Epidemiology and diagnostic tests for venous thromboembolism

1
Epidemiology and diagnostic tests for venous
thromboembolism
Edwin JR van Beek, MD PhD FRCR Section of
Academic Radiology University of Sheffield, UK
2
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
3
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

4
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

5
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

6
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 Crohns disease, nephrotic syndrome
• Hyperviscosity (Polycythemia, Waldenstroms
  macroglobulinemia)
• Platelet abnormalities

7
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

8
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?

9
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)

10
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

11
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

12
Points of interest in clinical history

• Onset of symptoms
• Previous VTE
• Family history
• Risk factors (increasing number known!)

13
Chest X-ray findingssuggestive for PE

• Normal
• Peripheral consolidation (Hamptons hump)
• Pleural effusion
• Radiolucency (Westermakr sign)

14
ECG findingssuggestive for PE

• Right bundle branch block
• Right axis shift
• Tachycardia or new onset atrial fibrillation
• S1Q3T3 pattern

15
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

16
Pulmonary angiographySafety

• 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)

17
Lung scintigraphyPIOPED Classification

• Normal (lt1 PE)
• Very low probability (lt10 PE)
• Low probability (lt19 PE)
• Intermediate probability (20-79 PE)
• High probability results (gt80 PE)

18
Lung scintigraphyClassification 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

19
Lung scintigraphyNormal 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 (95CI 0.2-0.4)

20
Lung scintigraphyHigh probability VQ scan

• Obtained in 20-30 of ?PE patients
• 9 studies with 350 patients compared with
  pulmonary angiography
• Pos. Pred.Value 88 (95CI 84-91)

21
Lung scintigraphyNon-diagnostic (V)Q scan

• Obtained in 40-60 of ?PE patients
• 12 studies with 1529 patients compared with
  pulmonary angiography
• PE present 25 (95CI 24-28)

22
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

23
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.

24
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 gt35 of suspected patients
  in AE department.
• Comorbid conditions increase D-dimer levels
  (specificity approximately 50).

25
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

26
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.

27
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)

28
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

29
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!

30
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.

31
Management issues

• Pregnancy
• Children
• Suspected recurrent PE
• Chronic Thromboembolic Pulmonary Hypertension