Transcript et al - Calgary Emergency Medicine

DVT
& PE
James Huffman &
Dr. Trevor Langhan
11.12.2009
• DVT
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Diagnostic Algorithm
Determining Pre-test Probability
Useful Diagnostics
Treatment
Disposition
Special Circumstances
• PE
– Similar topics, PLUS:
– Controversies
Virchow’s Triad
White, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003.
1. Injury to the vascular
endothelium
2. Alterations in blood flow
3. Hypercoagulability
Anything else associated with
imbalanced clot formation?
Age
Case 1
• 55♀: Referred to ED for pain, redness and
swelling of the right calf
– WIC today: Sent to ED with note:
Diagnostic Approach: Pre-test Probability
Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087
DVT: History & PE are Risk
Assessment
• Goals of H&P?
– Determine pre-test
probability
– Look for other causes
Case 1: History & Physical Exam
History & Physical are Risk Assessment
Anand, 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
Pretest Probability
Pretest Probability
• This algorithm re-presented in JAMA rational
clinical examination series
Anand 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 Dimer!
D-Dimer Testing
Kline, et al. Ann Emerg Med (2003); 42(2): 266-275.
 Degradation product of fibrin
 Non-specific
– PPV bad
– +ve: surgery, trauma,
hemorrhage, CA, pregnancy,
sepsis, >80 yrs old
Assay
Sensitivity Specificity
 Sensitivity variable
Whole blood
agglutination
(SimpliRED)
80-85%
70-90%
 Need Pre-test probability to r/o
DVT
Latex
agglutination
90-95%
40-90%
Rapid ELISA
95-100%
30-60%
CLS uses
Clinical Variable
Score
“Active” Cancer (treatment ongoing, within 6 months or palliative)
1
Paralysis, Paresis or recent casting of lower extremities
1
Recently bedridden 3 days or more, or Surgery A in past 3 months
1
Localized tenderness along distribution of deep venous system
1
Entire leg swollen
1
Calf swelling at least 3cm larger than asymptomatic leg
1
Pitting edema confined to the symptomatic leg
1
Collateral superficial veins (Non-varicose)
1
Previously documented DVT
1
Alternative Diagnosis at least as likely as DVT
-2
D-Dimer Testing
Wells, P., et al. 2003. NEJM: 349(13); pp1227-35
RCT (N=1096)
D-Dimer vs no D-Dimer
DVT unlikely (Wells < 2)
# of U/S per pt decreased in
D-dimer group (0.78 vs 1.34)
D-Dimer Testing
Wells, P., et al. 2003. NEJM: 349(13); pp1227-35
• “Modified” Wells Criteria
• Used SimpliRED and IL-Test assays (less sens than ours)
•
Conclusion:
– Wells <2 and negative D-Dimer can safely r/o DVT
Level 1 – Pretest Probability
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”)
So she gets either 4 or 2 points = DVT likely
What next Einstein?
Level 2 – D-dimer
• Her d-dimer was positive at 1.23
Level 3 – Ultrasound (or not)
Ultrasound
American Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66
Bottom line: U/S is the test of choice for
DVT
Anatomy
Emerg Med Clin N Am. 26 (2008)
• Depth:
– Deep
– Superficial*
• Proximity:
– Popliteal v. or
higher
– Distal
*Superficial femoral vein is a
member of the deep group
Ultrasound
Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83
Bedside U/S?
Jolly BT, et al. Acad Emerg Med 1997;4(2):129–32.
Frazee BW, et al. J Emerg Med 2001;20(2):107–12.
• 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
• 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.
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–
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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-Venography
Goodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 1071–6
DVT: Bottom Line Thus Far?
1. Hx/PE help decide pretest probability (Wells)
2. Add a sensitive test (D-Dimer)
3. Almost all cases, do a sensitive confirmatory test
(U/S)
Case 1 Continued
• Okay back to it…
• U/S shows popliteal vein DVT
• Management Doctor?
Level 4 - Treatment
Medical Management
Rosen’s Emergency Medicine 7th Edition
Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087
Treatment: Bottom Line
• IV UFH, LMWH,
Fondaparinux are all
acceptable
Case 1 Conclusion
• Pt started on Enoxaparin and Warfarin
• Arranged to see her oncologist and a
hematologist as out-patient 2 days later
• In General, discharge home is safe.
• Admission may be required if:
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–
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Renal failure, high bleeding risk
Extensive DVT (painful blue leg)
Necessity for parenteral narcotics
Inability to have injections at home
Special Circumstances
Superficial Thrombophlebitis
Rosen’s Emergency Medicine 7th Edition
• Uncommonly evolves into
a thromboemboic event
• BUT, ~8% of patients have
synchronous DVT
Isolated Calf or Saphenous V. Thrombosis
Canadian Medical Association Journal. 2003; 168(2)
• Rarely cause significant PE
• 25% of calf DVT extend to involve
proximal veins
• Vast majority will extend within 7d
• DVT complications in 10-38%
(untreated)
Clinically this means you can Rx ASA (325mg/d) and arrange
for re-U/S in 7d or just start on full DVT anticoagulation
Phlegmasia Cerulea Dolens
(Painful Blue Leg)
Pulmonary Embolism
Case 2
• 61♀ presents to ED complaining of mild pleuritic
chest pain
– Total knee arthroplasty 5/12 ago. Healthy otherwise
Risk Assessment
Emergency 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
Pretest Probability
Emergency Medicine Reports. 2004;25(11)
•
•
•
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All decision rules start w/ score
Wells and Geneva validated
Wells NPV: 99.5%
Others more cumbersome
• Geneva (Wicki): adds ABG, CXR
• PISA-PED: Adds ECG
Bottom Line:
Use history & physical exam risk stratify patients
Wells ≤ 4  PE Unlikely
Wells > 4  PE Likely
H&P are Risk Assessment
Wells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50
Wells ≤ 4  Unlikely
Wells > 4  Likely
Risk Assessment
Emergency 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
– Simultaneous TWI in V1 and III are highly specific
• 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
Case 3 Continued
• HR: 104
• Nil else
• She gets 1.5 points
• Now what?
• Do you even start to work her up for PE?
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 inter-observer 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
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•
•
•
•
•
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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:
1. 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
2. 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 <2 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 judgment
– 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 2 Continued
• Age > 50
• HR >100
• Does not meet PERC criteria. Wells 1.5
–  Send the D-dimer
– Result: 0.59 mg/L (↑)
PIOPED I – V/Q Scanning
PIOPED Investigators. JAMA. 1990;263:2753
PIOPED I – V/Q Scanning
PIOPED Investigators. JAMA. 1990;263:2753
PIOPED II – CTA / CTV
Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
CTA inconclusive: 6%
CTA Sens: 83%, Spec:
96%
CTA-CTV 90% and 95%
PIOPED II – CTA / CTV
Stien, P. NEJM. 2006. 354; 22, pp 2317-2327
8-bit vs 64-bit resolution
Outcomes: Multi-detector Row CT
Moores, L., et al. Ann Intern Med. 2004; 141:866-874
• 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
Bottom Line
Multi-detector row CTPA should be
considered the “gold standard”
Magnetic Resonance Angiography
Fields, 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
Case 3 Continued
•
•
•
•
Recall…
Low probability (Wells 1.5)
D-Dimer: Positive
Therefore...
– CTPE  Positive
Treatment
Emergency Medicine Reports. 2004;25(12)
Houman et al. J Thromb Thrombolysis. 2009. 28:270-7
1. First decide primary therapy
– Significant clot burden  immediate removal
• Chemical - thrombolysis
• Mechanical – embolectomy
– Less Significant Anticoagulation
• UFH, LMWH, (Fondaparinux)  Coumadin
2. Next decide prevention against future emboli
– Anticoagulation
– IVC filters
Spectrum of PE
Kearon et al. 2008 Chest.
• Massive (PE + shock)
– Thrombolysis + ICU
• Submassive (PE + NBP + RV Dysfxn)
– Admission, anticoagulation, +/- thrombolysis
• Symptomatic
– probable admission, anticoagulated, +/- echo
• Asymptomatic
– You probably don’t even know about it ….
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 PE
Ramakrishnan, 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 PE
Merli, 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 
GRS vs PESI
Jimenez. Chest 2007
• GRS
• PESI
–
–
–
–
–
–
–
–
Sn 34% (18-51)
Sp 85% (82-88)
PPV 11% (5-18)
NPV 96% (94-98)
Sn 81% (68-95)
Sp 37% (33-41)
PPV 7% (4-9)
NPV 97% (95-99)
Out-Patient Treatment of PE
Merli, 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 Pregnancy
Winer-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
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 Pregnancy
Cook 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 nonspecific
– 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
• CTPE is very powerful
– If neg – safe to withhold treatment
• Fibrinolysis if hypotensive, hypoperfused or
circling
Pretest Probability
Wells, P, et al. 1997. Lancet:350;1795.


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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]
Fixed dose subcutaneous low molecular weight heparins versus
adjusted dose unfractionated heparin for venous thromboembolism
Van 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
Fondaparinux
Matisse 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