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Venous Thromboembolic Disease. Chris Hall, MD, FRCPC Emergency Medicine Resident Rounds January 12, 2012. One Night in the ED…. 36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx : Nil Meds: None ECG, CXR normal. WHY I HATE PE…. - PowerPoint PPT Presentation
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Venous Thromboembo
lic DiseaseChris Hall, MD, FRCPC
Emergency Medicine Resident RoundsJanuary 12, 2012
One Night in the ED…
36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx: Nil Meds: None ECG, CXR normal
WHY I HATE PE…
Potentially fatal (“can’t miss”)
Challenging to diagnose
Evidence base is HUGE… and growing
Rapid advances in technology: evidence is obsolete (?!)
Objectives
To simplify YOUR life when it comes to PE in the ED
To provide an update on the latest state of the evidence regarding PE: Diagnosis Management Risk Stratification
Epidemiology
PE Incidence 115 cases per 100,000 population / yr
Mortality Rate 12 per 100,000 / yr
Case Fatality 8% overall (30% if untreated!)
Pathophysiology
Virchow’s Triad Stasis Injury Hypercoagulability
> 90% Deep venous source Iliofemoral > Pelvic > Renal > IVC Calf veins (< 10%)
Pathophysiology
Multiple mechanisms of hypoxia V/Q mismatch Inflammatory cascade surfactant dysfxn Functional intrapulmonary shunting
75% obstruction of PA bed = reduced CO
Risk Factors
Malignancy Immobilization / Paresis Surgery / Trauma Prior hx of VTE Thrombophilia Family history Pregnancy Estrogen use
PE: Our Worst Nightmare…?
Presentation often non-specific
Many clinical mimics
Up to 40% of fatal PE < 35 yo missed on first MD contact
…or an iatrogenic epidemic?
1998 – 2006: PE Indicence 86% Case Fatality 36% CTPA use > 10-fold Pop’n Mortality: NO CHANGE More testing / treatment to
get the same result?
A Balance of Risks
PE mortality: 8% (?? 25-30% if
untreated)
LAR for cancer from one CTPA 25yF: 1 / 400 55yF: 1 / 950 25yM: 1/ 2000
Contrast nephropathy
Overanticoagulation
More investigation
Fewer missed PE
Less Investigation
More missed PE??
??
What Risk is ‘Acceptable’?
At what pre-test probability would you discharge your patient without further testing? 10% 5% 2% 1% 0.5% 0.1%
What Risk is ‘Acceptable’?
Lessler et al, Ann Emerg Med 2010 Theoretical decision analysis Risk of missed PE vs. risk of investigation /
overtreatment At 1.4% probability, risks are equal
If probability of PE < 1.4%, do not test
Can clinical exam achieve PTP < 1.4%?
PE: Clinical Presentation
What symptoms / signs make you think of PE?
What is the most common symptom / sign?
Clinical PresentationSymptom % of PEDyspnea At rest Exertional only
61%16%
Chest Pain Pleuritic Non-pleuritic
47%17%
Cough No blood Hemoptysis
32%11%
Orthopnea 36%Syncope 12%
Clinical PresentationSign % of PE
Tachypnea 57%Signs of DVT 47%Tachycardia 29%Abn. Lung Sounds
26%
Fever 2%
One Night in the ED…
36 yo Female Sudden onset right-sided pleuritic CP Feels SOB Physical examination ‘normal’ PMHx: Nil Meds: None ECG, CXR normal
Would You…
Send a d-dimer?
Proceed directly to imaging?
Do nothing?
Is this patient’s pre-test probability of PE below the “no-test” threshold?
Wells Rule
Geneva Rule
55,268 patients
10 CDRs + MD gestalt reviewed
CDR SN SP NLR PLR
Wells 84 % 58 % 0.3 2.0
Geneva 84 % 50 % 0.3 1.7
Revised Geneva
91 % 37 % 0.2 1.4
MD Gestalt 85% 51 % 0.3 1.7
PERC
Pulmonary Embolism Rule-out Criteria Derived 2004 Validated 2008 (multi-center) Provides CLINICAL basis to rule out PE GOAL: < 1.5% probability
PERC
PERC Validation 8138 patients Results:
SN 97.4% (if MD gestalt ‘low-risk’) Post-test prob: 1.0%
PE prevalence 7% (3% in low-risk pts) Only useful in ‘low-risk’ population (MD
gestalt)
(BUT - who qualifies?? < 5% PTP?? )
Caveat Emptor…
Hugli et al. J Thromb Haemost., Feb 2011 1675 consecutive patients 21.3% prevalence of PE
Low-risk revised Geneva: 6.4% PE Low-risk Geveva + PERC (-): 5.8% PE
PERC NLR = 0.63 in LOW RISK pop’n
PERC Bottom Line
Achieves ‘no-test’ threshold in ‘low-risk’ patients
Endorsed in ACEP Clinical Policy (2011)
Select patients carefully
Back to our case
How many will now send a d-dimer?
The test you love to hate…
D-dimer = FDPSN 75 – 97%SP 43 – 99%Depends on assay typeDepends on clinical context (CDRs)
Higher PTP = Lower SN
Low
Not Low
(-)
(+)
‘Wells Rule’
Quantitative D-dimer + CDR
CDR Failure Rate Efficiency
Simplified Wells (≤4)
0.5 % 39 %
Geneva 0.0 % 21 %
MD Gestalt ** 0.7 % 52 %
D-dimer: Bottom Line
In low-intermed. probability patients, d-dimer rules out PE
ACEP Clinical Policy 2011
Efficiency of PERC + CDR / d-dimer strategy unknown
Not HighHigh
Yes No
Positive Negative
Back to our case…
D-dimer result = 0.89 Patient remains stable Do you now:
Order a V/Q scan? Order a CTPA? Order U/S dopplers of the legs?
PE: Imaging
What is the ideal strategy for imaging in suspected pulmonary embolism?
V/Q Scan
Advantages Lower radiation dose (7 – 10 x less than CTPA) No iodinated contrast
Disadvantages Harder to obtain ‘after hours’ Higher rate of non-diagnostic scans Cannot diagnose other causes for symptoms
CT diagnosed more PE 19.2% vs 14.2%
LARGE non-diagnostic V/Q scan rate (> 50%) V/Q noninferior to CT
VTE @ 3 mos 1.0% vs 0.4%
V/Q Scan: Don’t Bury it Yet!
Good option if:
Normal CXR
Younger patients
Lower PTP
Contraindications to CT
CT Pulmonary Angiogram
Advantages Speed Available after hours (in Calgary) Confirms alternative diagnoses
Disadvantages Contrast load Radiation dose
Our ‘de facto’ gold standard
3306 consecutive patients Utilized dichotomous Wells (≤ 4 = “low”)
D-dimer if Wells low; MDCT if d-dimer (+) or Wells high
No Rx if d-dimer (-) or MDCT (-)
VTE rate @ 3 months: 0.5% for Wells / d-dimer (-) 1.3% for CT (-)
PIOPED II CTPA SN: 85% VTE @ 6 mos: 14% for Int. / High PTP if CTPA
(-)
CTPA Bottom Line:
For Wells ≤ 4, CTPA (-) rules out PE If PTP ‘intermediate’, consider additional
testing** if still ‘concerned’ about PE If PTP ‘high’, obtain additional testing**
ACEP Clinical Policy, 2011
**(D-dimer acceptable)
What if I add CTV?
~ 2 – 4% pick-up of isolated DVT
Universal CTV use still controversial Intermediate – High PTP would benefit if CTPA
(-)
More studies using newer technology are needed
U/S: 1st-Line Imaging?
Righini et al., Lancet 2008 1819 patients with suspected PE U/S eliminated need for CTPA in 10%
“NNI” = 10
In both trial arms 3-month VTE risk = 0.3% CT-only arm 24% less expensive
Venous Imaging: Bottom Line
Routine venous imaging not usually recommended
Consider U/S first if: Leg symptoms present CT contraindicated or unavailable
Our Case…
CT refused RE: pregnancy test (+)
Diagnostic Controversy: PE in Pregnancy
Pregnancy = PE Risk factor Overall risk still low: 10.6 / 100,000 Risk greatest in post-partum period 3-6% of suspected cases are PE (+) PE symptoms overlap with changes of
pregnancy Strong desire to avoid ionizing radiation in
workup
PE in Pregnancy: D-dimer
True prognostic value unkown EVIDENCE IS WEAK on either side ESC Guidelines: USE D-DIMER TO R/O PE! ATS Guidelines: DO NOT USE D-DIMER TO R/O PE! “Kline” protocol:
PERC + TM-specific cut-offs
PERC alone may be good enough (~5% PTP)
PE Imaging in Pregnancy
U/S 1st-line if DVT symptoms; if no leg symptoms – skip it
V/Q If CXR normal, > 90% of scans are “definitive” Fetal radiation similar / maternal lower than CT *** Preferred 1st-line test
CT 30% of scans ‘non-diagnostic’ 1st-line if CXR abnormal
1/10,000 risk 10 mSv
of CA by age 25
NCRPM Cut-off 50 mSv
Background 5 mSv
radiation over 9 mos
V/Q scan0.32-0.74
mSvCTPA0.03-0.66
mSv
CXR0.002 mSv
You Call THAT Simplified??!!
MY approach
‘PERC’ them
D-dimer w/ ‘standard’ cut-offs
CXR
V/Q
(U/S first if leg symptoms)
Case
CTPA result: Several right-side PE Moderate clot burden RV normal
Treatment? Disposition?
PE: Treatment
LMWH is preferred Warfarin is OAC of choice Dabigatran: ? Non-inferior to warfarin IVC Filters:
Absolute CI to anticoag Failure of warfarin
Treatment Duration
Condition Duration of TherapyReversible cause
3 months
Idiopathic (1st)
3 months minimum; indefinite if low bleed risk
Idiopathic (2nd +)
Indefinite
Cancer LWMH x 3-6 mos, then warfarin until CA “cured”
Source: ESC PE Guidelines, 2008
Management:Sub / Massive PE
Massive PE: SBP < 90 mmHg (w/o other cause) Pulselessness HR < 40 with shock
Submassive PE: Not hypotensive RV dysfunction (+) Myocardial necrosis (+)
Supportive Care
IV Fluids Use caution: 250-500cc then consider echo
Pressors Levophed or dopamine OK; phenylephrine less
OK
Intubation Keep PEEP low (< 6) Use low TV (6cc/kg)
Thrombolysis
Indicated in massive PE AHA & ACEP endorsed NNT = 10
Subset of submassive PE may benefit Progressive deterioration (AHA) Insufficient evidence (ACEP)
Thrombolysis
Secure Dx before Rx CT vs echo
Alteplase 100mg IV preferred Bolus vs infusion / 2hr UFH infusion after
Avoid in undifferentiated VSA
Adjuncts
Catheter fragmentation Surgical Embolectomy Pulmonary vasodilators
NOx Sildenafil Inhaled prostacyclin
IVC Filters
Risk Stratification
Many (most?) jurisdictions practice universal admission
Calgary (Canadian?) practice heavily outpatient-based
Who is safe to d/c home?
Risk Stratification
Potential Tools Biomarkers
Imaging
Clinical risk scores
Troponin
Conventional Tn useful if positive: OR = 5.3 (short term death) SN = 70.5, NLR = 0.42
Becattini et al, Circulation 2008
hs TnT better for rule-out use: OR = 5.0 SN = 87.0, NLR = 0.31
Lankeit et al, Circulation 2011
Imaging
RV Dysfunction CT: debated Echo: gold standard ECG Useful if positive, less so if negative
CT ‘clot burden’ not predictive
Pulmonary Embolism Severity Index
Prospectively validated Purely clinical variables For STABLE patients SN ~ 95%; NLR ~ 0.1 for 30-day mortality
< 1% in low-risk 8-9% in non-low-risk
30-40% of patients are low-risk
Simplified PESI
PESI in Practice
Lancet, 2011 RCT of inpatient vs outpatient for PESI class
I / II 30-day mortality very low (< 1% overall) No difference between groups
Risk Stratification Pearls
Outpatient Rx: Low-risk PESI / sPESI
No RV dysfunction on echo / CT / ECG
Negative TnT / hsTnT
Case Conclusion…
Patient does not have a GP
What follow-up is needed?
Anticoagulation Clinic
Single visit; subsequent follow up on phone
Rely on GP for additional work-up
Director (MD) available for help if needed
Malignancy Screening
10% risk of malignancy in ‘idiopathic’ VTE Highly age-dependent Aggressive screening identifies more CA
sooner Guidelines suggest symptom-based
screening DO A THOUROUGH Hx & P/E Consider aggressive screen if > 60yo
Summary
PERC is useful if low-risk population D-dimer + CDR highly sensitive and moderately
efficient Don’t bury the V/Q yet! Routine venous imaging generally low-yield V/Q is preferred 1st-line image in pregnancy PESI can identify low-risk patients for outpatient Rx Consider a malignancy screen in older idiopathic VTE
Questions?
CASE 2
56 yo male 3 weeks post-op for TKA Unilateral calf swelling, erythema, and
tenderness x 2 days No trauma No chest pain / SOB No fever
Deep Vein Thrombosis
DVT: Objectives
Diagnosis of DVT Diagnostic algorithms
Novel ED-based imaging strategies
Treatment of DVT Complications / special scenarios
Epidemiology
Risk = 1.92 / 1000 person-years Higher risk in men 50% will embolize eventually (PE) 30% have silent embolism at diagnosis
Pathophysiology
Virchow’s Triad
50% will embolize eventually
30% have silent emboli @ diagnosis
Classification
Risk Factors
See PE… PLUS:
IVC anomalies
May-Thurner Syndrome
Clinical Presentation
Pain / tenderness Erythema / warmth Swelling / edema Venous distension
+/- ‘palpable cord’
Homan’s Sign “Phlegmasia Cerulea Dolens” / “Phlegmasia Alba
Dolens”
Differential Diagnosis
Baker’s Cyst Cellulitis Venous Insufficiency Swelling due to paralysis Lymphangitis / lymphatic obstruction Non-specific swelling
Our Case
Does this patient have a DVT?
Can clinical features r/o DVT?
Wells’ DVT Criteria
Predicting DVT Clinically
Wells Score
PTP of DVT
Low 5%
Intermediate 17%
High 53%
D-dimer
Wide range of sensitivities / specificities ELISA generally higher SN / lower SP than
SimpliRED Primary utility is when combined with PTP
D-dimer
Wells Score
SN SP LR (+) LR (-)
Low 95% 58% 2.4 0.10
Moderate 98% 41% 1.7 0.06
HIgh 97% 36% 1.5 0.07
D-dimers: Bottom Line
In Low-Risk group, NLR is sufficient to R/O DVT
In other groups, d-dimer insufficent to change decision to image
DVT: Imaging
Venography Impedance Plethysmography CT Venogram MRI Venogram
U/S for DVT
Defacto ‘gold standard’ No ionizing radiation No IV contrast Generally widely available Variable techniques
Whole-leg Doppler 2-point proximal vein compression
Whole-Leg U/S
Detects calf vein DVTs Equivalent to strategy of serial proximal
compression U/S plus d-dimer May eliminate need for serial U/S Not performed routinely at AHS sites
ED Ultrasound
Available “24 / 7” Easy to learn Variable SN: 70-100% depending on author Accuracy likely improved w/ clinical risk
stratification
DVT Treatment
LMWH UFH Fondaparinux Warfarin Dabigatran
LMWH
Preferred 1st-line agent Better outcomes than IV UFH OD / BID dosing Predictable anticoagulation effect No monitoring needed Lower risk of HIT SAFE in pregnancy
SubQ UFH
Equivalent to LMWH BID dosing (weight-adjusted, fixed-dose) Monitoring of APTT likely NOT needed Less concern in renal failure Risk of HIT Less expensive than LMWH
Fondaparinux
Non-inferior to LMWH OD dosing (weight-based, fixed-dose) No monitoring needed Can be used (with limits) in renal failure (CR
< 260)
Wafarin
OAC of choice Initial 5-7 days need overlap with an anti-
thrombin INR monitoring required UNSAFE in pregnancy
Dabigatran
Oral anticoagulant; Non-inferior to warfarin No monitoring required Not yet approved for use in VTE
Other Therapies
IVC Filter Failed anticoagulation Contraindications to A/C
Catheter procedures (incl. thrombolysis) Circulatory compromise (PCD) IFDVT w/ rapid progression despite A/C “Selected” patients w/ IFDVT
Stenting Advanced PTS / venous ulcers in setting of IFDVT
Condition Duration of TherapyReversible cause
3 months
Idiopathic (1st)
3 mos minimum (6 mos IFDVT); indefinite if low bleed risk
Idiopathic (2nd +)
Indefinite
Cancer LWMH x 3-6 mos, then warfarin until CA “cured”
Calf DVT 6 wks – 3 mos
Summary
Clinical exam insufficient when used alone D-dimer useful only in lowest-risk group Consider serial U/S if d-dimer (+) in non-
low-risk patients LMWH / Warfarin are first-line agents
Questions?
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