pulmonary embolism and deep venous thrombosis james huffman 11.13.2008 thanks to dr. gil curry, dr....
TRANSCRIPT
PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS
James Huffman
11.13.2008
Thanks 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/INR
Warfarin
PT/INR
Warfarin
PTT
Heparin
PTT
Heparin
Anatomy
Depth Deep Superficial*
Proximal Popliteal v. or
higher Distal
*Superficial femoral vein is a member of the deep group
*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 Polycythemia
Endothelial Injury: Stroke Vascular surgery PVD
Others: 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!
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 usesCHR 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)
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
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= 0.5-2.49 mg/L
= ≥ 5 mg/L= ≥ 5 mg/L
= 2.5-4.999 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.]
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
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 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.
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 xiphoid
Average 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.
Average 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
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