Acute Pulmonary Embolism

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Acute Pulmonary Embolism

• Peter DeLong MD
• Pulmonary and Critical Care Medicine
• DHMC
• December 15, 2008

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What we will cover

• Definition
• Epidemiology
• Risk factors
• Diagnosis
• Presentation
• tests
• algorithm
• Treatment
• Risk stratification
• Duration of therapy

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Monday mornings can be hardfor everyone.
This will be fast I will try to keep you awake
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Definition

• Blood clot, usually from the deep veins of the
  leg, also air, fat, tumor, that occludes
  pulmonary vasculature

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Epidemiology

• PE is a major cause of death in the United
  States, with as many as 650,000 cases/yr
  
• 50,000 to 200,000 fatalities annually.
• 400,000 diagnoses of PE are missed in the
  United States annually.
  
• Most deaths from PE are due to failure to
  diagnose rather than failure to treat
  adequately.
  
• Two thirds of patients die within 1 hour of
  symptom onset this is the golden hour.

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Epidemiology

• Mortality is 15 within 3 months after
  occurrence
  
• In 25 of PE, the initial manifestation is death

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Risk Factors

• Virchows triad
• Stasis
• Venous injury/endothelial damage
• Hypercoagulability
• Most patients have several of these

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Risk Factors

• Inherited
• Factor V leiden
• Prothrombin gene mutation
• Low protein C, protein S, antithrombin III
• Family history of VTE
• Acquired
• Age
• Smoking
• Obesity
• immobility
• Malignancy
• APL Ab syndrome venous and arterial
• Hyperhomocysteinemia (can be acquired) venous
  and arterial
  
• OCPs or hormone replacement
• Atherosclerosis
• Trauma, surgery, hospitalization
• Infection
• Long haul air travel

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Who gets Evaluated For Thrombophilia?

• Patients in whom there is a high clinical
  suspicion for underlying disorder
  
• PE not associated with acquired risk factor
• Can be after first event!
• Family history
• Initial evaluation directed towards most common
• Most common
• Factor V Leiden
• Prothrombin gene mutation
• APL Ab syndrome
• Hyperhomocysteinemia
• Less common
• Protein CS deficiency, ATIII deficiency

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Diagnosis

• pathophysiology is complex and results in
  variable clinical presentation
  

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Acute PE Pathophysiology

• Gas exchange abnormalities
• Right to left shunt
• Leads to
• Hypoxemia
• Increased a-A gradient
• V/Q MM
• Increased dead space
• Respiratory alkalosis from hyperventilation
• Often a sign of increased dead space and impaired
  minute ventilation
  
• may suggest massive PE

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Acute PE Pathophysiology

• Hemodynamic abnormalities
• Depends on size of embolus
• Increased vascular resistance/RV afterload
• May cause RV dilation, hypokinesis, tricuspid
  regurgitation, FAILURE
  
• Interventricular flattening, impaired LV filling
• Increased wall stress and ischemia

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DiagnosisSymptoms and Signs

• Symptoms
• Dyspnea
• Chest pain (pleuritic)
• Apprehension
• Cough
• Hemoptysis
• Syncope
• Palpitations
• Wheezing
• Leg pain
• Leg swelling

• Signs
• Tachycardia
• Tachypnea
• hypoxemia
• Accentuated S2
• Fever
• Diaphoresis
• Signs of DVT
• Cardiac murmur
• Jugular venous distention
• Cyanosis
• Hypotension

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DiagnosisLaboratory Evaluation

• D-dimer
• Non specific measure of fibrinolysis
• Measured by ELISA
• High sensitivity (positive in presence of dz)
• High negative predictive value (dz is absent when
  test is negative) in the outpatient setting
  
• Useful in outpatient setting/emergency room, not
  an inpatient test for ruling out PE

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DiagnosisChest XR

• CXR
• Most often normal
• May show collapse, consolidation, small pleural
  effusion, elevated diaphragm.
  
• Uncommon findings include
• Westermarks sign
• Dilation of vessels proximal to embolism
• Hamptons hump
• Pleural based opacities with convex medial
  margins
  

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DiagnosisECG

• ECG may show
• Complete or incomplete RBB
• T wave inversions anteriorly, S1Q3T3
• The latter is very overrated..

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DiagnosisVQ Scan
Ventilation
Perfusion
Mismatch
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DiagnosisV/Q scans

• Old standard
• Currently reserved for
• Renal impairment
• IV contrast allergies
• Pregnancy
• Chronic PE (controversial)

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DiagnosisCT scan New Standard

• Data suggests CT is as accurate as invasive
  angiography (gold standard)
  
• Negative predictive value of 99
• Quiroz et al, JAMA 2005

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DiagnosisSpiral CT/ Multislice
Main Pulmonary Artery
Ascending Aorta
Descending Aorta
Rt Pulmonary Artery
Lt Pulmonary Artery
Thrombus
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Pulmonary Angiogram
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DiagnosisMRI MR Angiogram

• Very good to visualize the blood flow.
• Almost similar to invasive angiogram

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A word about test Interpretation

• Bayes theorem
• Interpretation is based on an assessment of the
  likelihood of a given outcome
  
• Therefore pretest probability impacts
  interpretation of test results
  
• The level of clinical suspicion is primary in
  diagnosis of PE!!
  
• Even in the age of CT scans..

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Another word about test Interpretation

• As with the discrepancy between NYHA class and
  EF
  
• there is poor correlation between radiographic
  clot burden and symptoms in PE
  
• So you must evaluate and manage the patient
  clinically

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Diagnostic algorithm
Outpatient/ED
Inpatient
D-dimer
normal
Elevated
No PE
Chest CT
3rd gen scanner
Ist gen scanner
No PE PE
No PE PE
Ultrasound of leg veins
DVT No DVT
PAgram if continued clinical suspicion
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You have diagnosed a PEWhat now?

• (heparin, then.)
• Risk stratification
• Essentially based on hemodynamic stability
• Elevated biomarkers troponins, BNP should prompt
  ECHO
  
• Some argue for routine ECHO

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ECHO for Risk Stratification

• Insensitive for diagnosis but can risk stratify
  in patients with known PE
  
• In normotensive patients RV dysfunction is an
  independent risk factor for early death
  
• Regional RV dysfunction with free wall apical
  sparing is thought to be specific for PE
  (McConnells sign)

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Risk stratification algorithm
Unstable/shock
Hemodynamically stable/no shock
BNP BNP (RV on CT) Troponin troponin (RV on CT
)
ECHO
No RV dysfunction RV dysfunction
Fibrinolysis, embolectomy
anticoagulation
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TreatmentAnticoagulation

• Mainstay of therapy
• Unfractionated heparin for PTT 60-80 secs
• Preferred in pts undergoing further therapy as it
  can be reversed
  
• Weight based nomograms are effective for
  initiating therapy
  
• LMWH
• More predictable response
• No dose adjustments
• Renally cleared. Some some pts need adjustments
• Kidney dz, pregnancy, massive obesity may need
  anti factor Xa monitoring
  
• Usefulness questioned as correlation with
  antithrombotic effect not clear

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Treatment

• Warfarin
• Vitamin K antagonist
• Dose response variation may be in part
  attributable to the vitamin K epoxide reductase
  complex 1 (VKORC1)
  
• Testing not usually performed

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TreatmentNewer agents

• Fondaparinux
• Synthetic pentasaccharide with anti- Xa activity
• Once daily
• No adjustments
• No risk of HIT

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Treatment ComplicationsHIT

• Both UFH and LMWH can cause HIT
• LMWH much less so
• HIT from IgG against heparin platelet factor IV
  complex
  
• Screen when platelets drop by 50
• if suspected, stop all heparin
• Start direct thrombin inhibitor like lepirudin or
  argatroban

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TreatmentThrombolytics

• T-PA (alteplase) FDA approved for PE
• 100 mg infused over 2 hrs
• no difference in mortality or recurrent PE at 90
  days compared to UFH

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Treatment

• Surgical embolectomy requires a specialized
  center
  
• Can be safe
• Can be effective
• Small published numbers
• Catheter directed embolectomy
• Emerging as effective therapy when fibrinolysis
  cannot be used
  
• Can be performed up to 5 days after event

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TreatmentDuration algorithm
PE
Risk stratify
Not high risk High risk
Anticoagulation fibronlysis/embolectomy
Heparin or heparin LMWH fondaparinux
Warfarin, 6 mos
Stop if due to trauma/surgery No signs of DVT
If idiopathic, continue lifetime
If thrombophilic, continue lifetime
If sxs DVT, doppler until clot resolved
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Recommendations

• From the evidence-based recommendations of the
  Seventh American College of Chest Physicians
  (ACCP) Consensus Conference on Antithrombotic
  Therapy

Buller, HR, Agnelli, G, Hull, RD, et al.
Antithrombotic therapy for venous thromboembolic
disease the Seventh ACCP Conference on
Antithrombotic and Thrombolytic Therapy. Chest
2004 126401s
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Recommendations

• Therapy of acute deep vein thrombosis or
  pulmonary embolism should be initiated with IV
  heparin

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Recommendations

• Heparin therapy should be continued for at least
  five days.
  
• Oral anticoagulation should be overlapped with
  heparin therapy for four to five days.
  
• Heparin and warfarin therapy can be initiated
  simultaneously, with heparin therapy discontinued
  on day five or six if the INR has been
  therapeutic for two consecutive days.
• Longer periods of initial heparin therapy may be
  considered in the case of massive pulmonary
  embolism or iliofemoral thrombosis.

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Recommendations

• LMW heparin may be used in place of
  unfractionated heparin.
  
• Dosing requirements are individualized for each
  product.

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Recommendations Duration of therapy

• First thromboembolic event in the context of a
  reversible risk factor
  
• -- treated for three to six months
• Idiopathic first thromboembolic event
• -- AT LEAST full six months of treatment
• -- further therapy at discretion of clinician
  
  
• Recurrent venous thrombosis or a continuing risk
  factor -- treated indefinitely.
  

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Recommendations

• IVC filter placement is recommended when
• -- anticoagulation is contraindicated
• -- recurrent thromboembolism despite adequate
  anticoagulation
  
• -- chronic recurrent embolism with pulmonary
  hypertension
  
• -- high-risk of recurrent embolization
• -- conjunction with the performance of
  pulmonary embolectomy or endarterectomy

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TreatmentIVC filter

• With filter 5 risk of recurrent pulmonary
  embolus, especially after 6 mos.
  
• complication of leg swelling can occur.
• anticoagulation is continued if possible.

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Summary

• Heparanize (or anticoagulate somehow)
• Think about pre-test probability
• Think about risk stratification beyond immediate
  hemodynamic stability

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• Questions?

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Outpatient/ED
Inpatient
D-dimer
normal
Elevated
No PE
Chest CT
3rd gen scanner
Ist gen scanner
No PE PE
No PE PE
Ultrasound of leg veins
DVT No DVT
PAgram if continued clinical suspicion
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Unstable/shock
Hemodynamically stable/no shock
BNP BNP (RV on CT) Troponin (RV on CT)
ECHO
No RV dysfunction RV dysfunction
Fibrinolysis, embolectomy
anticoagulation
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PE
Risk stratify
Not high risk High risk
Anticoagulation fibronlysis/embolectomy
Heparin or heparin LMWH fondaparinux
Warfarin, 6 mos
Stop if due to trauma/surgery No signs of DVT
If idiopathic, continue lifetime
If thrombophilic, continue lifetime
If sxs DVT, doppler until clot resolved
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Diagnosisintegrated clinical decision rule

• Wells rule

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Chest XR

• Initial CxR always NORMAL.
• May show Collapse, consolidation, small pleural
  effusion, elevated diaphragm.
  
• Westermark sign Dilatation of pulmonary vessels
  proximal to embolism along with collapse of
  distal vessels, often with a sharp cut off.

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Chest XR

• Initial CxR always NORMAL.
• May show Collapse, consolidation, small pleural
  effusion, elevated diaphragm.
  
• Pleural based opacities with convex medial
  margins are also known as a Hampton's Hump

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Chest XRSigns of Infarction

• Consolidation
• Cavitation
• Pleural effusion (bloody in 65)
• SSA
• No air bronchograms
• Melting sign of healing
• Heals with linear scar

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DiagnosisV/Q Scan
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Pulmonary Angiogram

• Westermark sign Dilatation of pulmonary vessels
  proximal to embolism along with collapse of
  distal vessels, often with a sharp cut off.

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Prevention

• Only
• low-molecular-weight heparin
• graded compression stockings
• have been shown to reduce the incidence of
  pulmonary embolism in hospitalized patients.