venous thromboembolism is an entity comprising deep venous thrombosis and pulmonary embolism, this course enlighten the epidemiology, diagnosis, and treatment of these entities

1. Venous thromboembolism
TSAMO NDOMO Vigny
1st Year resident in Neurology

2. Plan ●Introduction
●Epidemiology
●Risk factors
●Pathophysiology
●Diagnosis
●Paraclinical investigations
●Management
●Differential diagnosis
●Complications
●Conclusion
2

3. Introduction
●Venous thrombosis typically refers to the formation of a platelet and
fibrin clot within the vascular lumen.
●Venous thromboembolism (VTE) includes deep vein thrombosis (DVT)
and pulmonary embolism (PE).
●Pulmonary embolism is regarded as the most common cause of
hospital preventable deaths.
● Clinical symptoms of the thrombus are seen when the clot propagates
enough to have obstruction of vascular flow.
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4. Epidemiology
●About 60% of VTE cases being hospital-acquired, VTE is the leading
preventable cause of death in hospitalized patients.
●The annual incidence of diagnosed venous thromboembolism (VTE) is
1 to 2 events per 1000 of the general population.
●In the United States alone, there are approximately 100000 to 300000
VTE-related deaths reported every year.
●In Europe, this number rises to greater than 500000 deaths annually.
●in Cameroon venous thromboembolism have a prevalence of 4.4 per
1000 admissions and a mortality of 10%.
4

5. Risk Factors
●DVT is considered unprovoked if no clear precipitating risk factor can
be identified.
●Risk factors are either hereditary or more often acquired.
●For provoked DVT, risk factors include
• Cancer,
• Acute medical illness,
• Surgery,
• Trauma,
• Immobility (often in hospital and
lasting at least three days),
• Obesity,
• Inflammatory diseases/infection,
• Hormone therapy (oestrogen
containing),
• Pregnancy (particularly the postpartum
period),
• Long distance travel,
• Recent hospitalisation,
• Antiphospholipid syndrome (APS).
5

6. Risk Factors
●Primary varicose veins constitute a minor risk factor only.
●More recently, prolonged computer related “seated immobility
syndrome” has also been recognised as a potential risk factor.
●The most common inherited risk factor is a non-O blood type, which is
associated with double the risk of VTE.
●Another common thrombophilia is heterozygous factor V Leiden gene
polymorphism, which may increase the risk of VTE by a factor of 3 to 8
in selected populations.
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7. Risk Factors
●Severe thrombophilia comprising homozygous factor V Leiden,
deficiency of antithrombin, protein C or protein S, and APS increases
the risk of DVT by a factor of 20 to 80.
●Important risk factors for arterial thromboembolism such as
hypertension and diabetes are also risk factors for VTE, but their
significance is far less prominent.
●For patients with cancer, an externally validated clinical prediction
model incorporating D dimer and only one clinical factor (tumour site
category) has been shown to predict the risk of VTE.
7

8. Pathophysiology
●the main pathophysiological factors implicated in thrombosis are
considered to be increased procoagulant in the blood, vein wall
damage, and impaired venous flow (Virchow’s triad).
●Impaired flow, known also as venous stasis, may result from external
compression by aneurysms, tumours, or the right common ilac artery.
●which compresses and causes fibrosis of the underlying left common
iliac vein in MayeThurner syndrome (iliac vein compression syndrome).
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9. Pathophysiology
●The thrombotic process leads to increased outflow resistance and
decreased outflow volume with increased venous pressure, which,
together with perivascular inflammation, is responsible for the
characteristic symptoms and signs of DVT.
●The most extreme clinical presentation of DVT may occur when there
is occlusion of the common femoral and external iliac veins.
●Complete obstruction of the outflow of all deep and superficial veins of
the limb, as well as collaterals, may occur and is termed phlegmasia
cerulea dolens
9

10. Pathophysiology
●Clinical symptoms of the thrombus are seen when the clot propagates
enough to have obstruction of vascular flow.
●If the clot dislodges, it can then embolize to a distant site.
●The most common site of embolization for these clots is in the
pulmonary vasculature.
●Obstruction to pulmonary vascular flow can cause impaired gas-
exchange, alveolar edema, or even pulmonary alveolar necrosis.
10

11. Pathophysiology
●Chronic repetitive pulmonary embolization can lead to increased
pulmonary vascular resistance and, eventually, pulmonary
hypertension.
●In the presence of cardiac abnormalities such as a patent foramen
ovale or an atrial septal defect.
●paradoxical embolism of the clot into the systemic arterial vascular can
occur.
11

12. Pathophysiology
●Progressive right heart failure is the
usual cause of death from PE.
● As pulmonary vascular resistance
increases, RV wall tension rises and
causes further RV dilatation and
dysfunction.
●Underfilling of the LV may lead to a fall in
left ventricular cardiac output and
systemic arterial pressure, thereby
provoking myocardial ischemia due to
compromised coronary artery perfusion.
12

13. Diagnosis
●History taking
○It should be based on the identification of earlier mentioned
risks factors.
○in 40% of patients with PE, no predisposing factors are found.
●Signs and symptoms
○The diagnosis is challenging because symptoms and signs are
nonspecific.
○In most cases, PE is suspected in a patient with:
■ Dyspnoea,
■ Chest pain,
■ Presyncope or syncope
■ Haemoptysis.
■ Tachypnea
13

14. Diagnosis: signs and symptoms (Cont…)
●Dyspnoea may be acute and severe in central PE; in small peripheral
PE, it is often mild and may be transient.
●In patients with preexisting heart failure or pulmonary disease,
worsening dyspnoea may be the only symptom indicative of PE.
●Chest pain is a frequent symptom of PE and is usually caused by
pleural irritation due to distal emboli causing pulmonary infarction.
●In central PE, chest pain may have a typical angina character, possibly
reflecting RV ischaemia, and requiring differential diagnosis from an
acute coronary syndrome or aortic dissection.
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15. Diagnosis: signs and symptoms (Cont…)
●Symptoms from calf DVT may vary, and even be asymptomatic,
depending on the collateral drainage.
●It should be noted that up to 80% of DVT cases may not be clinically
apparent, with pain being the only feature.
●In DVT cases located at iliofemoral level the leg is usually considerably
swollen and painful, with decreased mobility and oedema from the
groin and distally due to limited venous collateral drainage in the
pelvic region.
●Prominent superficial veins may be seen.
●For DVT originating in the iliac veins, back pain may be an early
feature.
15

16. Diagnosis: Physical exam (Cont…)
●Physical findings, if present at all, may simply consist of mild palpation
discomfort in the lower calf.
●Massive DVT is much easier to recognize.
●The patient presents with severe thigh swelling and marked
tenderness when palpating the inguinal area and common femoral
vein.
●In extreme cases, patients will be unable to walk or may require a
cane, crutches, or walker.
●Patients with massive PE present with systemic arterial hypotension
and usually have anatomically widespread thromboembolism.
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17. Diagnosis: Physical exam (Cont…)
●Patients with mild to moderate PE, have both normal right heart
function and normal systemic arterial pressure.
●They have an excellent prognosis with adequate anticoagulation.
●The presence of pulmonary infarction usually indicates a small PE, but
one that is exquisitely painful, because it lodges peripherally, near the
innervation of pleural nerves.
●Pleuritic chest pain is more common with small, peripheral emboli.
●Larger, more central PEs can occur concomitantly with peripheral
pulmonary infarction.
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18. Diagnosis: Physical exam (Cont…)
●Nonthrombotic PE
●Possible etiologies include
○Fat embolism after blunt trauma and long bone fractures,tumor embolism, bone
marrow.
○Air embolism.
○Cement embolism and bony fragment embolism can occur after total hip or knee
replacement.
○Foreign bodies as Intravenous drug users may inject themselves with a wide array of
substances, such as hair, talc, or cotton.
○Amniotic fluid embolism occurs when fetal membranes leak or tear at the placental
margin.
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19. Diagnosis: Physical exam (Cont…)
●Clinical syndromes
●Dyspnea, syncope, hypotension, or cyanosis indicates a massive PE.
●Pleuritic pain, cough, or hemoptysis often suggests a small embolism
located distally near the pleura.
●Some patients have occult PE and an overt coexisting illness such as
pneumonia or heart failure.
●In such circumstances, clinical improvement often fails to occur despite
standard medical treatment of the concomitant illness.
●This situation can serve as a clinical clue to the possible coexistence of
PE.
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20. Diagnosis
●Pre-test probability of DVT can be
assigned to patients, aiding decision
making strategies.
●The most thoroughly studied and
validated clinical decision score is the
Wells DVT score , which categorizes
the pre-test probability scores of
DVT(see next slide)
○ Into two
■ DVT likely if score ≥ 2
■ Unlikely if score < 2 or
○ Three groups
■ High likelihood of DVT if ≥ 3;
■ Moderate likelihood if 1 - 2;
■ Low likelihood if ≤ 0
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21. Well score for prediction of DVT
21

22. ●Revised Geneva criteria
●It’s a decision tool that helps determine
probability of pulmonary embolism.
●It can be used as an alternative to the
Wells’ pulmonary embolism score.
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23. Paraclinical investigations
●D dimer measurement
●D-dimer levels are elevated in plasma in the presence of acute
thrombosis because of simultaneous activation of coagulation and
fibrinolysis.
●The negative predictive value of D-dimer testing is high, and a normal
D-dimer level renders acute PE or DVT unlikely, as it’s normal (<500
ng/mL and age×10 µg/L for patients above 50 years) in more than 95%
of patients without PE.
●D-dimer is also more frequently elevated in patients with cancer, in
hospitalized patients, in severe infection or inflammatory disease, and
during pregnancy.
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24. Paraclinical investigations
●Other biological tests
●Serum troponin levels increase in RV microinfarction.
●Myocardial stretch often results in elevation of brain natriuretic
peptide or NT-pro-brain natriuretic peptide.
●Elevated cardiac biomarkers predict an increase in major
complications and mortality from PE.
●Contrary to classic teaching, arterial blood gases lack diagnostic utility
for PE, even though both the PO2 and PCO2 often decrease.
●Among patients suspected of PE, neither the room air arterial PO2 nor
calculation of the alveolar-arterial O2 gradient can reliably differentiate
or triage patients who actually have PE at angiography.
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25. Paraclinical investigations
●Computed tomographic pulmonary angiography
●It’s the principal imaging test for the diagnosis of PE
●Multidetector CTPA is the method of choice for imaging the pulmonary
vasculature in patients with suspected PE.
●It allows adequate visualization of the pulmonary arteries down to the
subsegmental level.
●It has a sensitivity of 83% and a specificity of 96%.
●Multidetector-row spiral CT can image small peripheral emboli up to
the 6th order branches.
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26. Paraclinical investigations
●The CT scan also obtains excellent images of the RV and as In patients
with PE, RV enlargement on chest CT indicates a fivefold increased
likelihood of death within the next 30 days compared with PE patients
with normal RV size on chest CT.
●In patients without PE, the lung parenchymal images may establish
alternative diagnoses not apparent on chest x-ray that explain the
presenting symptoms.
●Remain an invasive test.
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27. Paraclinical investigations
●Lung scintigraphy
●The planar ventilation/perfusion [V/Q (lung scintigraphy)] scan is an
established diagnostic test for suspected PE.
●Perfusion scans are combined with ventilation studies, using tracers such as
xenon-133 gas, krypton-81 gas, technetium-99m-labelled aerosols, or
technetium-99m-labelled carbon microparticles.
●The purpose of the ventilation scan is to increase specificity as in acute PE,
ventilation is expected to be normal in hypoperfused segments
(mismatched).
●Can be used in outpatients with a low clinical probability and a normal chest
X-ray, in young (particularly female) patients, in pregnant women, in patients
with history of contrast medium-induced anaphylaxis, and patients with
severe renal failure.
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28. Paraclinical investigations
●Results are frequently classified according to the criteria established in
the PIOPED study.
○Normal scan (excluding PE),
○High-probability scan (considered diagnostic of PE in most patients)
○Non-diagnostic scan.
●Prospective clinical outcome studies suggested that it is safe to
withhold anticoagulant therapy in patients with a normal perfusion
scan.
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29. Paraclinical investigations
●Magnetic resonance angiography
○Used when ultrasound is equivocal.
○It’s an excellent imaging modality to diagnose DVT, However it has a low sensitivity,
isn’t always available in emergencies settings and presents a high proportion of
inconclusive results.
○Detects large proximal PE but is not reliable for smaller segmental and subsegmental
PE.
●ELECTROCARDIOGRAM
○The most cited abnormality, in addition to sinus tachycardia, is the S1Q3T3 sign: an S
wave in lead I, Q wave in lead III, and inverted T wave in lead III.
○This finding is relatively specific but insensitive.
○Perhaps the most frequent abnormality is T-wave inversion in leads V1 to V4.
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30. Paraclinical investigations
●Echocardiography
●Acute PE may lead to RV pressure overload and dysfunction, which can be
detected by echocardiography.
●suggested by the combination of:
○ Pulmonary ejection acceleration time (measured in the RV outflow tract) <60ms
○ Peak systolic tricuspid valve gradient <60 mmHg (‘60/60’ sign),
○ Depressed contractility of the RV free wall compared to the ‘echocardiographic’ RV apex
(McConnell sign),
●Good to note that a negative result cannot exclude PE.
●In case of acute PE, it May detect increased RV wall thickness or tricuspid
insufficiency jet velocity beyond values compatible with acute RV pressure
overload (>3.8 m/s or a tricuspid valve peak systolic gradient >60 mmHg).
●Important to rule out differential diagnosis.
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31. Diagnostic algorithm for
Pulmonary Embolism
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32. Management
●Aims:
○Stabilize the patient.
○Prevent propagation of DVT and PE.
○Assure a good lung perfusion.
○Prevent propagation of DVT and PE, and reduce the risk of
early and long term recurrent VTE.
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33. Pulmonary embolism severity index score (PESI
score)
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34. Management
●Anticoagulation
●Anticoagulation treatment for DVT may be divided into three distinct
phases:
○Initial treatment phase (up to 10 days) with the aim of rapidly instigating
anticoagulation therapy to prevent propagation of DVT and PE;
○Principal treatment phase (first three months) to maintain therapeutic levels of
anticoagulation to prevent propagation of DVT and PE, and reduce the risk of early
recurrent VTE;
○Extended treatment phase (beyond three months, with no scheduled stop date) with
the specific aim of reducing the long term risk of recurrent VTE.
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35. Management
●Indirect anticoagulants, including the heparins, fondaparinux, or
danaparoid, require the presence of antithrombin for inhibiting factor
IIa (thrombin) and factor Xa, while direct anticoagulants act without the
requirement of any co-factor.
●Unfractionated heparin (UFH) inhibits both factor IIa and factor Xa with
a Xa/IIa inhibition ratio of 1:1, while in low molecular weight heparins
(LMWH) the Xa/IIa inhibition ratio varies between 2:1 and 4:1 and
depends on the molecular weight of the LMWH.
●LMWHs with a smaller mean molecular weight are excreted
predominantly via the kidney and may therefore accumulate in
patients with renal insufficiency.
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36. Management
●VKAs, such as warfarin, acenocoumarol, and phenprocoumon, are
administered orally and inhibit the gamma carboxylation of
coagulation factors II, VII, IX, and X, a modification that is necessary for
their functional activity.
●There is a transient hypercoagulable shift during the initiation of VKA,
Consequently, it is essential that effective overlapping anticoagulation
is ensured with heparins or fondaparinux during the initiation of VKA
therapy.
●Parenteral anticoagulation should only be discontinued when it has
been given for a minimum of five days and a therapeutic international
normalised ratio (INR)> 2.0 is achieved with VKA and maintained over
two consecutive days.
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37. Management
●Direct anticoagulants do not require the presence of antithrombin and
include:
●Thrombin (IIa) inhibitors hirudin and argatroban.
●DOAC dabigatran, which inhibits factor IIa.
●DOACs that inhibit factor Xa, they are also called oral factor Xa
inhibitors, and include apixaban, edoxaban, and rivaroxaban.
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38. Management
●Unfractionated heparin
○Unfractionated heparin is currently only used in special clinical situations, such as
severe renal insufficiency, haemodialysis, pending interventions, or for critically ill
patients.
○Body weight should be assessed and activated partial thromboplastin time (APTT)
evaluation is necessary for accurate and safe administration.
○An APTT ratio of 1.5 to 2.5 should be reached within 24 hours of starting treatment.
○Monitoring of antifactor Xa activity (target 0.3 to 0.7 IU/mL) can produce more reliable
results than APTT monitoring.
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39. Management
●Low molecular weight heparins
●LMWHs are given subcutaneously, with the dose adjusted for patient
body weight.
●LMWHs may be administered once or twice daily according to renal
function.
●Monitoring is only recommended in special situations;
●target peak values of antifactor Xa activity four hours after the last
injection of 0.6 to 1.0 international units (IU)/mL for twice daily
administration (b.d.), and 1.0 to 2.0 IU/mL for once daily (o.d.)
39

40. Management: Initial anticoagulation
●Parenteral anticoagulation
●In patients with high or intermediate clinical probability of PE
anticoagulation should be initiated while awaiting the results of
diagnostic tests.
●This is usually done with subcutaneous, weight adjusted low-molecular
weight heparin (LMWH) or fondaparinux, or i.v. unfractionated heparin
(UFH).
●Equally rapid anticoagulant effect can also be achieved with a
nonvitamin K antagonist oral anticoagulant (NOAC).
40

41. Management
●LMWH and fondaparinux are preferred over UFH for initial
anticoagulation in PE, as they carry a lower risk of inducing major
bleeding and heparin-induced thrombocytopenia.
●Neither LMWH nor fondaparinux need routine monitoring of anti-Xa
levels.
●Use of UFH is nowadays largely restricted to patients with overt
haemodynamic instability or imminent haemodynamic
decompensation in whom primary reperfusion treatment will be
necessary.
●UFH is also recommended for patients with serious renal impairment
[creatinine clearance (CrCl) <_30 mL/min] or severe obesity.
●If LMWH is prescribed in patients with CrCl 15 - 30 mL/min, an adapted
dosing scheme should be used.
41

42. Management
●Non-vitamin K antagonist oral anticoagulants
●NOACs are small molecules that directly inhibit one activated
coagulation factor, which is thrombin for dabigatran and factor Xa for
apixaban, edoxaban, and rivaroxaban.
●NOACs can be given at fixed doses without routine laboratory
monitoring.
●There are fewer interactions when NOACs are given concomitantly
with other drugs.
●Can be safely used in patients with a CrCl > 30mL/min.
42

43. Management
●Rivaroxaban
●Rivaroxaban is started without initial parenteral therapy but requires a
higher dose (15 mg b.d.) for three weeks, followed by the standard
treatment dose of 20 mg o.d.
●A rivaroxaban dose of 20 or 15 mg should be taken with food, which
improves its bioavailability.
●A lower dose of 10 mg o.d. is used for extended therapy.
●Contraindicated in gastrointestinal cancers and pregnancy.
43

44. Management
●Vitamin K antagonists
●VKAs have been the gold standard in oral anticoagulation for more
than 50 years.
●When VKAs are used, anticoagulation with UFH, LMWH, or
fondaparinux should be continued in parallel with the oral
anticoagulant for >_5 days and until the international normalized.
●Warfarin may be started at a dose of 10 mg in younger (e.g. aged <60
years), otherwise healthy patients and at a dose <_5 mg in older
patients.
●The daily dose is adjusted according to the INR over the next days,
aiming for an INR level of 2.0 to 3.0.
●Anticoagulation control and may be associated with a reduced risk of
bleeding, but does not reduce the risk of thromboembolic events or
mortality.
44

45. Management: Reperfusion treatment
●Systemic thrombolysis
●Thrombolytic therapy leads to faster improvements in pulmonary
obstruction, PAP, and PVR in patients with PE, compared with UFH
alone;
●The greatest benefit is observed when treatment is initiated within 48h
of symptom onset, but thrombolysis can still be useful in patients who
have had symptoms for 6 to14 days.
●Thrombolytic therapy is associated with a significant reduction in the
risk of haemodynamic decompensation or collapse, but is associated
to an increased risk of severe extracranial and intracranial bleeding.
45

46. Thrombolytic regimens, doses, and contraindications
46

47. Management: Reperfusion treatment
●Percutaneous catheter-directed treatment
○ Mechanical reperfusion is based on the insertion of a catheter into the pulmonary
arteries via the femoral route.
○ Different types of catheters are used for mechanical fragmentation, thrombus
aspiration, or more commonly a pharmacomechanical approach combining
mechanical or ultrasound fragmentation of the thrombus with in situ reduced-dose
thrombolysis.
●Surgical embolectomy
○ Surgical embolectomy in acute PE is usually carried out with cardiopulmonary bypass,
without aortic cross-clamping and cardioplegic cardiac arrest, followed by incision of
the two main pulmonary arteries with the removal or suction of fresh clots.
○ Indicated in patients with high risk of PE
47

48. Management: Reperfusion treatment
●Vena cava filters
●The aim of vena cava interruption is to mechanically prevent venous
clots from reaching the pulmonary circulation.
●Most devices in current use are inserted percutaneously and can be
retrieved after several weeks or months, or left in place over the long-
term, if needed.
●Potential indications include
○VTE and absolute contraindication to anticoagulant treatment,
○recurrent PE despite adequate anticoagulation,
○primary prophylaxis in patients with a high risk of VTE.
48

49. Summary of the management of acute pulmonary embolism
49

50. Differential diagnosis
●Since pulmonary embolism has a very
heterogeneous clinical presentation ranging from
dyspnea to sudden cardiac arrest.
●The differential diagnosis of PE is extensive and
includes:
○Acute coronary syndrome
○Stable angina
○Acute pericarditis
○Congestive heart failure
○Malignancy
• Cardiac arrhythmias
• Pneumonia
• Pneumonitis
• Pneumothorax
• Vasovagal syncope
50

51. Complications
●The major complications associated with pulmonary
embolism (PE) include the following.
○Recurrent thromboembolism
○Chronic thromboembolic pulmonary hypertension:
○Right heart failure
○Cardiogenic shock
51

52. Conclusion
●Pulmonary embolism (PE) occurs when there is a disruption to the flow
of blood in the pulmonary artery or its branches by a thrombus that
originated somewhere else.
●In deep vein thrombosis (DVT), a thrombus develops within the deep
veins, most commonly in the lower extremities.
●It present a high frequency in hospitalized patients.
●Clinicians should keep a high suspicious index for pulmonary
embolism.
●Pulmonary angiogram remains the gold standard of diagnosis
●Treatment rely on non vitamin K oral anticoagulants.
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53. Bibliography
●Harrison's Principles of Internal Medicine, 21st Edition.
●2019 ESC Guidelines for the diagnosis and management of acute
pulmonary embolism developed in collaboration with the European
Respiratory Society (ERS).
●European Society for Vascular Surgery (ESVS) 2021 Clinical Practice
Guidelines on the Management of Venous Thrombosis.
●Management of PE, American college of cardiology, 2020.
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