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Epidemiology and diagnostic tests for venous thromboembolism. Edwin JR van Beek , MD PhD FRCR Section of Academic Radiology University of Sheffield, UK. Personal background. 1980-87 Medical School, Rotterdam, NL 1987 MD Rotterdam, NL 1987-90 Surgical jobs, UK and NL

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epidemiology and diagnostic tests for venous thromboembolism

Epidemiology and diagnostic tests for venous thromboembolism

Edwin JR van Beek, MD PhD FRCR

Section of Academic Radiology

University of Sheffield, UK

personal background
Personal background

1980-87 Medical School, Rotterdam, NL

1987 MD Rotterdam, NL

1987-90 Surgical jobs, UK and NL

1994 PhD Amsterdam, NL (Pulmonary embolism)

1994-99 Radiology training, NL

1999 FRCR, London, UK

venous thromboembolism vte
Venous thromboembolism (VTE)
  • Consists of two clinical pictures:

1. Deep vein thrombosis (DVT)

2. Pulmonary embolism (PE)

  • Intimately related in etiology, treatment and outcome.
  • 50% of proven DVT also have PE
  • 70% of proven PE also have DVT
incidence of venous thromboembolism
Incidence of Venous thromboembolism

*Clinical suspicion PE: 2-3 per 1000/ year

  • Proven PE: 0.5 per 1000/year
  • Clinical suspicion DVT: 2-3 per 1000/year
  • Proven DVT: 1 per 1000/year
  • Japan: 50 to 100-fold less common
risk factors congenital
Risk factors: congenital
  • Deficiencies: antithrombin, protein C, protein S, plasminogen, factor XII
  • Mutations: factor V Leiden (APC-R), prothrombin 20210A
  • Congenital dysfibrinogenemia
  • Hyperhomocysteinemia
  • Thrombomodulin disorders
  • Dysplasminogenemia
  • Anticardiolipin antibodies
  • Excessive plasminogen activator inhibitor
risk factors acquired
Risk factors: acquired
  • Surgery (incl. Orthopaedics, trauma, neurosurgery)
  • Immobilisation: fractures, stroke
  • Malignancy, chemotherapy, central venous catheters
  • Heart failure, chronic venous insufficiency
  • Pregnancy, puerperium, oral contraceptives
  • Albumin loss: Crohn’s disease, nephrotic syndrome
  • Hyperviscosity (Polycythemia, Waldenstrom’s macroglobulinemia)
  • Platelet abnormalities
importance of diagnosis
Importance of Diagnosis

* 70% of patients with clinical suspicion will not have diagnosis confirmed

* Anticoagulants may have serious adverse (haemorrhagic) effects:

- 1 per 100 treatment years: fatal bleeding

- 4%-16% serious hemorrhagic events

risk of missed diagnosis
Risk of Missed Diagnosis

* 30% of patients with untreated PE will suffer fatal second event

* 30% of patients with untreated PE will suffer non-fatal second event:

- pulmonary hypertension risk increase?

- post-thrombotic syndrome risk increase?

role of diagnostic strategy
Role of diagnostic strategy
  • Balance between missed/over-diagnosis
  • Initial risk of recurrent PE: physicians will be likely to treat patients
  • Diagnostic tests are there to:

1. Offer alternative diagnosis

2. Exclude VTE

3. Prove VTE (this affects management least)

main diagnostic aids in suspected pe
Main diagnostic aids in suspected PE
  • Clinical diagnosis (history, examination)
  • ECG, chest X-ray
  • Traditional tests: lung scintigraphy, angiography
  • Newer tests: US, CT, D-dimer, cardiac US, MRA
clinical signs vte
Dyspnea (often sudden onset)

Haemoptysis

Collapse

“Fear of dying”

Redness of leg

Pleural chest pain

Tachycardia

Cyanosis (subclinical)

Coughing

Leg swelling

Tenderness of calf

Clinical signs VTE
points of interest in clinical history
Points of interest in clinical history
  • Onset of symptoms
  • Previous VTE
  • Family history
  • Risk factors (increasing number known!)
chest x ray findings suggestive for pe
Chest X-ray findingssuggestive for PE
  • Normal
  • Peripheral consolidation (“Hampton’s hump”)
  • Pleural effusion
  • Radiolucency (“Westermakr sign”)
ecg findings suggestive for pe
ECG findingssuggestive for PE
  • Right bundle branch block
  • Right axis shift
  • Tachycardia or new onset atrial fibrillation
  • S1Q3T3 pattern
pulmonary angiography
Pulmonary angiography
  • Gold standard
  • Normal angiogram effectively rules out PE
  • Physicians are reluctant to use it:
  • - fear, “invasive”, availability
  • Major changes:
  • contrast agents, catheters, guide wires, DSA
pulmonary angiography safety
Studies before 1990:

2203 patients

5 deaths (0.2%)

42 compl (1.9%)

Studies after 1990

3613 patients

1 death (0.03%)

17 compl (0.47%)

Pulmonary angiography:Safety
lung scintigraphy pioped classification
Lung scintigraphy:PIOPED Classification
  • Normal (<1% PE)
  • Very low probability (<10% PE)
  • Low probability (<19% PE)
  • Intermediate probability (20-79% PE)
  • High probability results (>80% PE)
lung scintigraphy classification discussions
Lung scintigraphy:Classification discussions
  • How low is low probability?
  • PIOPED: very low: 10% PE; low: 16% PE
  • Clinicians do not realize this!!
  • Suggested: normal, high probability and non-diagnostic
lung scintigraphy normal perfusion scan
Lung scintigraphy:Normal perfusion scan
  • Obtained in 20-30% of ?PE patients
  • 3 studies with 693 patients: anticoagulants withheld and follow-up 3-6 months
  • Risk of recurrence: 0.3% (95%CI 0.2-0.4%)
lung scintigraphy high probability vq scan
Lung scintigraphy:High probability VQ scan
  • Obtained in 20-30% of ?PE patients
  • 9 studies with 350 patients compared with pulmonary angiography
  • Pos. Pred.Value: 88% (95%CI 84-91%)
lung scintigraphy non diagnostic v q scan
Lung scintigraphy:Non-diagnostic (V)Q scan
  • Obtained in 40-60% of ?PE patients
  • 12 studies with 1529 patients compared with pulmonary angiography
  • PE present: 25% (95%CI 24-28%)
ultrasonography of the deep venous system
Ultrasonography of the deep venous system
  • Direct visualization of thrombus in PE and DVT
  • Based on 70-90% prevalence of DVT in proven PE.
  • Repeated ultrasonography over 7-10 day period:

- replaces venography in suspected DVT

- may be able to replace angiography in suspected PE

ultrasonography of the deep venous system in suspected pe
Ultrasonography of the deep venous system in suspected PE
  • Single investigation: sens 30%, spec 97%
  • Only to prove PE!
  • Problem: false positive leads to treatment.
  • Cost-effectiveness in doubt.
plasma d dimer
Plasma D-dimer
  • Break-down product of cross-linked fibrin.
  • Only ELISA and recent rapid unitary ELISA reach sensitivity approaching 100%.
  • Able to safely exclude >35% of suspected patients in A&E department.
  • Comorbid conditions increase D-dimer levels (specificity approximately 50%).
helical ct pulmonary angiography studies
Helical CT pulmonary angiography: studies
  • 12 studies CT vs scintigraphy/angiography
  • 1171 patients, prevalence PE 39%
  • Sensitivity 88%, Specificity 92%
  • Problem 1: high prevalence
  • Problem 2: poor results in subsegmental PE
anatomical distribution of pe
Anatomical distribution of PE
  • 3 studies using pulmonary angiography.
  • 1 retrospective and 2 prospective.
  • 15-30% isolated subsegmental PE
  • In all with suspected PE: 5-8% isolated subsegmental PE.
helical ct two management studies
Helical CT: two management studies
  • Study 1: 164 patients: N-D lung scan, normal US.
  • Prevalence PE 24%, follow-up only in 109 patients
  • Recurrent VTE: 6 (5.5%; 95% CI 2-12%)
  • Fatal PE: 1 (1%; 95% CI 0.02% - 4.3%)
  • Study 2: 398 hCT, 285 normal (72%)
  • Follow-up only in 198 (70%)
  • Recurrent PE: 2 (1%; 95% CI 0.12-3.57 %)
  • Fatal PE: 1 (0.5%; 95% CI 0.01-2.75%)
echocardiography for suspected pe
Echocardiography for suspected PE
  • Direct visualization of (central) thrombus
  • Assessment of right ventricular function
  • Measurement of pulmonary arterial pressure
  • Useful in suspected massive PE
  • Potentially useful for therapy monitoring
magnetic resonance angiography
Magnetic Resonance Angiography
  • No ionizing radiation, non-invasive.
  • Promising new technology, fast developments.
  • Pulmonary perfusion studies possible.
  • Early results show similar problems to helical CT: subsegmental PE difficult!
management strategies for suspected pe clinical factors
Management strategies for suspected PE: clinical factors
  • Massive PE: hemodynamic instability.
  • Sub-massive PE: echocardiographic signs of RV dysfunction only.
  • Non-massive PE: no hemodynamic effects detectable.
management issues
Management issues
  • Pregnancy
  • Children
  • Suspected recurrent PE
  • Chronic Thromboembolic Pulmonary Hypertension