challenging the conventional teachings of … the conventional ... and strongly stated...
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PulmonaryPulmonary Embolic Disease:Embolic Disease:Pulmonary Pulmonary Embolic Disease: Embolic Disease: Challenging the Conventional Challenging the Conventional
Wisdoms Wisdoms and Algorithmsand Algorithms
Marc V. Gosselin, MDMarc V. Gosselin, MD,,Oregon Health & Oregon Health &
Science UniversityScience UniversityScience UniversityScience University
Di l SDisclosure Statement
TheThe presenter(s)presenter(s) have no financialhave no financialThe The presenter(s) presenter(s) have no financial have no financial relationships with a commercial entity relationships with a commercial entity producing health care related productsproducing health care related productsproducing health care related products producing health care related products and/or services that would present a and/or services that would present a conflict conflict of of interest.interest.
Lecture ObjectivesLecture ObjectivesLecture ObjectivesLecture ObjectivesBriefly reviewBriefly review the pulmonarythe pulmonary eembolicmbolicBriefly review Briefly review the pulmonary the pulmonary eembolic mbolic mmultispecialty literatureultispecialty literature
OHSU study on 575 PCTA�sOHSU study on 575 PCTA�s
ClinicalClinical �conventional wisdoms�conventional wisdoms��Clinical Clinical conventional wisdomsconventional wisdoms examinedexamined
��Where all think alike, no one thinks Where all think alike, no one thinks very muchvery much �� �� Walter LippmannWalter Lippmannvery muchvery much. . Walter LippmannWalter Lippmann
Lecture FormatLecture Format
Virchow�s triad & The lung�s functionVirchow�s triad & The lung�s functionVirchow s triad & The lung s functionVirchow s triad & The lung s function
Risk factors for Thrombosis formationRisk factors for Thrombosis formationRisk factors for Thrombosis formationRisk factors for Thrombosis formation
Patient symptoms, signs, chest radiographPatient symptoms, signs, chest radiographPatient symptoms, signs, chest radiographPatient symptoms, signs, chest radiograph
Pulmonary CTA: Advantages & Pulmonary CTA: Advantages & ProblemsProblemsy gy g
Outcomes with versus without therapyOutcomes with versus without therapypypy
Qualifications?Qualifications?Qualifications?Qualifications?I am a I am a cardiopulmonary radiologistcardiopulmonary radiologist, not a , not a p y gp y ghematologist hematologist
NorNor do I even remotely enjoy looking over do I even remotely enjoy looking over the coagulation cascade diagramsthe coagulation cascade diagrams
Just an Curious physician whose Just an Curious physician whose observations over the last decade observations over the last decade have not have not matched matched much of the much of the commoncommon teachings teachings and and stronglystrongly stated recommendationsstated recommendations
Which one of these 3 Which one of these 3 radiographs isradiographs is mostmost
1radiographs is radiographs is most most
likely likely to have a to have a symptomaticsymptomatic PE?PE?symptomaticsymptomatic PE?PE?
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Challenging the Conventional Teachings ofPulmonary EmbolismMarc V. Gosselin, MD
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�Eminence� Based Medicine�Eminence� Based Medicine Concept 1Concept 1: Virchow�s : Virchow�s TriadTriadWhy Do We Clot?Why Do We Clot?Why Do We Clot? Why Do We Clot?
Vi h ' t i d i b d t l t 2Vi h ' t i d i b d t l t 2Virchow's triad is based on at least 2, Virchow's triad is based on at least 2, but likely but likely all 3 elements all 3 elements being presentbeing present Cotran et al
Concept 2Concept 2: The Study of Evolution: The Study of EvolutionConcept 2Concept 2: The Study of Evolution: The Study of Evolution
What is the function of the lung?What is the function of the lung?
It Is a FilterIt Is a FilterIt Is a FilterIt Is a Filter
The Liver & Lungs areThe Liver & Lungs areThe Liver & Lungs areThe Liver & Lungs areThe Organs That Have The Organs That Have A Dual Blood Supply.A Dual Blood Supply.pp ypp y
Why?Why?Why?Why?
37 37 yoyo male male -- Failed Suicide Attempt by Failed Suicide Attempt by Injecting Mercury: Injecting Mercury: The Lung is a FilterThe Lung is a Filter
Concept 3Concept 3: What Happens To The DVT?: What Happens To The DVT?
The venous endothelium The venous endothelium does not does not contain contain fibrinolytic enzymes to break up the clot?fibrinolytic enzymes to break up the clot?fibrinolytic enzymes to break up the clot?fibrinolytic enzymes to break up the clot?
Circulating fibrinolytic enzymes?Circulating fibrinolytic enzymes? WWherehere dodoCirculating fibrinolytic enzymes? Circulating fibrinolytic enzymes? WWhere here do do the the dislodged pieces dislodged pieces of clot goof clot go??
Neutrophils & Monocytes Neutrophils & Monocytes likely importantlikely important
Pulmonary capillary endothelium has a Pulmonary capillary endothelium has a complete complement complete complement of fibrinolytic of fibrinolytic enzymes to effectively break down enzymes to effectively break down clotclot
66 66 yoyo With Pancreatic With Pancreatic Cancer: DVTCancer: DVT --> PE> PECancer: DVT Cancer: DVT > PE> PEThe Lungs are O S f t N tOur Safety Net
: �Diamond Algorithm�g
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Example: RenalExample: Renal Dialysis PatientsDialysis PatientsExample: Renal Example: Renal Dialysis PatientsDialysis Patients
Fi t l i th f lti l ll PE�Fi t l i th f lti l ll PE�Fistula is the source of multiple small PE�s Fistula is the source of multiple small PE�s in these in these patientspatients
Do we treat the PEDo we treat the PE??
Risks of Risks of Therapy Therapy in these in these patients versus patients versus Risks of Withholding TherapyRisks of Withholding Therapy??
How about looking in the legs and staying How about looking in the legs and staying away from the lungs: Pandora�s boxaway from the lungs: Pandora�s box!!away from the lungs: Pandora s boxaway from the lungs: Pandora s box!!
Concept 4Concept 4: Incidence : Incidence of PEof PE>70% of PE are incidental >70% of PE are incidental (Pathology)(Pathology)
WW ftft fi d lti l lfi d lti l lWe We oftenoften find multiple or even large find multiple or even large incidentalincidental PE�s on PE�s on scans scans (1.5% outpatients, (1.5% outpatients, 66--9% inpatients 9% with malignancy and 24%9% inpatients 9% with malignancy and 24%66--9% inpatients, 9% with malignancy and 24% 9% inpatients, 9% with malignancy and 24% trauma patients)trauma patients)
55 9%9% positivepositive rate with ED patients andrate with ED patients and55--9% 9% positive positive rate with ED patients and rate with ED patients and 1010--15% for inpatients 15% for inpatients when when looking looking for for PEPEThe The diagnosis diagnosis is likely is likely considered considered too too quickly & with lower pretest probabilities quickly & with lower pretest probabilities ����We do have an �We do have an �easyeasy� test to look for it�� test to look for it�
Concept 5Concept 5: : Pulmonary Pulmonary Embolism in the Embolism in the UnitedUnited States; Evidence ofStates; Evidence of OverdiagnosisOverdiagnosisUnited United States; Evidence of States; Evidence of OverdiagnosisOverdiagnosis
ArchArch Intern Med.Intern Med. 2011;171(9):8312011;171(9):831--837837ArchArch Intern Med. Intern Med. 2011;171(9):8312011;171(9):831 837837
The introduction of CTPA was associated The introduction of CTPA was associated ith h i t t ithith h i t t ithwith changes consistent with with changes consistent with OverdiagnosisOverdiagnosis: : Rising Rising incidence, minimal incidence, minimal h i t lit dh i t lit d llchange in mortality, and change in mortality, and lower case lower case
fatalityfatality..
Mortality changed little because many of the extra emboli may not haveof the extra emboli may not have needed treatment at all.
Apparent incidence
MortalityFatal PE
per Case
When When ��conventional wisdomconventional wisdom� is � is substituted for substituted for clinical judgmentclinical judgment observationobservation and reasonand reasonclinical judgment, clinical judgment, observation observation and reason�and reason�
EmedicineEmedicine: Pulmonary Embolus : Pulmonary Embolus yy
�Symptoms that should provoke a �Symptoms that should provoke a i i f PE t i l d h t ii i f PE t i l d h t isuspicion of PE must include chest pain, suspicion of PE must include chest pain,
chest wall tenderness, back pain, shoulder chest wall tenderness, back pain, shoulder pain upper abdominal pain syncopepain upper abdominal pain syncopepain, upper abdominal pain, syncope, pain, upper abdominal pain, syncope, hemoptysis, shortness of breath, painful hemoptysis, shortness of breath, painful respiration new onset of wheezing anyrespiration new onset of wheezing anyrespiration, new onset of wheezing, any respiration, new onset of wheezing, any new cardiac arrhythmia, or new cardiac arrhythmia, or any other any other unexplained symptom referable to the unexplained symptom referable to the p y pp y pthoraxthorax.� .�
Prospective Study on the Incidence of Contrast-induced Nephropathy (CIN) After
Pulmonary CTAThe aim of this study was to define the risk ofThe aim of this study was to define the risk of CIN following CTPA (Followed for 45 days)
174 prospective patients underwent CTPA, which demonstrated acute PE in 12 (7%, 95% CI = 3% to 12%)
T t fi ti t d l d CIN (14% 95%Twenty-five patients developed CIN (14%, 95% CI = 10% to 20%) including one with acute PE
ACADEMIC EMERGENCY MEDICINE 2012; 19:618�625
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Alice Mitchell, MD et al: ACADEMIC EMERGENCY MEDICINE 2012; 19:618 625EMERGENCY MEDICINE 2012; 19:618�625
The development of CIN after CTPAThe development of CIN after CTPA significantly increased the risk (outcome) of severe renal failure or death from renalof severe renal failure or death from renal failure within 45 days (relative risk = 36, 95% CI = 3 to 384)95% CI 3 to 384)
No severe adverse outcomes were directly yattributable to complications of venous thromboembolism (VTE) or its treatment ( )
Concept 6Concept 6: �Sufficient� Risk Factors : �Sufficient� Risk Factors OHSU Study (OHSU Study (51 out of 5451 out of 54))OHSU Study (OHSU Study (51 out of 5451 out of 54))
Major Major traumatrauma
NeurologicalNeurological: Trauma: Trauma, surgery or , surgery or tumortumor
Major surgeryMajor surgery: especially cardiovascular, : especially cardiovascular, abdominal or abdominal or orthopedic (orthopedic (CC--section toosection too))
Active Active malignancymalignancy
HyperHyper--coagulation statecoagulation state -- Transient vs. Transient vs. Life Life long, Provoked vs. Idiopathic, long, Provoked vs. Idiopathic, Inflammatory State* (Sepsis?) Inflammatory State* (Sepsis?) **AteriosclerAterioscler ThrombThrombVascVasc Biol. 2008;28:387 Wakefield, Meyers & HenkeBiol. 2008;28:387 Wakefield, Meyers & Henke
Metastatic Colon Cancer:Metastatic Colon Cancer:6 Weeks S/P Chemo Rx6 Weeks S/P Chemo Rx -- No SymptomsNo Symptoms6 Weeks S/P Chemo Rx. 6 Weeks S/P Chemo Rx. -- No SymptomsNo Symptoms Restaging Restaging g gg g
HepatomaHepatomaAbdominalAbdominalAbdominal Abdominal
Pelvic CT ScanPelvic CT Scan
IncidentalIncidentalSaddle Saddle
E b li ithE b li ithEmboli with Emboli with RLL InfarctRLL InfarctRLL InfarctRLL Infarct
Hypercoagulability Hypercoagulability Seen In Immediate Seen In Immediate P tP t T S ttiT S ttiPostPost--Trauma SettingTrauma Setting
Schreiber et al Journal of TraumaSchreiber et al Journal of Trauma 20052005Schreiber et al. Journal of Trauma Schreiber et al. Journal of Trauma 20052005
Use of the Use of the Thrombelastograph analyzer Thrombelastograph analyzer g p yg p ygives comprehensive functional evaluation gives comprehensive functional evaluation of overall coagulation of overall coagulation statusstatusgg
�Activated� coagulation system highest in �Activated� coagulation system highest in fi 24 h ffi 24 h f i ji jfirst 24 hours of first 24 hours of injuryinjury
ProgressivelyProgressively decreases over next 3decreases over next 3 daysdaysProgressively Progressively decreases over next 3 decreases over next 3 daysdays
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35 year old female: Jumped off bridge35 year old female: Jumped off bridge
T7T7 compression fracture withcompression fracture with parapara--spinalspinalT7 T7 compression fracture with compression fracture with parapara spinal spinal hematoma.hematoma. Is there Anything Is there Anything else?else?
Concept 7Concept 7: �Trigger Events�: �Trigger Events�Component CausesComponent CausesComponent CausesComponent Causes
Physiological states where clotting occurs Physiological states where clotting occurs only in the presenceonly in the presence of other risk factorsof other risk factorsonly in the presence only in the presence of other risk factorsof other risk factors
Increasing AgeIncreasing Age
ImmobilizationImmobilization: Plane or Car ride : Plane or Car ride (or a (or a Radiologist onRadiologist on callcall))Radiologist on Radiologist on callcall))
Oral ContraceptivesOral Contraceptives: Very, very small : Very, very small riskrisk
PregnancyPregnancy: : 1/1000 1/1000 and and -- the majority have the majority have an underlying problem (67%)an underlying problem (67%)an underlying problem (67%)an underlying problem (67%)
Obesity?Obesity?
Case 8Case 8: Symptomatic PE : Symptomatic PE C EC E & Vit l& Vit lCommon Exam Common Exam & Vitals& Vitals
Acute onset of Shortness ofAcute onset of Shortness of breath (85%)breath (85%)Acute onset of Shortness of Acute onset of Shortness of breath (85%)breath (85%)
Tachycardia (70%) Tachycardia (70%) (on (on BB--blockerblocker?)?)y ( )y ( ) (( ))
Chest radiograph Chest radiograph oftenoften is is normal (80%)normal (80%)
Mild Mild -- moderate hypoxia on room moderate hypoxia on room air (65%)air (65%)
Differential: Asthma/small airways infection Differential: Asthma/small airways infection (Is there wheezing (Is there wheezing on on auscultationauscultation?)?)
Acute dyspnea and mild hypoxiaAcute dyspnea and mild hypoxia
Which one of these 3 Which one of these 3 radiographs isradiographs is mostmost
1radiographs is radiographs is most most
likely likely to have a to have a symptomaticsymptomatic PE?PE?symptomaticsymptomatic PE?PE?
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2
3
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Scanners are Getting Scanners are Getting Too Too GoodGood!!The Unexpected PE ProblemThe Unexpected PE Problem
WW t t tt t t ALLALL N thiN thiWe We can not treat can not treat everyoneeveryone ALL or ALL or NothingNothing
UnderstandingUnderstanding whichwhich subset ofsubset of peoplepeopleg g p p p p are most likely to benefit from therapy are most likely to benefit from therapy versus which are more likely to versus which are more likely to have an have an adverse affect adverse affect is our future is our future challengechallenge
First we need to releaseFirst we need to release somesomeFirst, we need to release First, we need to release some some conventional wisdoms conventional wisdoms & Eminence & Eminence based teachingbased teaching regarding PE�sregarding PE�sbased teaching based teaching regarding PE sregarding PE s
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Concept 9Concept 9: PE Mortality Exaggerated: PE Mortality Exaggeratedpp y ggy gg
19391939--1961 1961 work was work was retrospective, on retrospective, on ppinpatients & post surgical patientsinpatients & post surgical patients
Data skewed as to mortality (Data skewed as to mortality (1818 35%)35%)Data skewed as to mortality (Data skewed as to mortality (1818--35%), 35%), which is which is still often quoted still often quoted todaytoday
What is the natural What is the natural evolution evolution of VTE eventsof VTE events
1960�s sa1960�s sa aa briefbrief n mber ofn mber of1960�s saw 1960�s saw a a brief brief number of number of anticoagulation studies; most did anticoagulation studies; most did notnot use a use a Control GroupControl GroupControl GroupControl Group
What Subset of Patients is PE Fatal?What Subset of Patients is PE Fatal?Our Study: 2%Our Study: 2% SymptomaticSymptomatic PE were FatalPE were FatalOur Study: 2% Our Study: 2% SymptomaticSymptomatic PE were FatalPE were Fatal
Most deaths from pulmonary embolus occur inMost deaths from pulmonary embolus occur inMost deaths from pulmonary embolus occur in Most deaths from pulmonary embolus occur in patients with patients with ComorbidComorbid factors such as severely factors such as severely compromised cardiopulmonary function, cancer compromised cardiopulmonary function, cancer patients and increasingpatients and increasing ageagepatients and increasing patients and increasing ageage
Numerous cases of incidental PE or large Numerous cases of incidental PE or large clot clot burdenburden in normal cardiopulmonaryin normal cardiopulmonary functionfunctionburden burden in normal cardiopulmonary in normal cardiopulmonary functionfunction
Average ageAverage age--related death rates from PE is related death rates from PE is 2.32.3(Caucasian)(Caucasian) �� 6 06 0 (African American) per(African American) per(Caucasian) (Caucasian) 6.06.0 (African American) per (African American) per 100,000 100,000 persons persons
Lilienfeld. International Journal of Epidemiology 2000;29:465Lilienfeld. International Journal of Epidemiology 2000;29:465--469.469.
Nielson et al. 1994Nielson et al. 199487 ambulatory, relatively healthy patients 87 ambulatory, relatively healthy patients with DVT (with DVT (MostMost had asymptomatic PE)had asymptomatic PE)with DVT (with DVT (MostMost had asymptomatic PE)had asymptomatic PE)
46 randomly selected for therapy46 randomly selected for therapyy pyy py41 randomly received 41 randomly received nono therapytherapy
Result after 60 days: Result after 60 days: No difference in No difference in mortality, clot regression or progressionmortality, clot regression or progression1 patient died of PE, in the 1 patient died of PE, in the treatedtreated groupgroup
J Intern Med 1994;235:457J Intern Med 1994;235:457--461461
Anticoagulation for Acute Anticoagulation for Acute V Th b b li /PEV Th b b li /PEVenous Thromboembolism/PEVenous Thromboembolism/PE
The NNT WebsiteThe NNT WebsiteIn Summary, for those who got the anticoagulation:
100% saw no benefit0% were helped by being saved from death0.9% were harmed by a major bleeding event0.9% were harmed by dying due to the bleeding0.9% were harmed by dying due to the bleeding
In Other Words:None were helped (life saved, preventing PE)1 in 50-111 were harmed (major bleeding event)1 in >50 were harmed (death bleeding event)1 in >50 were harmed (death bleeding event)
Are we Over treating DVT/PE�s?
Concept Concept 1010: : How How Does Does IV Heparin IV Heparin Improve Symptoms so Quickly?Improve Symptoms so Quickly?Improve Symptoms so Quickly?Improve Symptoms so Quickly?
Within an Hour of starting IV Heparin;Within an Hour of starting IV Heparin;Within an Hour of starting IV Heparin; Within an Hour of starting IV Heparin; Symptoms Symptoms often often ImproveImprove
IV H i iIV H i i P l A t i lP l A t i lIV Heparin is a IV Heparin is a Pulmonary Arterial Pulmonary Arterial VasodilatorVasodilator -- Other Vasodilators found to Other Vasodilators found to h i il Eff t S t ti PEh i il Eff t S t ti PEhave a similar Effect on Symptomatic PEhave a similar Effect on Symptomatic PE
PulmonaryPulmonary VasoconstrictionVasoconstriction appears toappears toPulmonary Pulmonary Vasoconstriction Vasoconstriction appears to appears to be common with Symptomatic be common with Symptomatic patientspatientsCardiovascular Cardiovascular Research 48 (2000) 23Research 48 (2000) 23��3333
SummarySummary �� As of March 2014As of March 2014
Function of the lungsFunction of the lungsgg
Risk factors versus �Trigger� EventsRisk factors versus �Trigger� Events
Signs, Symptoms, Radiograph & DSigns, Symptoms, Radiograph & D--dimerdimer
CTA is CTA is notnot a screening study!a screening study!
Consider V/Q scan in young patients with Consider V/Q scan in young patients with normal lungsnormal lungs (AJR November 2009)(AJR November 2009)normal lungs normal lungs (AJR November 2009)(AJR November 2009)
