suspected DVT, but may also be applied to
patients in whom PE is suspected, particularly if there are clinical signs
in a limb, as many will have identifiable proximal thrombus in the leg
veins.
Echocardiography
Bedside echocardiography is extremely helpful in the differential
diagnosis and assessment of acute circulatory collapse .
Acute dilatation of the right heart is usually present in massive PE, and
thrombus (embolism in transit) may be visible.
Pulmonary angiography
Conventional pulmonary angiography has been largely superseded by
CTPA but may still be used in selected settings or for delivering catheter-
based therapies.
Management
General measures
Prompt recognition and treatment are potentially life-saving.
Oxygen should be given to all hypoxaemic patients at a concentration necessary to
maintain arterial oxygen saturation above 90%.
Circulatory shock should be treated with intravenous fluids or plasma expander, but
inotropic agents are of limited value, as the hypoxic dilated right ventricle is near
maximally stimulated by endogenous catecholamines.
Diuretics and vasodilators should also be avoided, as they will reduce cardiac output.
Opiates may be necessary to relieve pain and distress but should be used with
caution
in the hypotensive patient.
Resuscitation by external cardiac massage may be successful in the moribund
patient by dislodging and breaking up a large central embolus.
Anticoagulation
Anticoagulation should be commenced immediately in patients with a
high or intermediate probability, but maybe safely withheld in patients
with low clinical probability pending investigation.
Heparin reduces further propagation of clot, the risk of further emboli,
and lowers mortality.
It is most easily administered as subcutaneous low molecular weight
heparin. The dose is based on the patient’s weight and there is usually
no requirement to monitor tests of coagulation.
The duration of LMWH treatment should be at least 5 days, during
which time oral warfarin is commenced.
LMWH should not be discontinued until the international normalised
ratio (INR) is greater than 2.
Patients with a persistent prothrombotic risk ora history of previous
emboli should be anticoagulated for life, whereas those with an
identifiable and reversible risk factor usually require only 3 months of
If the condition is idiopathic or risk factorsare weak, anticoagulation for 6
months is recommended, although the appropriate duration is unclear.
Long-term, low-intensity warfarin therapy (target INR 1.5–2.0) appears to be
associated with reduced risk of bleeding and may prevent recurrent
thromboembolism.
The role of D-dimer and right heart function in decision-making on duration of
anticoagulation is currently being examined.
Thrombolytic therapy
Thrombolysis is indicated in any patient presenting with acute massive PE
accompanied by cardiogenic shock.
In the absence of shock, the benefits are less clear but it may be considered in
patients presenting with right ventricular dilatation and hypokinesis or severe
hypoxaemia.
Patients must be screened carefully for haemorrhagic risk, as there is a high
risk of intracranial haemorrhage.
Surgical pulmonary embolectomy may be considered in selected patients but
carries a high mortality risk.
Caval filters
A patient in whom anticoagulation is contraindicated, who has suffered
massive haemorrhage on anticoagulation, or recurrent VTE despite
anticoagulation, should be considered for an inferior vena caval filter.
The introduction of retrievable caval filters has been useful in
patients with temporary risk factors.
Prognosis
Patients who have suffered symptomatic VTE carry an increased risk of
further events, particularly if a persisting risk factor is present.
The risk of recurrence is highest in the first 6–12 months after the initial
event, and by follow-up at 10 years just under one-third of patients
may have suffered a further event.
Risks of recurrent VTE are lowest in those with temporary or reversible
risk factors. The immediate mortality is greatest in those with
echocardiographic evidence of right ventricular dysfunction or cardiogenic
shock. The vast majority of patients attain normal right heart function by 3
Weeks but persisting pulmonary hypertension may be present in around 4% of
patients by 2 years. A minority progress to overt right ventricular failure.