Pulmonary Embolism. Pulmonary Embolism. Pulmonary Embolism. PE - Clinical

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1 Pulmonary embolus - a practical approach to investigation and treatment Sam Janes Wellcome Senior Fellow and Respiratory Physician, University College London Background Diagnosis Treatment Common: 50 cases / 200,000 population 50,000 deaths / year in USA Common: 50 cases / 200,000 population 50,000 deaths / year in USA Mortality: without treatment approx. 30% with treatment 2-8% Mortality: without treatment approx. 30% with treatment 2-8% Classification: Acute minor Acute massive Subacute massive Chronic thromboembolic disease Non-thromboembolic Classification: Acute PE Massive Non-massive PE - Clinical Most emboli are multiple & to lower lobes 10% cause infarction Arise from DVT Autopsy studies: PIOPED Trial: 65 90% emboli from legs only 30% had clinical DVT PIOPED symptoms & signs Symptoms: Dyspnoea 73% Pleuritic pain 66% Cough 37% Haemoptysis 13% Signs: Tachypnoea 70% Crackles 51% Tachycardia 30% 4 th H sound 24% Loud P2 23% Syndromes: Pain & haemoptysis 65% Isolated dyspnoea 22% CVS collapse 8%

2 PIOPED symptoms & signs Aetiology But Patients in which PE was excluded had similar symptoms and signs on admission Idiopathic Risk Factors In Care PE / DVT Risk Factors (1) PIOPED Study Immobilisation Surgery within 3/12 Trauma Stroke PH x thromboembolic disease Malignancy PE / DVT Risk Factors (2) Smoking: Age: no evidence that it is related risk rises exponentially Nurses Health Study Obesity Hypertension Travel: all travel > 2-4 h increases risk Idiopathic Thrombophilia Pregnancy Cardiorespiratory disease Occult Ca (pancreas, prostate) OCP (lesser risk) Pregnancy: 1-2 per 7000 (less than thought) usually post-partum PE / DVT Risk Factors (3) Thrombophilia 25-50% of VTE episodes Anti-phospholipid syndrome Factor V Leiden Clotting factor deficiencies Anti-thrombin III Protein C Protein S Usually need to interact with other risk factors eg Factor V Leiden Frequency: 5% general population 20% of VTE Relative Risk: alone x oestrogen therapy x 35 Testing for Thrombophilia? Number to test to prevent an episode very high Factor V Leiden leads to VTE in <1:400 patients Detecting a thrombophilia: does not alter rate of earlier recurrence of VTE May be worthwhile in: Patients under 50 with recurrent idiopathic PEs VTE in family members of more than one generation

3 Cancer Screening in VTE 7-12% of idiopathic VTE present with cancer in next 6-12 mo Should we hunt for it? Most will be picked up by: clinical history & examination CXR routine bloods Further tests are not warranted: 1 year survival of occult cancer is 12% Most have metastases at diagnosis VTE in cancer patients is poor prognostic factor Background Diagnosis Treatment Clinical Examination In itself of limited value to confirm diagnosis BUT clinical probability allows: interpretation of VQ scans combined with D-Dimer reduces need for imaging How to assess probability Previous PE or DVT HR > 100/min Recent surgery or immobilization Clinical signs of DVT + 3 Alternative diagnosis less likely than PE + 3 Haemoptysis + 1 Cancer + 1 Clinical probability: Low 0-1 Intermediate 2-6 High 7 Clinical Probability Breathless and Tachypnoeic (>20) A. No other diagnosis B. A risk factor D-dimers Degradation product of cross-linked fibrin > 500ng/ml in nearly all patients with PE Meta analysis (1337 patients) ve predictive value of D-dimer: 94% A + B = High A or B = Intermediate Neither = Low

4 When not to do D-dimer Pregnancy Cancer Sepsis When non-pe diagnosis is highly likely Anticoagulated Inpatient (eg. Post surgical) Diagnosis: D-Dimers SimpliRED: red cell agglutination Vidas: ELISA MDA: latex The test you use alters the sensitivity & specificity and hence your diagnostic algorithm Use of D-dimer Know which assay your laboratory uses Assay Sensitivity (%) Specificity (%) Rapid ELISA (VIDAS) Immunoturbimetric (MDA) Whole-blood agglutination (simplired) * Using a cut-off of 500μg/l Diagnosis: D-Dimers II Only do D-Dimer after assessing clinical probability Don t bother if high probability A NEGATIVE test excludes PE in: low probability (all three) intermediate probability (Vidas, MDA) Diagnosis : Isotope Lung Scans V/Q Scans can be clear cut Consider if: available on site CXR normal no cardiopulmonary disease Beware: A negative scan excludes PE A minority of high probability scans are false +ve A lot are non-diagnostic!

5 VQ scan - intermediate probability Diagnosis : Leg Ultrasound Patients with PE: 60% have proximal DVT 20% have distal DVT Only 25-50% will be detected by compression US In patients with a clinical DVT a leg US may be the only imaging required A single negative leg US CANNOT be relied upon in suspected PE Diagnosis : Pulmonary Angiography Pulmonary angiogram - normal DSA Gold standard test Mortality <0.5% Morbidity 5% Availability? For subsegmental clot: interobserver disagreement occurs in one third of cases

6 Good Diagnosis : CTPA quantitative (correlates to clinical severity) interobserver agreement! see secondary effects (infarcts/ RV changes) Bad less likely than angiogram to see sub-segmental clot BUT 94% of patients have more proximal clot that is identified Diagnosis : CTPA +V Imaging leg veins Identifies 8-18% DVTs in -ve thoracic scans BUT increased radiation and time < 1% of -ve studies have PEs at 3/12 Donato AA et al Arch Intern Med 163:

7 CTPA vs VQ CTPAs are: quicker rarely followed by other images allow other diagnoses out of hours However. VQs can reduce the No. of CTPAs by ~ 30% (13% require both) Clinical Outcomes in Suspected Acute PE & Negative Helical CT Results in whom Anticoagulation was Withheld Donato AA et al Arch Intern Med 163: retrospective analysis of 433 scans for clinical suspicion of PE excluded 119 (27%) +ve studies & 57 who were anticoagulated follow-up (3/12) was completed 98.4% VTE developed in 4 (1.7%) 33 patients died, 1 of a probable PE (0.4%) Conclusion: CTPA is safe, definitive, minimally invasive test associated with a low 3 month risk of VTE May be comparable to results of ve pulmonary angiography or low-probabililty VQ scan Echocardiography Diagnostic in massive PE Not reliable in sub-massive PE Abnormal in 80% PE Dilated RV & PA regional RV wall abnormalities Intra-cardiac clot Non-invasive guide to filling Exclude differential diagnoses Impact of thrombolysis on RV dysfunction Pre- Post-

8 Diagnosis: Non-massive PE Suspected non-massive pulmonary embolism Lots of tests! What do I ask for? In what order? Suspected non-massive pulmonary embolism Suspected non-massive pulmonary embolism Leg US? Suspected non-massive pulmonary embolism Diagnosis: Massive PE There may be no time for tests! Echo CTPA (if stable) Leg US?

9 Treatment : Thrombolysis Massive PE (circulatory collapse) thrombolysis the earlier the better little evidence single randomised trial: 4 patients thrombolysed lived 4 given heparin died - trial stopped Treatment : Thrombolysis What to give: 50mg bolus Alteplase as MI or Streptokinase over 2 hours Cardiac Arrests 50% of EMD & asystolic arrests in A+E due to PE Very few survive what ever you do In hospital alteplase maybe life-saving (may need to give up to 30 minutes CPR!!) Impact of thrombolysis Impact of thrombolysis Post- Pre- Post- Pre-

10 Thrombolysis Alternatives Doctor, Doctor there s something in my PA. Embolectomy or Right Heart Catheter clot fragmentation can be considered if expertise and facilities are available. Sub-massive PE Treatment : Thrombolysis Sub-Massive PE Evidence suggests patients may have less emergency interventions No difference in mortality Increased Bleeding Current thoughts: Do not to give it Treatment : Anticoagulation LMWH > UFH Likely that half of patients with PE could be managed as outpatients Is a bolus of UFH necessary? - most trials have Are the LMWH equivalent? - probably

11 Treatment : Anticoagulation Give Heparin to those with intermediate / high probability pre-imaging UFH first dose bolus (due to poor cutaneous perfusion) in massive PE rapid reversal may be necessary - warfarin after confirmation Give Warfarin INR Give 4-6 weeks if temporary risk factor Give 3 months for first episode Give at least 6 months for another episode (balance risk of bleeding) Treatment : IVC filters Effective for 12 days No difference in mortality Recurrence may be higher in the filter groups Removable filters???? Pregnancy : Which imaging test should I request? Pregnancy : Treatment LMWH is safe (dose adjustment required) Chest radiography Perfusion only scan V/Q CTPA Pulmonary angiography Background radiation in 9 months Answer: Leg US US Radiologists: UK Radiologists: 0.07 msv 0.8 msv msv msv msv msv 70% recommended V/Q 60% recommended CTPA Warfarin is teratogenic; safe in breast feeding UFH should be given as delivery approaches? Stop 4-6 hours pre-delivery Continue anticoagulation 6 weeks post delivery or 3 months post event You can t diagnose what you don t think of D-dimer tests are not the same Identify the Massive Prevention is better than cure HAPPY CLOTBUSTING!