INTRODUCTION

Pulmonary embolism (PE) is the third most common cause of cardiovascular death after acute
myocardial infarction and stroke. As well as leading to PE, deep vein thrombosis (DVT) frequently results
in the post-thrombotic syndrome, which is a major cause of long-term disability (see p. 1010). Venous
thromboembolism (VTE, the term describing both conditions), is multicausal, often arising as a result of
transient provoking factors, or in individuals with a heritable or acquired predisposition, but in up to
50% of people no cause can be established.

The clinician must be very familiar with VTE because:

• it is common, particularly in those admitted to hospital or those who have had surgery,
suffered trauma or have other causes of reduced mobility

• it is life-threatening

• it is preventable: PE is the most common avoidable cause of death in patients admitted

to hospital, and the single leading direct cause of death during pregnancy and the puerperium in the UK

• it can be difficult to diagnose: the clinical features and routine initial investigations,
particularly for PE, are often non-specific, and this leads to diagnostic delays with potentially serious
consequences

• its treatment can be hazardous: anticoagulant therapy, which may be long-term, is

effective but carries the risk of major, even fatal, bleeding, and can be particularly challenging in patients
with co-morbidities

PATHOGENESIS OF THROMBOSIS
Thrombosis is the pathological process by which a localized solid mass of blood constituents (a blood
clot or thrombus) forms within a blood vessel, mostly as a result of fibrin formation with a variable
contribution from platelets and other cells.

This differentiates it from physiological hemostasis, the process in which a fibrin-rich blood clot occurs
outside the vessel-wall lining (or endothelium) as a result of injury. Thrombi form on, and are attached
to, the vessel wall but fragments (emboli) may break off and occlude vessels downstream.

• Thrombosis can occur in both arteries and veins (for example, the usual cause of myocardial
infarction is thrombosis within a coronary artery).

• The pathogenesis of thrombosis in these two sites is different, reflecting the different shear
stresses in arteries and veins, and the contribution that rupture of atheromatous plaques makes
to the initiation of arterial thrombosis.
 • Arterial clots are described as white thrombi and venous clots as red thrombi, reflecting the
contribution that platelets, as well as fibrin, make to the former, and fibrin and red cells to the
latter.

• Thrombosis is thought to be the cause of about 25% of all deaths worldwide each year.

Terms
Most often, venous thrombosis originates in the deep veins of the leg: hence the term deep vein
thrombosis. It is thought that the process starts within the pocket of one of the valves that line the
veins, where flow may be turbulent and localized hypoxia may develop, resulting in endothelial
dysfunction. The thrombus may remain localized to the leg veins or may embolize through the
circulation to result in a pulmonary embolus. A minority (about 10%) of episodes of venous thrombosis
arise in other sites, such as the upper limb, the cerebral venous sinuses and the splanchnic veins
(hepatic, portal and mesenteric veins). Apart from upper limb venous thrombosis, these unusual-site
thromboses are described further in relevant specialty-specific chapters.

If confined to the calf veins, the thrombus is called a calf or distal DVT. Untreated, the thrombus may
extend proximally and, when it reaches the popliteal vein or above, is called a proximal DVT.

Thrombi at this level are larger, and more likely to embolize and be transported with blood flow through
the large veins of the pelvis and abdomen to the right atrium and ventricle. From there, they are
pumped into the pulmonary arteries, which progressively divide into smaller arteries as they course
through the lungs to supply the alveoli. The emboli stop in the pulmonary arteries, where they are no
longer physically able to progress, and, in so doing, obstruct the flow of blood distally. It is thought to
take at least several days for venous thrombi to become clinically evident.

Factors influencing thrombosis

Thrombosis is considered to arise from the interplay between the three factors that make up Virchow’s
triad:

• changes in blood flow (stasis or turbulence)

• vessel wall dysfunction

• changes in blood components, leading to hypercoagulability.

The importance of the individual components of Virchow’s triad varies between arterial and venous
thrombosis:

• Turbulence and vessel-wall dysfunction caused by atheromatous plaques are factors in arterial
thrombosis.

• Stasis and hypercoagulability are more relevant in the pathogenesis of venous thrombosis
Risk factors
Transient
• Surgery, especially major, lower limb/pelvis or cancer-related

• Trauma, especially lower limb/pelvis

• Active cancer

• Acute medical admission

• Immobilization (bed rest >3 days)

• Plaster cast

• Pregnancy/puerperium

• Oestrogen administration (combined hormonal contraception, oral hormone therapy)

• Recent long-haul travel (>4 h)

• Central venous catheter

• Heparin-induced thrombocytopenia

• Superficial vein thrombosis

Persistent
• Increasing age

• Body mass index >30 kg/m2

• Ethnicity

• Previous episode of venous thromboembolism

• Inflammatory conditions, e.g. inflammatory bowel disease, systemic lupus

erythematosus, Behçet’s syndrome

• Nephrotic syndrome

• Lower limb paresis, e.g. after stroke

• Heritable thrombophilia (factor V Leiden, prothrombin gene mutation, deficiencies of

antithrombin, protein C or protein S)

• Antiphospholipid syndrome

• Myeloproliferative neoplasms
Deep vein thrombosis – clinical features
• The typical features of DVT include pain and swelling in one leg.

• The leg may be red and warm to the touch.

• There may also be tenderness along the course of the deep veins and
dilation of the superficial

Pulmonary embolism – clinical features

• In about 65% of cases, with pleuritic chest pain and breathlessness, sometimes
accompanied by hemoptysis. Tachypnoea and tachycardia are typically present. Crackles and a
pleural rub over a localized area of pulmonary infarction may be evident on auscultation.

• In another 25%, with isolated breathlessness, sometimes only evident on exertion.

• In the remaining 10%, with more severe features, including syncopal episodes, systolic
hypotension or shock, and myocardial ischemia with associated central chest pain. With this more
severe presentation the patient is tachypnoeic, and has a tachycardia with peripheral shutdown, a
raised jugular venous pulse (JVP) with a prominent α-wave, right ventricular heave, gallop rhythm
and a widely split-second heart sound. Cardiac arrest may occur, typically with pulseless electrical
activity. The severity of presentation depends on both the thrombus burden and the individual’s
cardiopulmonary reserve.

Investigations

ECG

Chest X-ray

Arterial blood gas analysis

Biomarkers of cardiac injury

 ECG / Kumar
• A right ventricular strain pattern may be seen, with T
wave inversion in the inferior (II, III, AVF) and right
precordial (V1–V4) leads.

• The classical ECG is of an ‘S1Q3T3’ pattern, with a

prominent S wave in lead I and a prominent Q wave and
inverted T wave in lead III, but this is present in only a
minority of patients.

• It is more common to see a sinus tachycardia.

Chest X-ray
• This may be normal but more often shows non-specific abnormalities, including

 atelectasis,

 parenchymal abnormalities,

 cardiomegaly,

 elevation of the hemidiaphragm

pleural effusion.

Atelectasis / Clinical case

The patient’s chest radiograph shows small atelectatic changes in
the left lung base (arrow).
Cardiomegaly / Clinical case
Chest x-ray showing moderate cardiomegaly and prominent bibasilar
interstitial markings.

Elevation of hemidiaphragm / Clinical case

Arterial blood gas analysis

• Blood gases typically show hypoxia and hypocapnia, but again these are non-specific findings
and are not always present.

Biomarkers of cardiac injury

• Plasma levels of brain natriuretic peptide (BNP) or its precursor, amino-terminal pro-BNP, may
be elevated because of stretching of the right ventricle, and troponin may be increased because
of right ventricular injury due to strain, but once again these findings are non-specific.
Diagnosis of DVT and PE
Risk scoring

Measurement of D-dimer

Imaging for DVT

Imaging for PE

Diagnosis of DVT and PE

Risk scoring

The diagnostic process starts with assessment of the clinical probability using a clinical
prediction score that takes account of the individual patient’s clinical features, the presence or
absence of risk factors for VTE, and whether an alternative diagnosis is likely to explain the
symptoms and signs. There are a number of clinical prediction scores available, and NICE
recommends the modified two-level Wells score for DVT (Box 29.3) and the two-level Wells
score for PE (Box 29.4); these categorize patients into groups that are likely or unlikely to have
DVT or PE, respectively. Clinical prediction scores standardize clinical assessment and increase
reproducibility among less experienced clinicians. However, in themselves, they do not confirm
or exclude the diagnosis of VTE, and further assessment is necessary.
Measurement of D-dimer

In those considered unlikely to have VTE based on the Wells score, the next step is D-dimer
testing. D-dimer is a fibrin degradation product that can be measured quantitatively in plasma
by highly sensitive laboratory tests, or qualitatively by point-of-care testing of whole blood.
Raised levels indicate activation of the coagulation system but are not specific for VTE, as they
are also seen, for example, with advanced age, infection, inflammation, postoperatively, in
cancer and during pregnancy.

The value of D-dimer in VTE diagnosis is based on its high negative predictive value: that is, VTE
is very unlikely in a patient who has a low pre-test probability of DVT or PE by the Wells score
and in whom D-dimer, measured by a sensitive assay, falls below a predefined cut-off (typically
quoted as ‘normal’). Such patients do not need further diagnostic testing for VTE. With this
approach it must be borne in mind that there is a small failure rate (<2% within 3 months) and
that it does not absolutely exclude VTE.

In contrast, patients whose Wells score indicates that VTE is unlikely but whose D-dimer is raised
(lies above the cut-off value) require formal radiological imaging to confirm or exclude VTE.
Similarly, imaging is also required for all patients whose Wells score indicates that VTE is likely.

Imaging for DVT

The diagnosis of DVT is generally confirmed by ultrasonography of the deep venous system,
which has long replaced the historical gold standard of venography, as it is quicker and non-
invasive.

At a minimum, ultrasonography involves examination of the proximal venous system. Typically,

this includes compression of the popliteal and femoral veins by the ultrasound probe to
 determine whether the vein is compressible or not. This is usually supplemented by direct
thrombus imaging with vein enlargement and assessment of blood flow by Doppler.
Ultrasonography is very sensitive for proximal DVTs (>95%) but less so for distal DVTs (70%).

In general terms, a positive scan will confirm the diagnosis. However, in those with a Wells score
indicating that a DVT is likely, a negative scan, if limited to the proximal venous system, does not
exclude the diagnosis, as it will not identify a proportion of patients who have a distal DVT.
Further assessment of these patients is required (Fig. 29.2)

Ultrasound / Clinical case

• A and B, Ultrasound images of a normal femoral vein
without (A) and with (B) compression. The artery (Art) is
anterior to the vein. After compression, the vein is
completely collapsed, indicating normal compressibility. 

• C and D, Ultrasound images of acute femoral vein thrombus

without (C) and with (D) compression after 1 week of
follow-up.

• The acute DVT (* in C) is heterogeneous. It expands the

vein.

• After compression (D), the vein does not collapse but has an
oval shape indicating an acute DVT based on the
noncompressible but deformable vein.
Imaging for PE
The approach to the diagnosis of PE is similar in principle (Fig. 29.3). When the Wells score indicates that
a PE is unlikely, a negative D-dimer excludes the diagnosis without further investigation.

However, imaging is essential in those who either have a raised D-dimer level or are categorized as likely
to have a PE based on their Wells score.

The most common imaging technique is computed tomographic pulmonary angiography (CTPA)
(Fig.29.5), which is widely available and sensitive and can provide an alternative diagnosis when PE is
excluded. The alternative is ventilation–perfusion (V˙/Q˙) isotope lung scanning, (Fig. 29.6). This test is
performed in two stages:

• a perfusion phase, in which technetium-labelled albumin aggregates are injected intravenously

and blood flow to the lungs is assessed

• a ventilation phase, in which patients inhale radiolabelled xenon or technetium to assess air
delivery to the lungs.

A diagnosis of PE is made if there are mismatched defects in the perfusion scan, indicating impaired
blood flow to the lungs, but normal ventilation because air entry to the lungs is normal. A normal V˙/Q˙
scan excludes the diagnosis of PE. This technique has the advantage of a lower radiation dose and is
preferred in those with renal impairment and allergies to intravenous contrast agents.

Imaging of PE / Kumar
Imaging of PE / Clinical cases

Imaging of PE / Clinical cases

Imaging of PE / Clinical cases

• Proximal acute deep venous thrombosis (DVT)
in a 69-year-old woman.

• Axial CT venogram at the level of the thigh

shows typical findings of DVT in the right
groin.

• An endoluminal filling defect is demonstrated

in the right common femoral vein (arrow),
which is enlarged compared with the left
normal side.
 • Note also extensive peri-focal oedema infiltrating the fat.

• A clot is also demonstrated in the right greater saphenous vein (arrowhead)

Differential diagnosis
Deep vein thrombosis

• Ruptured Baker’s cyst

• Musculo-tendinous – trauma, haematoma, myositis, tendonitis

• Superficial vein thrombosis

• Post-thrombotic syndrome

• Cellulitis

• Osteoarthritis, osteomyelitis, synovitis, fracture, tumour

• Acute arterial occlusion

• Lymphoedema

• Congestive cardiac failure and hypoalbuminaemia – usually cause bilateral leg swelling
Pulmonary embolism

• Chest infection/pneumonia

• Exacerbation of chronic obstructive pulmonary disease

• Asthma

• Pneumothorax

• Congestive cardiac failure

• Acute coronary syndrome

• Costochondritis

• Musculoskeletal pain or rib fracture

• Aortic dissection

• Pericardial tamponade

• Lung cancer

• Primary pulmonary hypertension

• Anxiety/hyperventilation

Timescale of investigation
Diagnostic testing for VTE should be performed urgently and completed within 24 hours of initial
presentation. When imaging is required, a first dose of anticoagulant should be given if it is anticipated
that it will take more than 1 hour to investigate a suspected PE and 4 hours for a suspected DVT.The
approaches described apply only to patients presenting to primary care or emergency departments.
Inpatients and pregnant women should be regarded as high-risk and require appropriate imaging if DVT
or PE is suspected (see p. 1457)
Management

Initial treatment Interventional

of VTE approaches
• Anticoagulant therapy is the standard treatment for VTE. It is traditionally divided into three
phases:

• the acute phase, lasting 5–10 days

• a maintenance phase, lasting a minimum of 3 months

• a long-term phase beyond this.

• The aim of treatment in the initial phase is to prevent thrombus extension and hence reduce
the risk of embolization; the goal thereafter is to prevent thrombus recurrence.
Parenteral anticoagulants

Heparin
Heparin is not a pure substance but a mixture of polysaccharides of different molecular weights of
biological origin. In the UK, all heparins are derived from processed porcine gut mucosa. Heparins are
destroyed in the stomach and must be administered parenterally. Heparin is an indirect anticoagulant
because it does not work directly, but by binding through a specific pentasaccharide sequence to
naturally occurring antithrombin in plasma and inducing a conformational change that increases the
inhibitory activity of antithrombin at least 1000-fold. The result is more rapid inhibition of several of the
activated serine protease coagulation factors, particularly thrombin (factor IIa) and factor Xa. Heparins
are classed as unfractionated heparin (UFH) or as low-molecular-weight heparin (LMWH).
Unfractionated (standard) heparin
• For many years, UFH was the only form of heparin available for the treatment and prevention of
VTE.

• In VTE treatment it is usually administered as an immediate-acting bolus injection, followed by

an initially weight-based intravenous infusion.

• Its use nowadays in the treatment of VTE is largely restricted to particular high-risk settings
where its short half-life, reversibility and lack of renal excretion are advantageous properties.
UFH is rarely used for thromboprophylaxis because its short half-life means that it needs to be
given two or three times daily by subcutaneous injection.

• It is difficult to use in practice because it is necessary to monitor its effect on the APTT regularly
and to adjust the rate of infusion to maintain the APTT ratio (APTT of patient sample compared
to mid-point of the normal range) within a target range: typically, an APTT ratio of 1.5–2.5.

• UFH has a short half-life of 1 hour and, if necessary, can be rapidly reversed with a specific
antidote, protamine sulphate.

• It is not excreted through the kidneys. It carries a small but significant risk of major bleeding,
and of an uncommon but important immunologically mediated, prothrombotic adverse drug
reaction, heparin-induced thrombocytopenia

Low-molecular-weight heparin
LMWHs are the main type of heparin given nowadays because their favourable pharmacokinetic
properties facilitate their use in clinical practice. LMWH is produced by the chemical or enzymatic
degradation of unfractionated heparin, and results in polysaccharide chains of shorter length and
molecular weight than UFH. Since long chains with at least 18 saccharides are required for inhibition of
thrombin by antithrombin, whereas factor Xa is inhibited by shorter chains, the consequence is that,
compared to UFH, the LMWHs inhibit factor Xa to a greater degree than thrombin. LMWH is
administered by subcutaneous injection and peak activity is seen by 4 hours. The half-life of LMWH is
longer than that of UFH at 4 hours. LMWH is excreted through the kidneys and caution is required in
patients with renal impairment. Because of its better bioavailability than UFH, it has the major
advantage of fixed, weight-based dosing, without the need for laboratory monitoring. As a result, the
majority of patients with DVT and many with PE can be treated as outpatients without

hospital admission. Further advantages of LMWH over UFH are that it is at least as safe and effective and
carries a lower risk of HIT. However, LMWH is only partially reversed by protamine sulphate.

In VTE treatment, standard practice for many years has been to give an initial subcutaneous injection of
LMWH while awaiting confirmation of the radiological diagnosis of DVT or PE, and then continuing it
with warfarin until the latter, with its slower onset of action, is providing sufficient anticoagulation for
the LMWH to be stopped, a process that takes at least 5 days. During this time, LMWH is administered,
often by the patients themselves, by subcutaneous injection once or twice daily. In certain groups,
longer-term LMWH is preferred over oral anticoagulants:

• In pregnant women, LMWH is used throughout because it does not cross the placenta.

• In patients with cancer-associated thrombosis, LMWH is more effective than warfarin.

LMWH is also widely used as thromboprophylaxis in patients admitted to hospital or undergoing surgery
and has the advantages over UFH of once-daily administration and lower risk of HIT. LMWH (or an
alternative anticoagulant) also may be used to reduce morbidity and mortality in acute coronary
syndrome, where it is usually given twice daily.

Fondaparinux
Unlike heparins, fondaparinux is a synthetic Penta saccharide. It binds to antithrombin, and because of
its short chain length it inhibits only factor Xa and not thrombin. It is administered by subcutaneous
injection and has a longer half-life than heparin at around 18 hours. It is renally excreted and cannot be
used in those with significant renal impairment. Its effect is not reversed by protamine sulphate.
Oral anticoagulants

Oral anticoagulants

Vitamin K antagonists
These agents are indirect anticoagulants that inhibit the final stage of the synthesis of vitamin K-
dependent proteins in the liver: namely, clotting factors II (prothrombin), VII, IX and X, and the naturally
occurring anticoagulants, protein C and protein S. The main vitamin K antagonist used in the UK is
warfarin. The full anticoagulant effect of warfarin takes at least 5 days because it affects only synthesis
of new proteins; those already circulating or fully formed in hepatocytes are unaffected and decline as a
function of their half-lives, which vary from 6 hours (factor VII) to 60 hours (prothrombin). Therefore, in
the setting of VTE treatment, where an immediate anticoagulant effect is desired, it is necessary
commence with a quick-acting anticoagulant such as heparin, and to continue the latter until warfarin is
providing sufficient anticoagulation on its own.

The anticoagulant effect of vitamin K antagonists is measured using the prothrombin time (PT), which
measures the extrinsic and common pathways of the coagulation system. Because different laboratories
use different reagents with different sensitivities and normal ranges to measure the PT, a system has
been devised to standardize assessment of the degree of anticoagulation by the vitamin K antagonists.
In this system the PT for each patient test (in comparison to the normal PT of the general population not
on anticoagulants) is converted to a standardized ratio, the International Normalized Ratio (INR), and
this enables comparison between results in different laboratories and target ranges defined in clinical
trials to be adopted in routine clinical practice. The higher the INR is, the greater the intensity of
anticoagulation. For most patients on warfarin for VTE treatment, the target INR is 2.0–3.0. A small
proportion of patients – for example, those who have a recurrent VTE episode while the INR is in the
target range – need to be more intensively anticoagulated and the new target range may be set at 3.0–
4.0, reflecting greater prolongation of the PT.

Warfarin is metabolized in the liver and has a half-life of about36 hours. It has a narrow therapeutic
index and a wide range of interactions with dietary factors, alcohol and other drugs. Drug interactions
can be either pharmacokinetic or pharmacodynamic. The former are represented by drugs that either
induce or inhibit the metabolism of warfarin by the cytochrome P450 system, and thereby reduce or
increase warfarin levels and the resulting INR. The latter are exemplified by aspirin and clopidogrel,
which do not affect warfarin levels, but further increase the bleeding risk of warfarin through their
antiplatelet effects. For reasons that are partly genetic, there is considerable variation between
individuals in the dose of warfarin required for the same effect on the INR.

Management of high INRs and bleeding on warfarin

INR >5.0, no bleeding

1. Withhold warfarin

2. Reduce maintenance warfarin dose

3. Investigate cause of elevated INR

INR >8.0, no bleeding or minor bleeding

1. Withhold warfarin

2. If no bleeding, give 1–5mg oral vitamin K

3. If minor bleeding, give 1–3mg intravenous vitamin K

4. Recheck INR within 24 h

Major bleeding

1. Withhold warfarin
 2. Give four-factor prothrombin complex concentrate (PCC) 25–50 u/kg(fresh frozen
plasma 15mL/kg only if PCC not available)

3. Give 5mg i.v. vitamin K

4. Recheck INR following administration of PCCIn the event of bleeding, investigate local
anatomical cause

Oral anticoagulants

Direct oral anticoagulants (DOACs)

DOACs, also called NOACs (non-vitamin K antagonist oral anticoagulants), are a class of anticoagulants
that have been transforming clinical practice since their introduction around 2010. In view of their
increasing use, the clinician should be aware of their pharmacological properties, which are very
different to those of warfarin (Box 29.9).

Four DOACs are currently licensed for treatment of VTE in the UK: three (apixaban, edoxaban and
rivaroxaban) are inhibitors of factor Xa and one (dabigatran) is an inhibitor of factor IIa (thrombin).
Unlike heparin and warfarin, they directly inhibit their target substrates. All are administered orally and
peak levels are seen about 2 hours after ingestion.

• They have a wider therapeutic index than warfarin.

• There is no interaction with dietary factors or alcohol.

• There is limited interaction (compared to warfarin) with other drugs.

• They can be given in a fixed dose with no monitoring – a major clinical advantage.

• They are variably eliminated through the kidneys and have a half-life of around 12
hours.

In the event of major bleeding on DOACs, management should, in general, follow established principles:
 • The DOAC should be stopped.

• Supportive therapy, e.g. intravenous fluids and blood components like red cells, should be
administered as appropriate.

• Consideration should be given to specialty-specific intervention, e.g. endoscopy.

In the event of life-threatening bleeding, specific antidotes are emerging as additional options. In the
case of dabigatran, a monoclonal antibody, idarucizumab, which rapidly binds to and completely
reverses dabigatran, is now widely available. An antidote to the inhibitors of factor Xa, andexanet alfa,
is currently undergoing clinical evaluation.

Management

Initial treatment Interventional

of VTE approaches

Initial treatment/Traditional management

The long-established initial treatment of VTE involves a parenteral anticoagulant, most commonly
subcutaneous low-molecularweight heparin (LMWH); alternatively, intravenous unfractionated heparin
(UFH) or subcutaneous fondaparinux may be used. In addition, an oral vitamin K antagonist, such as
warfarin, is given.

Parenteral anticoagulants are used initially, as they provide almost immediate anticoagulant activity,
whereas warfarin needs at least 5 days to provide therapeutic anticoagulation, as judged by its impact
on the International Normalized Ratio (INR). Heparin or fondaparinux can be stopped and warfarin
continued alone once the INR is 2.0 or more on 2 consecutive days, indicating that the vitamin K
antagonist is now providing sufficient anticoagulation.
Initial treatment of VTE/ DOACs
The introduction of the direct oral anticoagulants (DOACs) into clinical practice around 2010 has had a
major impact on the management of VTE. Four DOACs are currently licensed for VTE treatment: three
direct factor Xa inhibitors (apixaban, edoxaban and rivaroxaban) and one direct thrombin inhibitor
(dabigatran). There are differences between them in the timing of their introduction, based on the large
randomized clinical trials that led to approval for their use.

• Edoxaban and dabigatran are preceded by parenteral anticoagulation (such as LMWH) for 5
days prior to starting the DOAC alone: that is, there is a straight switch from LMWH to edoxaban or
dabigatran on day 6 with no overlap.

• Apixaban and rivaroxaban do not require parenteral anticoagulation and the DOAC is used
alone from the outset, albeit at a higher initial dose, for 7 and 21 days, respectively.The different
treatment models are shown in Fig. 29.7 and the drugs are described further on pages 1014–1016.

Initial treatment of VTE/ Ambulatory care

• Many patients with DVT can be managed on an outpatient basis, admission being reserved for
those with a complex presentation or significant co-morbidities.

• Increasingly, too, low-risk PE can be managed on an outpatient basis or with early discharge
after 24–48 hours.
 • Low-risk patients can be identified using the Pulmonary Embolism Severity Index (PESI) or
simplified PESI (Box 29.5); management as an outpatient or with early discharge might be
considered for this group.

• Higher-risk patients need admission for close observation and administration of high-flow
oxygen.

Original and simplified PESI scores

Original and simplified PESI scores

Role of thrombolysis

Anticoagulants help prevent thrombus extension and recurrence but do not dissolve blood clots, in
contrast to thrombolytic agents. The latter are seldom used in the treatment of VTE because they carry a
higher risk of major bleeding than anticoagulation, including a 2% risk of intracranial haemorrhage.
However, in patients presenting with massive PE characterized by systolic hypotension (blood pressure
≤90mmHg) there is a high risk of early death, and systemic thrombolysis administered intravenously, or
occasionally by catheter infusion directly into the thrombus, may be lifesaving by rapidly restoring
pulmonary perfusion.

The role of thrombolysis in the management of intermediate risk PE – that is, without systolic
hypotension but with evidence of right ventricular dysfunction and raised pro-BNP or troponin levels –
remains controversial. Thrombolysis – either systemic, catheter directed or pharmaco-mechanical – is
occasionally used in the rare setting of management of limb-threatening ilio-femoral vein thrombosis.
Local thrombolysis is also sometimes used in non-limb threatening ilio-femoral vein thrombosis in an
attempt to reduce symptoms and prevent the post-thrombotic syndrome, although there is limited
evidence of long-term benefit.

Management

Initial treatment Interventional

of VTE approaches
Interventional approaches
Surgical embolectomy When patients present with massive PE and thrombolysis is contraindicated,
emergency pulmonary embolectomy can be life-saving. Inferior vena cava filters Occasionally, patients
with newly diagnosed VTE have a contraindication to anticoagulation – for example, active bleeding – or
a major bleeding risk, such as the need for urgent surgery. In such settings an inferior vena cava (IVC)
filter can be inserted by an interventional radiologist to prevent emboli from the deep veins in the leg
reaching the lungs. Contraindications to anticoagulation are usually temporary, and anticoagulant
treatment should be started as soon as it is safe to do so because filters do not entirely prevent
pulmonary emboli and are independently associated with an increased risk of DVT. IVC filters do not
reduce the risk of recurrent PE compared to anticoagulation alone. As IVC filters can give rise to
complications that include migration and embolization, retrievable filters are preferred over permanent
ones and they should be removed as soon as anticoagulation has been safely established.

Complications
Mortality

Associated cancer

Post-thrombotic syndrome

Pulmonary hypertension

Complications / Associated cancer

Cancer-associated thrombosis, the initial description of which is often attributed to Trousseau in the
19th century (Trousseau’s syndrome), is common and 10–20% of all episodes of VTE are diagnosed in
people with cancer. The pathogenesis is multifactorial and includes:

• hypercoagulability resulting directly from the cancer

• the added impact of surgery and/or chemotherapy

• reduced mobility

• use of indwelling central venous catheters that cause local catheter-associated

thrombosis.

The combination of cancer and thrombosis carries a particularly poor prognosis. Up to 5% of patients
who present with a seemingly unprovoked episode of VTE are diagnosed with cancer within 12 months.

Complications / Post-thrombotic syndrome

PTS results from:

• proximal venous occlusion with outflow obstruction

• damage to the venous valves that normally allow blood flow

from superficial to deep and distal to proximal

• development of a collateral circulation

• venous hypertension

• capillary leakage

• localized inflammation.
Complications / Pulmonary hypertension
Following PE, up to 5% of patients remain persistently breathless due to chronic thromboembolic
pulmonary hypertension (CTEPH).

In this condition there is incomplete resolution of pulmonary emboli.

The diagnosis should be suspected in those with persisting symptoms supported by follow-up perfusion
lung scanning, CTPA showing evidence of residual occlusion, and echocardiography suggesting
pulmonary hypertension. Assessment is undertaken by respiratory specialists and a proportion of
patients can be successfully treated surgically with a pulmonary endarterectomy.