Acute Pulmonary Embolism

BY Dr- MOUSA ELSHAMLY

 PE refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat ) that originated elsewhere in the body

DEFINITIONS 

PEEpidemiologyPathophysiologyPrevention/Risk factorsScreeningDiagnosisTreatment

PEEpidemiology

Five million cases of venous thrombosis each year

10% of these will have a PE10% will dieCorrect diagnosis is made in only 10-30% of

casesUp to 60% of autopsies will show some

evidence of past PE

PEEpidemiology

90-95% of pulmonary emboli originate in the deep venous system of the lower extremities

Other rare locations include Uterine and prostatic veins Upper extremities Renal veins Right side of the heart

Risk FactorsCHFMalignancyObesityEstrogen/OCPPregnancy (esp post

partum)Lower ext injuryCoagulopathy

Venous StasisPrior DVTAge > 70Prolonged Bed RestSurgery requiring >

30 minutes general anesthesia

Orthopedic Surgery

Virchow’s TriadRudolf Virchow postulated more than a

century ago that a triad of factors predisposed to venous thrombosisLocal trauma to the vessel wallHypercoagulabilityStasis of blood flow

It is now felt that pts who suffer a PE have an underlying predisposition that remains silent until a acquired stressor occurs

Venous StasisAccumlation of activated procoagulants.

ImmobilizationInadequate cardiac pump.

Promotes thrombus formation.

Vessel Wall InjuryAcute or chronic injury to vessel

endothelium.Leads to activation of platelets and clotting

cascade.Promotes thrombus formation.

Vessel Injury

Platelet Adhesion

Aggregation

Alternations in CoagulationIncrease in procoagulant factors.

By trauma to vascular wall or extravascular tissues.

Releases tissue thromboplastin and phospholipid.

Leads to formation of prothrombin activator.Prothrombin Thrombin

Alterations in CoagulationDecrease in anticoagulant factors.

ThrombomodulinAntithrombin IIIHeparinAlpha2-MarcoglobulinPlasmin

Leads to hypercoagulable state by formation of thrombin.

Thrombosis FormationPlatelet nidus at site of injury.Growth by aggregation of platelets and fibrin.Activation of clotting cascade.Larger growth to a red fibrin thrombus.Thrombus fractures and embolizes to other

areas of the body.

Predisposing Factors or Diseases for Development of PTEHypercoagulable state

Nephrotic syndromeImmobilizationAmyloidosisEarly DICHyperadrenocorticism

Capillary fragilityActivation of clotting cascade.

Predisposing Factors or Diseases for Development of PTEHypercoagulable stateCapillary fragility

Diabetes MellitusImmune–mediated hemolyitc anemiaSepsisHyperadrenocorticism

Activation of clotting cascade.

Factor V Leiden mutation Protein C deficiency Protein S deficiency Antithrombin deficiency Prothrombin gene mutation A20210 Anticardiolipin antibodies Lupus anticoagulant Hyperhomocystinemia

Predisposing Factors or Diseases for Development of PTEHypercoagulable stateCapillary fragilityActivation of clotting cascade.

SepsisPneumonia/pyothoraxHeartworm diseaseSurgeryBacterial endocarditisNeoplasia

Factor V LeidenMost frequent inherited predisposition to

hypercoagulabilityResistance to activated Protein C

Single point mutation (Factor V Leiden) Single nucleotide substitution of glutamine for

arginine Frequency is about 3% in healthy American male .

PEWhen venous emboli become dislodged from

their site of origin, they embolize to the pulmonary arterial circulation or, paradoxically to the arterial circulation through a patent foramen ovaleAbout 50% of pts with pelvic or proximal leg

deep venous thrombosis have PEIsolated calf or upper extremity venous

thrombosis pose a lower risk for PE

Pathophysiology Increased pulmonary vascular resistanceImpaired gas exchange Alveolar hyperventilationIncreased airway resistanceDecreased pulmonary compliance

Consequences of PTERespiratory.

Increased alveolar dead space.Hyperventilation.Hypoxemia.Ventilation/perfusion inequality.Intrapulmonary shunts.

Normal Alveolus

Increased Alveolar Dead Space

HypoxemiaResults from ventilation-perfusion inequality, physiologic shunting and increased dead space.

Intrapulmonary ShuntsBlood that has not been to areas of ventilated

lung and enters systemic circulation without gas exchange taking place.

Poorly oxygenated blood enters the arterial system lowering the PaO2.

Not responsive to oxygen therapy.

Ventilation/Perfusion InequalityV/Q inequality occurs when distribution of

blood is altered to the alveoli.O2 increase in the alveoli and CO2 decreases.

Hemodynamic ChangesIncrease in pulmonary vascular resistance.Increased afterload to the right heart.Can lead to circulatory collapse and shock.

Right Ventricular DysfunctionProgressive right heart failure is the usual

immediate cause of death from PEAs pulmonary vascular resistance increases,

right ventricular wall tension rises and perpetuates further right ventricle dilation and dysfunction

Interventricular septum bulges into and compresses the normal left ventricle

Clinical SyndromesPts with massive PE present with systemic

arterial hypotension and evidence of peripheral thrombosis

Pts with moderate PE will have right ventricular hypokinesis on echocardiogram but normal systemic arterial pressure

Pts with small to moderate PE have both normal right heart function and normal systemic arterial pressure

Well’s CriteriaClinical Signs and Symptoms of DVT?(Calf tenderness, swelling >3cm, errythema, pitting edema affected leg only)

+3

PE Is #1 Diagnosis, or Equally Likely +3

Heart Rate > 100 +1.5

Immobilization at least 3 days, or Surgery in the Previous 4 weeks

+1.5

Previous, objectively diagnosed PE or DVT? +1.5

Hemoptysis +1

Malignancy w/ Rx within 6 mo, or palliative? +1

>6: High Risk2 to 6: Moderate Risk2 or less: LowAdapted with permission from Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED d-dimer.Thromb Haemost 2000;83:416-20.

DiagnosisH&PAlways ask about prior DVT, or PE

Family History of thromboembolismDyspnea is the most frequent symptom of PETachypnea is the most frequent physical

findingDyspnea, syncope, hypotension, or cyanosis

suggest a massive PEPleuritic CP, cough, or hemoptysis

Signs of P.E.TachypneaRalesTachycardiaHypoxiaS4Accentuated pulmonic component of

S2Fever: T <102 F

Signs in Massive P.E.“Massive PE”: hemodynamic instability with

SBP <90 or a drop in baseline SBP by >/=40mmHg for more then 30 min

Signs as before PLUS:Acute right heart failure

Elevated J.V.P. Right-sided S3 Parasternal lift

P.E. & Leg SymptomsMost patients with P.E. do not have leg

symptoms at time of diagnosisPatients with leg symptoms may have

asymptomatic P.E.

Differential Diagnosis

USA, MIPneumoniaCHFAsthmaCostochondritis, Rib Fx,PneumothoraxPE can coexist with other illnesses!!

Physical Signs & Symptoms· Dyspnea 73% · Pleuritc Pain 66% · Cough 43% · Leg Swelling 33% · Leg Pain 30% · Hemoptysis 15% · Palpitations 12% · Wheezing 10% · Angina-Like pain 5%

DiagnosisSerum Studies

D-dimer Elevated in more than 90% of pts with PE Reflects breakdown of plasmin and endogenous

thrombolysis Not specific: Can also be elevated in MI, sepsis, or

almost any systemic illness Negative predictive value

ABG-contrary to classic teaching, arterial blood gases lack diagnostic utility for PE

DiagnosisCXR

Usually reveals a non specific abnormality. 14% normal

Classic abnormalities include: Westermark’s Sign - focal oligemia Hampton’s Hump - wedge shaped density

Enlarged Right Descending Pulmonary Artery (Palla’s sign)

Chest X-ray Eponyms of PEWestermark's sign

A dilation of the pulmonary vessels proximal to the embolism along with collapse of distal vessels, sometimes with a sharp cutoff.

Hampton’s Hump

A triangular or rounded pleural-based infiltrate with the apex toward the hilum, usually located adjacent to the hilum.

43

PE

Hamptons Hump

PE

Westermark’s Sign

Radiographic Eponyms- Hampton’s Hump, Westermark’s Sign

46

Westermark’s Sign

Hampton’s Hump

PE which appears likea mass.

PE with effusionand elevated diaphragm

How About This???Westermark's Sign: an abrupt tapering of a vessel caused by pulmonary thromboembolic obstruction. This CXR shows enlargement of the left hilum accompanied by left lung hyperlucency, indicating oligemia (Westermark's sign).

What’s This???

Hampton’s Hump

Lab & Radiologic Findings in P.E.ABGBNPCardiac Enzymes: TroponinD-dimerEKGCXRUltrasoundV/Q ScanAngiography

Lab Findings in P.E.(ABG)ABG:

HypoxemiaHypocapnia (low CO2)Respiratory AlkalosisMassive PE: hypercapnia, mix resp and

metabolic acidosis (inc lactic acid)Patients with RA pulse ox readings <95% are

at increased risk of in-hospital complications, resp failure, cardiogenic shock, death

Lab Findings in P.E. (BNP)BNP (beta natruretic peptide)

Insensitive testPatient’s with PE have higher levels than pts

without, but not ALL patients with PE have high BNP

Good prognostic value measure: if BNP >90 associated with adverse clinical outcomes (death, CPR, mechanical vent, pressure support, thrombolysis, embolectomy)

Lab Findings in P.E. (Troponin)Troponin

High in 30-50% of pts with mod to large PEPrognostic value if combined pro-NT BNP

Trop I >0.07 + NT-proBNP >600 = high 40 day mortality

Lab Findings in P.E. (D-dimer)D-dimer:

Degredation product of fibrin>500 is abnormalSensitivity: High, 95% of PE pts will be positiveSpecificity: LowNegative Predictive Value: Excellent

Lab Findings in P.E. (cont’d)EKG

2 Most Common finding on EKG: Nonspecific ST-segment and T-wave changes Sinus Tachycardia

Historical abnormality suggestive of PE S1Q3T3 Right ventricular strain New incomplete RBBB

S1Q3T3!!!

RAD

Right Atrial Enlargement

Venous UltrasonographyRelies on loss of vein compressibility as

the primary criterionAbout 1/3 of pts will have no imaging

evidence of DVT Clot may have already embolized Clot present in the pelvic veins (U/S usually

inadequate)Workup for PE should continue even if

dopplers (-) in a pt in which you have a high clinical suspicion

V/Q ScanHistorically, the principal imaging test for the diagnosis of PEA perfusion defect indicates absent or

decreased blood flowVentilation scan obtained with radiolabeled

gasesA high probability scan is defined as two or

more segmental perfusion defects in presence of nl ventilation scan

V/Q ScanUseful if the results are normal or near

normal, or if there is a high probability for PEAs many as 40% of pts with high clinical

suspicion for PE and low probability scans have a PE on angiogram

High Probability V/Q Scan

Pulmonary AngiogramMost specific test available for diagnosis of

PE Can detect emboli as small as 1-2 mmMost useful when the clinical likelihood of PE

differs substantially from the lung scan result or when the lung scan is intermediate probability

Pulmonary Angiogram

PE on pulmonary angiogram

EchocardiogramUseful for rapid triage of ptsAssess right and left ventricular functionDiagnostic of PE if hemodynamics by echo are

consitent with clinical

Spiral CT ScanIdentifies proximal PE (which are the ones

usually hemodynamically important)Not as accurate with peripheral PE

CT revealing pulmonary infarct

CT revealing emboli in pulmonary artery.

DiagnosisSpiral CT/ Multislice

Ascending Aorta

Lt Pulmonary Artery

Main Pulmonary Artery

Rt Pulmonary Artery

Descending Aorta

Thrombus

Bilateral PE

SPIRAL CT SCAN

Criteria for PE extension:

obstruction index according to the scoring system of Qanadli

∑ (n · d)

n = number of segmental branches

d = obstruction degree (1 if partial 2 if complete)

2-slice CT

19922 x 2.7 mm

25 sec4-slice CT

1998

4 x 1 mm25 sec

64-slice2004

64 x 0.625 mm

4 sec

16-slice CT

2002

16 x 0.75 mm

10 sec

PE at MDCT

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

Clinical probability assessment

Low or intermediate High (≈ 30%)

Diagnosis of PE in stable patients

D-dimer

Normal Elevated

PE excluded (≈30%)

Multi-detector CT

Positive for PE No PE

Treat

Echocardiography

RVD present No RVD

Diagnosis of PE in un-stable patients

Treat & stabilize

Multidetector CT Search for alternative diagnosis

TreatmentBegin treatment with either

unfractionated heparin or LMWH, then switch to warfarin (Prevents additional thrombus formation and permits endogenous fibrinolytic mechanisms to lyse clot that has already been formed, Does NOT directly dissolve thrombus that already exists)

Warfarin for atleast 3 months, INR 2-3

TreatmentPain ReliefSupplemental OxygenDobutamine for pts with right heart failure

and cardiogenic shockVolume loading is not advised because

increased right ventricular dilation can lead to further reductions in left ventricular outflow

AnticoagulationStart during resuscitation phase itselfIf suspicion high, start emperic

anticoagulation Evaluate patient for absolute

contraindication (i.e.: active bleeding)

Anticoagulation (cont’d)HEPARIN:

Lovenox: if hemodynamically stable, no renal function 1mg/kg BID OR 1.5mg/kg QDay

Heparin gtt: if hypotension, renal failure 80units/kg bolus then 18units/kg infusion Goal PTT1.5 to 2.5 times the upper limit of normal

COUMADIN:Start once acute anticoagulation achievedStart with 5mg PO qday OR 10mg PO q day If start with 10mg then achieve therapeutic INR 1.4

days soonerComplications and morbidity no different in 5mg or

10mg start Goal INR 2 to 3

Duration of Anticoagulation for DVT or PE*

Event Duration Strength of Recommendation

First Time event of Reversible cause (surgery/trauma)

At least 3 mos A

First episode of idiopathic VTE

At least 6 mos A

Recurrent idiopathic VTE or continuing risk factor (e.g., thrombophilia, cancer)

At least 12 mos B

Symptomatic isolated calf-vein thrombosis

6 to 12 weeks A

*From American College of Chest Physicians

ThrombolysisConsidered once P.E. diagnosedIf chosen, hold anticoagulation during

thrombolysis infusion, then resumedAssociated with higher incidence of major

hemorrhage Indications: persistent hypotension,

severe hypoxemia, large perfusion defecs, right ventricular dysfunction, free floating right ventricular thrombus, paten foramen ovale

Activase or streptokinase

IVC FilterIndication:

Absolute contraindication to anticoagulation (i.e. active bleeding)

Recurrent PE during adequate anticoagulation

Complication of anticoagulation (severe bleeding)

Also: Pts with poor cardiopulmonary reserveRecurrent P.E. will be fatalPatient’s who have had embolectomyProphylaxis against P.E. in select patients

(malignancy)

Embolectomy Surgical or catheterIndication:

Those who present severe enough to warrant thrombolysis

In those where thrombolysis is contraindicated or fails

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 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.

ConclusionPE is often a misdiagnosed clinical disorder.Rapid identification and appropriate

treatment may often prevent unnecessary morbidity and mortality.