Acute Pulmonary EmbolismPeter DeLong MDPulmonary and Critical Care MedicineDHMC

December 15, 2008

What we will coverDefinitionEpidemiologyRisk factorsDiagnosisPresentationtestsalgorithmTreatmentRisk stratificationDuration of therapy

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

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

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.

EpidemiologyMortality is 15% within 3 months after occurrence

In 25% of PE, the initial manifestation is death

Risk FactorsVirchows triadStasisVenous injury/endothelial damageHypercoagulability

Most patients have several of these

Risk FactorsInheritedFactor V leidenProthrombin gene mutationLow protein C, protein S, antithrombin IIIFamily history of VTE

Acquired AgeSmokingObesityimmobilityMalignancyAPL Ab syndrome [venous and arterial]Hyperhomocysteinemia (can be acquired) [venous and arterial]OCPs or hormone replacementAtherosclerosisTrauma, surgery, hospitalizationInfectionLong haul air travelElectronic leads, indwelling catheters

Who gets Evaluated For Thrombophilia?Patients in whom there is a high clinical suspicion for underlying disorderPE not associated with acquired risk factorCan be after first event!Family history

Initial evaluation directed towards most common

Most commonFactor V LeidenProthrombin gene mutationAPL Ab syndromeHyperhomocysteinemia

Less commonProtein C&S deficiency, ATIII deficiency

Diagnosis

pathophysiology is complex and results in variable clinical presentation

Acute PE: PathophysiologyGas exchange abnormalitiesRight to left shuntLeads toHypoxemiaIncreased a-A gradientV/Q MMIncreased dead spaceRespiratory alkalosis from hyperventilationOften a sign of increased dead space and impaired minute ventilationmay suggest massive PE

Acute PE: PathophysiologyHemodynamic abnormalitiesDepends on size of embolusIncreased vascular resistance/RV afterloadMay cause RV dilation, hypokinesis, tricuspid regurgitation, FAILUREInterventricular flattening, impaired LV fillingIncreased wall stress and ischemia

DiagnosisSymptoms and SignsSymptomsDyspneaChest pain (pleuritic) ApprehensionCoughHemoptysisSyncopePalpitationsWheezingLeg painLeg swelling

SignsTachycardia TachypneahypoxemiaAccentuated S2 FeverDiaphoresisSigns of DVTCardiac murmurJugular venous distentionCyanosisHypotension

DiagnosisLaboratory EvaluationD-dimerNon specific measure of fibrinolysisMeasured by ELISAHigh 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

DiagnosisChest XRCXRMost often normalMay show collapse, consolidation, small pleural effusion, elevated diaphragm.

Uncommon findings include Westermarks signDilation of vessels proximal to embolismHamptons humpPleural based opacities with convex medial margins

DiagnosisECGECG may show Complete or incomplete RBBT wave inversions anteriorly, S1Q3T3The latter is very overrated..

DiagnosisVQ Scan PerfusionVentilationMismatch

DiagnosisV/Q scansOld standard

Currently reserved for Renal impairmentIV contrast allergiesPregnancyChronic PE (controversial)

DiagnosisCT scan New StandardData suggests CT is as accurate as invasive angiography (gold standard)

Negative predictive value of 99%Quiroz et al, JAMA 2005

DiagnosisSpiral CT/ Multislice Ascending AortaLt Pulmonary ArteryMain Pulmonary ArteryRt Pulmonary ArteryDescending AortaThrombus

Pulmonary Angiogram

DiagnosisMRI MR AngiogramVery good to visualize the blood flow.Almost similar to invasive angiogram

A word about test InterpretationBayes theoremInterpretation 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..

Another word about test InterpretationAs 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

Diagnostic algorithmOutpatient/EDInpatientD-dimernormalElevatedNo PEChest CT3rd gen scannerIst gen scannerNo PEPENo PEPEUltrasound of leg veinsDVTNo DVTPAgram if continued clinical suspicion

You have diagnosed a PEWhat now?

(heparin, then.)

Risk stratification

Essentially based on hemodynamic stabilityElevated biomarkers troponins, BNP should prompt ECHO Some argue for routine ECHO

ECHO for Risk StratificationInsensitive 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)

Risk stratification algorithmHemodynamically stable/no shockUnstable/shockFibrinolysis, embolectomyBNPBNP(RV on CT)Troponintroponin(RV on CT)ECHONo RV dysfunctionRV dysfunctionanticoagulation

TreatmentAnticoagulationMainstay of therapyUnfractionated heparin for PTT 60-80 secsPreferred in pts undergoing further therapy as it can be reversedWeight based nomograms are effective for initiating therapyLMWHMore predictable responseNo dose adjustmentsRenally cleared. Some some pts need adjustmentsKidney dz, pregnancy, massive obesity may need anti factor Xa monitoringUsefulness questioned as correlation with antithrombotic effect not clear

TreatmentWarfarinVitamin K antagonist

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

TreatmentNewer agentsFondaparinuxSynthetic pentasaccharide with anti- Xa activity

Once daily

No adjustments

No risk of HIT

Treatment ComplicationsHITBoth UFH and LMWH can cause HITLMWH much less soHIT from IgG against heparin platelet factor IV complexScreen when platelets drop by >50%if suspected, stop all heparinStart direct thrombin inhibitor like lepirudin or argatroban

TreatmentThrombolyticsT-PA (alteplase) FDA approved for PE100 mg infused over 2 hrs

no difference in mortality or recurrent PE at 90 days compared to UFH

TreatmentSurgical embolectomy requires a specialized centerCan be safeCan be effectiveSmall published numbers

Catheter directed embolectomyEmerging as effective therapy when fibrinolysis cannot be usedCan be performed up to 5 days after event

TreatmentDuration algorithmPERisk stratifyNot high riskHigh riskAnticoagulationfibronlysis/embolectomyHeparinorheparinLMWHfondaparinuxWarfarin, 6 mosStop if due to trauma/surgeryNo signs of DVTIf idiopathic, continue lifetimeIf thrombophilic, continue lifetimeIf sxs DVT, doppler until clot resolved

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; 126:401s

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

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.

Recommendations LMW heparin may be used in place of unfractionated heparin.

Dosing requirements are individualized for each product.

Recommendations Duration of therapyFirst 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.

RecommendationsIVC 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

TreatmentIVC filterWith filter 5% risk of recurrent pulmonary embolus, especially after 6 mos. complication of leg swelling can occur.

anticoagulation is continued if possible.

Summary

Heparanize (or anticoagulate somehow)

Think about pre-test probability

Think about risk stratification beyond immediate hemodynamic stability

Questions?

Outpatient/EDInpatientD-dimernormalElevatedNo PEChest CT3rd gen scannerIst gen scannerNo PEPENo PEPEUltrasound of leg veinsDVTNo DVTPAgram if continued clinical suspicion

Hemodynamically stable/no shockUnstable/shockFibrinolysis, embolectomyBNPBNP(RV on CT)Troponin(RV on CT)ECHONo RV dysfunctionRV dysfunctionanticoagulation

PERisk stratifyNot high riskHigh riskAnticoagulationfibronlysis/embolectomyHeparinorheparinLMWHfondaparinuxWarfarin, 6 mosStop if due to trauma/surgeryNo signs of DVTIf idiopathic, continue lifetimeIf thrombophilic, continue lifetimeIf sxs DVT, doppler until clot resolved

Diagnosisintegrated clinical decision ruleWells rule

Chest XRInitial 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.

Chest XRInitial 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

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

DiagnosisV/Q Scan

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

PreventionOnly

low-molecular-weight heparin graded compression stockings

have been shown to reduce the incidence of pulmonary embolism in hospitalized patients.

Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*Intro: Pulmonary EmbolusTraining Week April 2005*