PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS

James Huffman11.13.2008Thanks to Dr. Gil Curry, Dr. Nadim Lalani

Outline Epidemiology / Pathophysiology DVT

Anatomy Clinical Presentation Diagnostic Approach

Pre-test probability Labs Imaging

Real-Life Algorithm Treatment

Outline PE

Clinical Presentation Diagnostic Approach

Pre-test probability Labs EKG Imaging

X-ray, CT, MR Real-Life Algorithm

Focus: the bottom line

Epidemiology

VTE is a ‘spectrum’ : Simple superficial thrombophlebitis to fatal PE

Est incidence : 100 /100 000 1/3 of cases are PE Increases dramatically with age (sharp increase after the age of 45)

DVT: Only 1/3 of pts investigated for DVT have it “silent” PE present in 40-60% of pts with DVT In asymptomatic pts w/ proven DVT, up to 1/3 will have

undiagnosed PE With treatment 50% have residual clot up to 1y Without treatment 50% recurrence w/ in 3 mo

Epidemiology

PE: 10% fatal w/ in 1st Hour 75% pt w/ PE have DVT (2/3 proximal vein) Classic presentations are less common than atypicals

and asymptomatic VTE is common 20% have “pleuritic CP” in ED 5-10% PE have shock as initial presentation

Despite treatment, kills 1-8%

Complications: postphlebitic syndrome [40%] pulmonary HTN [4%]

Pathophysiology of Thrombosis

Fibrinogen is converted to fibrin in response to vasc. Injury and inflammation

Fibrin is 1° structural framework of embolized clots and excessive fibrin deposition provides the nidus of VTE

VTE is the end-product of imbalanced clot formation and breakdown

What promotes this imbalance of fibrin deposition and removal?

Virchow’s TriadWhite, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003.

1. Injury to the vascular endothelium

2. Alterations in blood flow3. Hypercoagulability

Anything else associated with imbalanced clot formation?

Age – likely through a combination of the above mechanisms

Coagulation Cascade

Coagulation Cascade

PT/INRWarfarin

PTTHeparin

Anatomy

Depth Deep Superficial*

Proximal Popliteal v. or

higher Distal

*Superficial femoral vein is a member of the deep group

Case 1 55♀: Referred to ED for pain, redness

and swelling of right calf WIC today: Sent to ED with note:

History Started 3/7 ago Denies previous DVT Has been on IV combo chemotherapy for ovarian Ca

diagnosed six months ago (extensive pelvic lymph node involvement – which has improved as per recent U/S)

Fell day before this started and “twisted her knee”

All this is good – what are your main goals with history? Determine pre-test probability of DVT Look for other causes

DVT: History is Risk AssessmentHypercoagulability: Autoimmune Disease and Immune Deficiency

Not just SLE! Remember IBD Cancer Chemotherapy: especially breast CA Coagulopathy:

Factor V Leiden. Present in 7% pop = 50% Protein C, protein S & antithrombin III deficiency = 15% DVT. Resistance to aPC Lupus anticoagulant Prothrombin G20210A antiphospholipid antibodies others

DVT: History is Risk AssessmentStasis: Immobility: Not just surgery – remember other conditions

(oldies!) Heart Disease (AMI & CHF): independent of bedrest Travel ?Duration / proximity? Hyperlipiedmia PolycythemiaEndothelial Injury: Stroke Vascular surgery PVDOthers: Age, race, prior DVT, blood types, tissue antigens,

homocysteine

Case 1 Continued

When you examine her what do you expect to find?

P/E: Generalised tenderness to her calf Exquisite pain in popliteal fossa along vein Edema, erythema and warmth Swollen 3.5 cm Homan’s Sign +

What do you think of this?

Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)

Classically: Leg tenderness , Homan’s Sign Swelling Pitting edema Dilated superficial veins Erythema Calor

Neither sensitive nor specific OR’s between 2- 4

Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)

DVT: H&P Bottom Line Neither is sensitive or specific

i.e. you can’t rule-in or rule-out a DVT

Use them to decide pre-test probability

Clinical Prediction Rule: EvolutionLandefeld et. Al 1990

354 pts suspected of DVT that underwent venography

5 clinical predictors identified: 1 or more 95% Sens [92-100] 20% spec

[15-25] Swelling above the knee Swelling below the knee Recent immobility Fever Cancer

Absence of all only 5% DVT

Pretest ProbabilityWells, P., et al. 1995. Accuracy of Clinical Assessment of Deep Vein Thrombosis. Lancet:345; 1326-30

First Wells Criteria Based on

literature review and clinical experience of investigators

Study showed value in stratifying pretest probability with respect to eliminating need for repeat u/s

Pretest ProbabilityWells, P, et al. 1997. Lancet:350;1795.

Revised Wells score through logistic regression analysis Prospectively validated using same treatment algorithm (next

slide) 593 patients from two Canadian tertiary care centres Score ≥ 3 (high risk), 1 or 2 (moderate risk), <1 (low risk)

Pretest Probability Wells, P, et al. 1997. Lancet:350;1795.

593 pts w/ suspect DVT Stratified low, mod, high risk compression U/S /veno 3% of Low risk, 17% of moderate risk, 75% of high risk pts

had DVT Concluded that Clinical probability + U/S safe [0.6% missed]

Pretest Probability

This algorithm re-presented in JAMA rational clinical examination seriesAnand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this

patient have deep vein thrombosis? JAMA. 1998 Dec 2;280(21):1828-9.

What’s missing?

The N’Dimer!

D-Dimer Testing

U/S not a perfect test Degradation product of fibrin Non-specific

PPV bad +ve: surgery, trauma,

hemorrhage, CA, pregnancy, sepsis, >80 yrs old

Sensitivity variable Need Pre-test probability to

r/o DVT

Assay

Sensitivity Specificity

Whole blood agglutination (SimpliRED)

80-85% 70-90%

Latex agglutination

90-95% 40-90%

Rapid ELISA 95-100% 30-60%

CHR uses

D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35

RCT (N=1096)

D-Dimer vs no D-Dimer

DVT Likely = Wells ≥ 2

# of U/S per pt decreased in D-dimer group (0.78 vs 1.34)

D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35

“Modified” Wells Criteria Used SimpliRED and IL-Test

assays (less sens) Conclusion:

Clinical prediction rule + D-Dimer can safely r/o DVT

Case 1 continued Pretest probability?

Active cancer (1) Localized tenderness (1) Calf swelling (1) Edema (1) Other Diagnosis? Compression by pelvic nodes? (Doesn’t

matter – score would still be “not low risk”) What about the D-Dimer – Would you order it?

Doesn’t matter – it was sent already Level positive at 1.77C Both CMAJ and Well’s protocols would have you order it

anyway (we’ll discuss)

So she gets either 4 or 2 points = DVT likely

What next Einstein?

UltrasoundAmerican Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66

Well studied Widely available Proven accurate for Dx symptomatic prox DVT Like CT/PE provides other Dx: hematomas, baker’s cysts,

lymphad, aneurism, thrombophlebitis and abscess Has been advanced by the combination of compression

and doppler

Bottom line: U/S is the test of choice for DVT

Duplex UltrasoundStork, A. 2005. Calgarian J of PPT Slides. 1(1) pp1

Two partsi) Compression

- Tech applies pressure- clot not compressible

ii) Doppler (B mode) Shows blood flow

Ultrasound Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

EDE

Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32. Retrospective analysis 1994 EPs trained to perform colour doppler US (20-30

studies each) 100% sensitive, 75% specific for acute DVT

2 false-positives were in chronic DVT

Frazee BW, et al. J Emerg Med 2001;20(2):107–12. Prospectively demonstrated 95.7% NPV for EP

performed LCUS

Naughty by Nature - “Feel me flow”

EDE – ED Flow Blaivas M, et al. Acad Emerg Med. 2000;7(2):120–6.

Median exam time of 3m 28s 98% correlation with vascular lab-performed studies on same pts

Theodoro D, et al. Am J Emerg Med. 2004;22(3):197–200. 125m reduction in time to pt disposition with EP-performed US Kappa = 0.9, 99% agreement (154/156 cases)

Jang T, et al. Acad Emerg Med. 2004;11(3):319–22. 8 emerg residents (4 PGY-1, 2 PGY-2, 2 PGY-3) 1h focused training (didactic and practice on 2 healthy volunteers) SN = 100%, SP = 91.8%, avg scan time = 11.7min (self-reported) 4 false-positives (chronic DVT), 0 false-negatives

Ultrasound: Limitations

Obese, ++edema, immobilsation devices (x-fix) Doesn’t see isolated thrombi in iliac or superficial femoral veins

within abductor canal MRI better Pelvic masses may cause noncompressibility in absence of

thrombus false +’ve Most importantly: U/S doesn’t return to normal after acute DVT Therefore use impedance plethysmography for recurrent DVT

U/S - 60-70% of studies return to normal at one year IP – 90% return to normal within a year

CT-VenographyGoodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6

PIOPED II Data 711 pts with CT-V and sonography Results:

95.5% concordance for dx or exclusion of proximal DVT

Kappa = 0.809 Simlar results across all subgroups

(asymptomatic, symptomatic, previous DVT)

Bottom Line Thus Far?

1. Hx/PE help us decide pretest probability (Wells)

2. We add in a sensitive Test (D-Dimer)3. And a sensitive confirmatory test (U/S)

‘Cause Stone Cold says so!

Real-Life ApproachScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

Or…the 1620h approachFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

CHR Approach

The next 4 slides describe the current Calgary Health Region approach

Not many people use this as it is a bit outdated but I’ve kept the slides here for your interest

Wells Criteria for Probability of DVT

Clinical Hx/Sign Criteria Points

1. Malignancy receiving active treatment for cancer

OR have received treatment for cancer in past 6 mo.

OR are receiving palliative care for cancer

1.0

2. Limb immobilization Paralysis

OR Paresis

OR Recent casting of lower extremity

1.0

3. Patient immobilization bedrest (except access to BR) > 3 days

OR surgery in previous 4 weeks

1.0

4. Localized tenderness Along distribution of deep venous system 1.0

5. Entire leg swollen 1.0

6. Calf swelling >3cm when compared with asymptomatic leg

Measured 10cm below the tibial tuberosity

1.0

7. Pitting edema Greater in the symptomatic leg 1.0

8. Collateral superficial veins dilated

Non-varicose veins 1.0

9. Alternative Dx as likely or more likely than that of DVT

No specific criteria – use Hx, Physical, CXR, EKG, and labs to decide

-2.0

LOW PROB< 0 points

MOD PROB1 or 2 points

HIGH PROB>3 points

D-Dimer

Neg Positive

STOP CUS legs

Normal DVT

TREAT

LOW PROBABILITY DVT

STOP

D-Dimer

Neg Positive

STOP CUS legs

Normal DVT

TREAT

MODERATE PROBABILITY DVT

CUS legin 1 week

Normal Positive

STOP TREAT

CUS legs

Normal DVT

TREAT

HIGH PROBABILITY DVT

Venography

Normal Positive

STOP TREAT

Case 1 Continued Okay back to it… U/S shows popliteal vein DVT Management Doctor?

Treatment Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

Goals: Short Term:

Prevent extension of thrombus and/or PE Long Term:

Prevent recurrent events Prevent complications

Chronic Venous Insufficiency Pain Vericose Veins Ulcers

Postphlebitc syndrome Pulmonary Hypertension

Medical ManagementRosen’s Emergency Medicine 6th Edition

Used to be admit start UFH and Warfarin Now know that LMWH equally efficacious and ?more

safe Many centres now go for either tinzaparin (175 U/kg OD) or

Enoxaparin (1mg/kg BID) UFH (80U/kg IV bolus then 18U/kg/h infusion)

Unless contraindications, can start AC in ED [Warfarin (10mg) Required for at least 3 months] not all

cases Goal INR is usually 2-3

Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolismVan Dongen C. Cochrane Review 2005

22 studies (n = 8867)

Thrombotic complications (18 trials)

LMWH = 151/4181 (3.6%)

UFH 211/3941 (5.4%) OR 0.68; (0.55 to 0.84

Thrombus size was reduced (12 trials)

LMWH= 53% UFH 45% OR 0.69 (0.59 to 0.81)

Major hemorrhages (19 trials)

LMWH = 41/3500 (1.2%) UFH 73/3624 (2.0%) OR 0.57 (0.39 to 0.83)

Mortality (18 trials) LMWH 187/4193 (4.5%) UFH 233/3861 (6.0%) OR 0.76 (0.62 to 0.92)

BID dosing ? Better CI for OR crossed 0

Aric 2005

Case 1 Continued

Pt started on Enoxaparin Arranged to see her oncologist and a

hematologist as out-patient 2 days later

Discharge Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

Outpatient treatment is safe and effective in a wide variety of patients

Admission may be required if: Co-morbidities:

Renal failure, high bleeding risk Extensive DVT (painful blue leg) Necessity for parenteral narcotics Inability to have injections at home

Special Circumstances

Superficial Thrombophlebitis

Uncommonly evolves into a thromboemboic event

BUT, many patients have synchronous DVT (~8%)

Consider treatment with ASA or LMWH Then symptomatic treatment with:

NSAIDS Heat Graded compression stocking (30-40 mmHg) Ambulation

Case 2 44♂, painful swollen right calf Hx/PE:

3/7 days ago – dull ache No trauma/previous DVT Calf swollen 4cm, generally tender No other risk factors

U/S: Isolated calf DVT

How do you want to manage this?

Isolated Calf or Saphenous DVTCanadian Medical Associan Journal. 2003; 168(2)

Rarely causes leg symptoms (80% of symptomatic DVT involve proximal veins)

Rarely cause clinical significant PE

~25% of untreated calf DVTs will extend to involve the proximal veins

Vast majority of those that will progress do so within a week of presentation

Clinically this means that you can re-U/S them and hold the LMWH

(+/- ASA)

Phlegmasia Cerulea Dolens (Painful Blue Leg)

Massive iliofemoral occlusion results in swelling of the entire leg with extensive vascular congestion and associated venous ischemia

Leg is extremely painful and cyanotic Vascular surgery consult If timely consult not available, early

thrombolytic therapy maybe limb-salvaging

Upper Limb Venous ThrombosesBernardi, E., et al. 2001. Semin Vasc Med. 1;105-10.

Catheter related vs non ALL require treatment

High embolization rate If present, central venous catheters should

be removed

What’s new and exciting?

FondaparinuxMatisse Investigators. Ann Intern Med. 2004;140:867-73.

Synthetic polysaccharide Anti Factor Xa DBRCT Fondaparinux vs Enoxaparin in symptomatic DVT

2205 pts with symptomatic DVT from 154 centres worldwide Fondaparinux 7.5mg*sc od vs Enoxaparin 1mg/kg sc bid Outcomes:

Symptomatic recurrent VTE Bleeding Death

Fondaparinux Matisse Investigators. Ann Intern Med. 2004;140:867-73.

At least as safe and effective as LMH To date: no reported heparin-induced thrombocytopenia However, not available in Canada at this time

Other topics for you to think about

Superficial Thrombophlebitis Thrombolysis IVC filters

Pulmonary Embolus (PE)

BackgroundRosen’s Emergency Medicine: 6th Edition

PE results from a clot that formed hours, days, or weeks earlier in the deep veins which has traveled to the lungs

Presentation is highly variable EP’s probably correctly identify about half of pts with PE ~10% of ED pts die within 30 days even with prompt

diagnosis If no cardiopulmonary disease, 30% obstruction can be

tolerated with minor symptoms only

Case 3 61♀ presents to ED complaining of mild

pleuritic chest pain

Total knee arthroplasty 5/12 ago. Healthy otherwise

Tell me about: History Physical Investigations

Risk AssessmentEmergency Medicine Reports. 2004;25(11)

History and Physical do not confirm the diagnosis, they merely raise the suspicion of the diagnosis, triggering further investigation

Hx: Have to consider PE: dyspnea, tachypnea Pleuritic CP,

syncope, hypotension & hemoptysis Non-specific

PE: Tachypnea and tachycardia are most common

Risk AssessmentEmergency Medicine Reports. 2004;25(11)

CXR: Often AbN (Pleural effusion, atelectasis, elevated

hemidiaphragm) N CXR with dyspnea & hypoxemia = PE Know Hampton’s and Westermark for exams

EKG: Non-specific ST, Twave changes, Tachy

Signs of R heart strain (Anterior/Inferior T-wave inversions) Know SIQIIITIII for exams

ABG: Hypoxemia common, but not always present AAD02 >20 suggests PE (PIOPED) 25-35% of pts with PE have normal blood gasses, pulse ox, and

A-A gradient

Bottom Line

By themselves, H&P can help to stratify patients

But like w/ DVT, we now have standardized criteria

Pretest Probability Emergency Medicine Reports. 2004;25(11)

All decision trees start here Several exist Wells and Geneva validated Wells NPV: 99.5% Others more cumbersome to

use

Geneva (Wicki): add ABG, CXR

PISA-PED: Add ECG

Case 3 Continued HR: 104 Nil else

She gets 1.5 points

Now what? Do you even start to work her up for PE?

Pretest ProbabilityRosen’s Emergency Medicine. 6th Edition

One approach is to compare pretest prob with the “test threshold” Theoretical cutoff is pretest prob above which some workup

should be initiated and below which the pt would be harmed by further testing

Test Threshold for PE is ~1.8-2% Canadian (Wells) score <2 had probability of 1.3%

but not repeated How then?

Unstructured variable PE Rule Out Criteria Developed and validated in two

populations

PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Based on the premise that overuse of D-dimer to screen for PE can have negative consequences

Derivation phase: 3148 patients evaluated for PE in 10 US EDs Data collected on 21 variables Logistic regression and interobserver agreement used to

narrow to rule of 8.

PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Age <50 Pulse rate <100 beats/min Oxygen saturation >94% No hemoptysis No unilateral leg swelling No recent major surgery or trauma No prior pulmonary embolism or deep

venous thrombosis No hormone use

PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Validation Phase: 2 Groups

Low risk (board certified EP believed D-dimer warranted but good enough to r/o PE)

n = 1427, 114 (8%) had VTE diagnosed within 90d

Very low risk (chief complain dyspnea – PE not suspected)

n = 382, 9 (2.4%) had VTE diagnosed within 90d

PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55

Endpoint: VTE before 90 days. Good follow-up Both Wells score and PERC rule functioned relatively

well Wells better with very low risk population and included

more patients in both groups Both had very wide confidence intervals

PERC Rule – Bottom Line

Compliments clinical judgement DOESN’T REPLACE IT!

Pause before ordering a D-dimer in a patient

who does not have any of the eight criteria

Then order it if you still think it’s indicated

Case 3 Continued

Age > 50 HR >100 Does not meet PERC criteria. Wells 1.5

Send the D-dimer Result: 0.59 mg/L (↑) Does this mean anything? What if it was

1.9 mg/L?

D-dimer in PE

Does D-dimer level correspond to clot burden in PE?

What about mortality?

D-dimer in PEGrau, E. et al. Crit Care Med. 2007; 35:1937-41

Observational study of 588 pts with symptomatic PE Quantitative D-dimer performed on admission (Automated

Latex agglutination test) and clinical follow up for 90 days

D-dimer in PEGrau, E. et al. Crit Care Med. 2007; 35:1937-41

Compared to pts with D-dimer 500-2499 ng/mL, OR of 90d mortality: 1.91 (0.91 – 4.09) in pts with D-dimer 2500-4999 2.94 (1.42 – 6.45) in pts with D-dimer ≥ 5000

Pts with D-Dimer ≥ 5000 ng/mL: Higher risk of death from fatal pulmonary embolism OR 4.4

(0.5-33) than from other causes OR 2.1 (0.7-6.0) 95% CIs for odds ratios cross 1 More of a point of interest

= 0.5-2.49 mg/L

= ≥ 5 mg/L

= 2.5-4.999 mg/L

Confirmatory Testing Evaluation divided between screening and

confirmatory testing “Screening” is H&P, D-dimer Confirmatory:

Gold Standard ?still Angiography Landmark Articles used:

V/Q [Pioped I] CTPA [Pioped II] MRA [Pioped III]

PIOPED I – V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753

Multicentre study Sens/Spec of V/Q in setting of pre-test prob Reference standard was Angio/autopsy

PIOPED I – V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753

PIOPED I – V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753

Most important finding was that PE often present in non-diagnostic scans w/ high clinical probability

Except in low probability pts, low probability scans require additional testing CT or repeated Dupplex U/S (Rosen’s)

PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327

Prospective multicentre study, N = 824 Looking at the accuracy of CTA/CTV in setting of clinical

prediction tool (Wells) Composite reference standard (incl V/Q, Angio neg U/S)

CTA Report 51/824 inconclusive (6%) CTA Sens 83%, Spec 96% CTA-CTV inconclusive 87/824 CTA-CTV 90% and 95% Mostly 4-slice CT (didn’t have enough 8 & 16 slice to

comment)

PIOPED II – CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327

PIOPED II – Bottom LineLalani, N. Don’t Feed Me BS and Call it Candy. 2006

Didn’t really give us the answers that we wanted

Didn’t enroll 2/3 of eligible pts CT Scanners have evolved since Compared with V/Q, reports are far more

‘binary’ CT is probably better than this

Dutch study 510 pts all got spiral CT +/- U/S

Gold standard: 90d follow-up False Neg Rate 0.4%, Sens 99.6% 8/510 scans indeterminate angio

Multi-detector Row CTStork, A. Knows Too Much for Own Good. 2005

4,8,16, 64 row scanners Resolution <1mm

Visualization to 6th order vessels Entire chest scanned in <10seconds

Reduce number of non-diagnostic scans Less intravenous contrast Can be formatted to 2D and 3D images

Result Increased sensitivity for subsegmental PE

8-bit vs 64-bit resolution

CT vs AngiographyWlner-Muram, HT. et al. Radiology. 2004; 233(3):806-15

Prospective study of 93 pts (emerg and ward) in whom PE was suspected

4-slice CT and pulmonary angiography within 48h

SN: 100% SP: 89%

Meta-analysis of 23 studies Negative CT PE who didn’t receive AC 4657 patients

Results (3 month follow up) VTE: 1.4% (1.1-1.8%) Fatal PE: 0.51% (0.33-0.76%)

Conclusions CTPA has similar rates of recurrence as angiography Appears safe to withhold anticoagulation based on negative

CTPA

Outcomes: Multi-detector Row CTMoores, L., et al. Ann Intern Med. 2004; 141:866-874

15 Studies Reviewed, N=3500 Studies excluded:

D-Dimer used as initial triage tool Insufficient F/U (needed at least 3 months) Poor quality study (objective criteria)

NPV: 99.1% (98.7 - 99.5) NLR: 0.07 (0.05 – 0.11)

Outcomes: Multi-detector Row CTQuiroz, R., et al. JAMA. 2005; 293:2012-7

CTPE

Quick Widely available Relatively non-invasive Performs similarly to angiography Provides a “binary” outcome (interpreter

dependent) Can offer alternative diagnosis when PE is absent

CTPE - Weaknesses Poor ability to detect small, peripheral PE’s

?Clinically relavence

Protocol variability (slices, legs, venogram included)

Interpretation variability (day/night, staff/resident)

Radiation Contrast (anaphylactoid reactions, nephropathy) Pts may have contraindications

CT Scanning: Bottom Line

CTPA should be considered as good as the gold standard

When used with DD and U/S, NPV of >95%

Magnetic Resonance AngiographyFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

Advantages: Eliminates radiation Probably safer in pregnancy Decreased nephrotoxicity

Disadvantages: Cost Availability Failure to demonstrate adequate SN in

preliminary studies

PIOPED III – MR-A Purpose

Determine accuracy of Gd-MRA of pulmonary arteries with MRV of the thigh veins in pts with clinically suspected PE

Rationale: In PIOPED II, 25% had contraindications to CTPA/Angio such patients could benefit from safer MR

Expect 1250 pts (lots of exclusions incl Pregnant)

Calgary is one of the Centres

Real-Life AproachFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

CHR Approach

Again, the next 4 slides describe the current Calgary Health Region approach

Even fewer people use this than the DVT model: Released before PIOPED II (CTPE not

included) V/Q results don’t tend to be this

straightforward

Wells Criteria for Probability of PE

Clinical Hx/Sign Criteria Points

1. S/S of DVT leg swelling – objectively measured

AND pain with palpation in the deep vein region

3.0

2. Pulse>100/min 1.5

3. Immobilization bedrest (except access to BR) > 3 days

OR surgery in previous 4 weeks

1.5

4. Previous DVT or PE Must have been objectively diagnosed 1.5

5. Hemoptysis 1.0

6. Malignancy receiving active treatment for cancer

OR have received treatment for cancer in past 6 mo.

OR are receiving palliative care for cancer

1.0

7. PE as likely or more likely than an alternative Dx.

No specific criteria – use Hx, Physical, CXR, EKG, and labs to decide

3.0

Total Points Probability LR<2 LOW 0.122-6 MODERATE 1.90>6 HIGH 6.00

LOW PROBABILITY PE:

D-Dimer

Neg Positive

STOP VQ Scan

Normal

STOP

Non-high High

CUS legs

Normal DVT

Pulm Angio

Normal Positive

CUSIn 1 week

TREAT STOP TREAT

MODERATE PROBABILITY PE:

D-Dimer

Neg Positive

STOP VQ Scan

Normal Non-high High

CUS legs

Normal DVT

CUSIn 1 week

TREAT

TREAT

Pulm Angio OR

HIGH PROBABILITY PE:

VQ Scan

Normal Non-high High

CUS legs

Normal DVT

CUSIn 1 week

TREAT

TREAT

Pulm Angio OR

Pulm Angio OR OR Pulm Angio

What does the expert say?Wells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50

Divide pts into PE likely (Wells >4) or unlikely (≤4)

Case 3 Continued Recall… Low probability (Wells 1.5) D-Dimer: Positive Therefore...

CTPE Positive

Treatment Emergency Medicine Reports. 2004;25(12)

1. First decide primary therapy Significant clot burden immediate removal

Chemical - thrombolysis Mechanical – embolectomy

Less Significant Anticoagulation UFH, LMWH, Coumadin

2. Next decide prevention against future emboli

Anticoagulation IVC filters

Fibrinolysis Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)

Massive PE: PE with systemic arterial hypotension, cardiogenic

shock, severe dyspnea or respiratory failure Multiple case reports/series of improved outcomes and

ROSC Kucher et al. 2006: no change in mortality or recurrence

of PE

Submassive PE: PE occurring in hemodynamically stable patients

with evidence of right ventricular heart strain, as seen on ECG or echocardiography NEJM 2002; 347(15) –100mg alteplase in addition to

heparin improves clinical course (ARR = 13.6%, P=0.006)

Fibrinolysis in sub-massive PERamakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)

Results of randomized trials comparing the addition of thrombolytic therapy to standard heparin therapy for treatment of submassive pulmonary embolism fail to show any significant differences in clinically important outcomes. [Ann Emerg Med. 2007;50:78-84.]

Fibrinolytics – Bottom Line

Consider in PE with hypotension or systemic hypoperfusion or in the rapidly deteriorating patient

Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016

1. Is it technically possible? Newer treatments allow out-pt treatment of VTE

LMWH SC UFH

2. Is it safe? Pts at high risk of “badness” shouldn’t go home

Massive & Submassive PE – no brainers Risk stratify the rest:

Geneva Risk Score Pulmonary Embolism Severity Index (PESI)

V. Low Risk = 1.1% 30d Mortality

Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016

3. Is outpatient treatment appropriate in THIS patient?

Medical and Social Issues:

Bleeding risk, underlying malignancy, renal status, obesity, heart failure, thrombophilia, and concomitant medications that interact with anticoagulants (aspirin, clopidogrel, NSAID etc)

Medication compliance, availability of home-care, living situation, logistics of bloodwork

Out-Pt Treatment of PE Bottom Line:There is no consensus on who can safely be

treated at home

If the patient is hemodynamically stable, with no signs of R heart strain and otherwise

completely healthy, consideration of out-pt treatment is reasonable.

Would make this decision in discussion with pulmonary or the patient’s FP.

Wait, is she just a little hefty or…?

Common – VTE most frequent cause of death in pregnancy 0.5-3.0 / 1000 pregnancies

Most trials exclude pregnant pts D-Dimer is less specific!

More false positives more work-up US is great…if there’s a DVT

+ in 13-15% with suspected PE What about CTPE? V/Q? MRI/A not studied yet

PE in PregnancyWiner-Muram HT, et al. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology 2002;224(2):487–92.

Historically, V/Q recommended less radiation

Newer scanners supposed to be better? V/Q still gives indeterminate results Study used US to determine fetal

geometry Monte Carlo method for measuring

radiation dose of helical CT 2.5mm cuts to 4cm below xiphoidAverage fetal radiation dose with helical CT is less

than that with V/Q lung scanning during all trimesters. Pregnancy

should not preclude use of helical CT for the diagnosis of PE.

PE in PregnancyCook JV, Kyriou J. Radiation from CT and perfusion scanning in pregnancy. BMJ. 2005;331:350.

Compared maternal and fetal-absorbed doses (16-slice)

Maternal whole body effective dose: CTPE: 2 mSv V/Q: 0.6 mSv

Fetal absorbed doses: CTPE: 0.01mGy (1/1 000 000 risk of Ca by age 15) V/Q: 0.12 mGy (1/280 000)

Breast absorbed doses: CTPE: 10 mGy V/Q: 0.28 mGy

CTPE: less risk to fetus, more to mom’s breasts

PE in Pregnancy - Treatment

Same as other populations except Warfarin Known Teratogen don’t use.

Bottom Lines History and Physical are insensitive and

non-specific Use them to determine pretest probability

D-dimer is a sensitive screening test But not benign – use your head Remember PERC “rule” – only a guideline

All upper limb DVT require treatment CTPE is very powerful when combined with

DD, U/S If neg – safe to withhold treatment