PE / DVT

1
PE / DVT

• Andrea Wilson
• May 20/ 2004

2
Virchows triad

• Hypercoagulability
• Stasis
• Venous injury

3
Risk factors (EMR)

• Hypercoagulability
• Previous DVT/PE
• Malignancy
• Inflammatory conditions (SLE, IBD, PVD)
• Nephrotic syndrome
• Sepsis
• HIT
• Coagulation disorders
• Factor V Leiden mutation
• Resistance to activated Protein C 
• Protein S deficiency 
• Protein C deficiency 
• Antithrombin deficiency 
• Disorders of fibrinogen or plasminogen 
• Antiphospholipid antibodies (lupus anticoagulant
  and anti-cardiolipin)

• Increased estrogen
• (causes urinary loss of protein S and AT III)
• Pregnancy Post-partum lt 3 months
• Elective abortion or miscarriage
• OCP or other estrogens
• Intimal damage
• Intravenous drug abuse
• Trauma /Recent surgery
• Central lines
• Multifactorial
• Trauma
• Recent surgery
• Immobilization gt3 days
• Long trips gt 4hr in past 4 wks
• Age gt 60
• Cardiac disease MI, CHF
• Obesity

4
DVT
5
PATHOPHYSIOLOGY
INCITING EVENT INTIMAL DEFECT IN VEIN COAGULATION
CASCADE ACTIVATED AND PROMOTES PROXIMAL GROWTH OF
THROMBUS VENOUS HYPERTENSION DEVELOPS PAIN AND
SWELLING EMBOLIZATION (NOT UNIVERSAL)
6
PATHOPHYSIOLOGY
FIBRINOLYTIC SYSTEM OPPOSES COAGULATION
CASCADE CLOT ORGANIZES/DISSOLVES
(PARTIALLY) RECANALIZATION OVER SEVERAL
WEEKS FIBROBLASTS AND CAPILLARY DEVELOPMENT LEAD
TO INTIMAL THCKENING VENOUS HYPERTENSION AND
RESIDUAL CLOT DESTROY VALVES POSTPHLEBITIC
SYNDROME (EDEMA, SCLEROSIS, ULCERATION, ACUTE
EPISODES OF PAIN/SWELLING)
7
Pathophysiology

• most start in calf, extend proximally (90)
• 70 PE have DVT evidence at autopsy
• Symptomatic DVT in popliteal or prox veins in
  gt80 cases
• Most pts with symptomatic prox DVT but no chest
  sx have PE (40 high probability scans)- Kearon
• Anand 1999 says 50

Clive Kearon, CMAJ 2003 Tintinalli
8
History

• Many No Sx
• Leg pain in 50 -gt nonspecific
• Amount pain / tenderness do not correlate to
  severity
• What questions would you ask?

9
History

• 1. Have you or anyone in your family ever had a
  blood clot in their leg or lung?
• 2. Have you been on a long trip (e.g., car,
  plane, etc.)?
• 3. Have you recently been bedridden for more than
  three days?
• 4. Have you had surgery or trauma in the last 2-3
  months? 5. Have you been pregnant in the last
  three months (Therapeutic abortion, miscarriage,
  current pregnancy)?
• 6. Are you on birth control pills and do you
  smoke?
• 7. Do you have any medical problems (e.g.,
  malignancy, SLE, CHF)?
• 8.Have you had chest pain or shortness of breath?

Colucciello SA. Protocols for Deep Venous
Thrombosis (DVT) A State-of-the-Art Review Part
I Risk Factor Assessment, Physical Examination,
and Current Diagnostic Modalities. www.EMR
online
10
Physical

• No ONE reliable history / physical finding
• Sensitivity 60-96, Specificity 20-72
• Need to look _at_ combination of factors
• Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook
  D, Ginsberg JS. Does this patient have deep vein
  thrombosis? JAMA. 1998 Dec 2280(21)1828-9.

11
?
12
Physical

• Edema (unilateral) (gt 3cm)
• Homans (50 sens) USELESS
• Superficial thrombophlebitis (up to 40 can have)
• Fever (gt39.5, something else)
• Phlegmasia cerulea dolens
• Swollen purple leg re venous engorgement
• Cyanosis re massive venous obstruction
• Phlegmasia alba dolens
• Whitish inflammation associated with arterial
  spasm 2nd to massive venous obstruction
• Worry about arterial occlusion

13
Anand SS, Wells PS, Hunt D et al. Does This
Patient Have Deep Vein Thrombosis? JAMA 1998
279 1094-1099.
14
DIFFERENTIAL DIAGNOSIS

• cellulitis abscess
• Bakers cyst CHF
• MSK injury lymphedema
• postphlebitic syndrome malignancy
• superficial phlebitis factitious
• fracture AV fistula
• compartment syndrome acute arthritis
• nerve root irritation myositis

Colucciello SA. Protocols for Deep Venous
Thrombosis (DVT) A State-of-the-Art Review Part
I Risk Factor Assessment, Physical Examination,
and Current Diagnostic Modalities. www.EMR
online
15
Clinical PresentationDVT

• Calf-popliteal
• 80-90, many asymptomatic
• pain swelling
• spreads proximally
• Ileofemoral
• pain in buttock, groin
• thigh swelling
• 10-20 cases

16
Case

• 55-year-old woman
• pain, swelling, warmth, and redness R calf.
• She denies injury to the leg, or previous DVT.
• On IV chemotx for ovarian carcinoma dx 6 mos ago.
  Extensive pelvic LN involvement, RgtL, was present
  at diagnosis,
• ?due to extrinsic compression of the right iliac
  vein
• Now no LNs palpable recent pelvic U/S showed a
  reduction in the adenopathy.
• Pitting edema, erythema, increased warmth of R
  calf (gt 3.5 cm greater than L), tenderness of
  the popliteal vein.

Anand SS, Wells PS, Hunt D et al. Does This
Patient Have Deep Vein Thrombosis? JAMA 1998
279 1094-1099.
17
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) gt 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 gt3cm 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 lt 0 points
MOD PROB 1 or 2 points
HIGH PROB gt3 points
18
What if

• 60 yo man with calf swelling and active cancer
• ?
• D-dimer
• ?
• Duplex U/S negative
• ?

19
Algorithm for Suspected first DVTPerrier.
Lancet, 1999
20
LOW PROBABILITY DVT
D-Dimer
Neg
Positive
STOP
CUS legs
Normal
DVT
TREAT
STOP
21
MODERATE PROBABILITY DVT
D-Dimer
Neg
Positive
STOP
CUS legs
Normal
DVT
TREAT
CUS leg in 1 week
Normal
Positive
STOP
TREAT
22
HIGH PROBABILITY DVT
CUS legs
Normal
DVT
TREAT
Venography
Normal
Positive
STOP
TREAT
23
Incidence of DVT by Clinical Probability
24
D-Dimer

• Enzyme-linked immunosorbent assays, latex
  agglutination assays, and a whole blood
  agglutination test
• PPV poor NPV excellent
• NOT to r/o PE in high PTP

25
DIAGNOSIS BLOOD TESTS

• D-dimer
• degradation product of cross-linked fibrin
• measured by whole blood agglutination
  (SimpliRED), latex agglutination, and ELISA
• advantages rapid, 93 sensitive for proximal DVT
• disadvantages low specificity, false positives
  in patients with recent surgery/trauma,
  hemorrhage,recent MI/CVA, acute infection, DIC,
  pregnancy/recent delivery, active collagen
  vascular disease, liver disease, metastatic Ca,
  90 ve gt80 yrs old
• highest NPV in low risk patients

26
D-dimer AssaysVan der Graaf. Thromb Haemost,
2000.
27
Alveolar dead space?

• Alveolar dead space should increase after PE as a
  result of arterial vascular occlusion because
  some pulmonary segments are ventilated but not
  perfused.
• Kline et al (JAMA) evaluated the diagnostic
  accuracy of alveolar dead space determination
  d-dimer assay for dx of PE.
• combination of tests performs slightly better
  than either test alone (negative likelihood
  ratio).

Niemann JT. Diagnostic Accuracy of a Bedside
D-Dimer Assay and Alveolar Dead-Space Measurement
for Rapid Exclusion of Pulmonary Embolism A
Multicenter Study. Annals of Emergency Medicine.
2001 38 (6)
28
Ultrasound

• Duplex doppler ultrasound
• combines Doppler flow with 2D scanning
• Doppler component evaluates blood flow for
  proximal obstruction, color flow provides most
  accurate images, and 2D scan provides 2D image of
  vein and surrounding structures
• non-invasive, portable
• loss of compression DVT
• We dont look below popliteal

29
Diagnostic Imaging for DVT

• Duplex / compression U/S
• ve in 30-50 PE 5 non-dx V/Q scans
• 97 sensitive for acute thrombi above the knee,
  94specific (Tintinalli)
• Only 58 sensitive in asymptomatic DVT (Anand)
• also good for other causes of leg swelling
• limitations expensive, operator dependent, less
  sensitive for clots below knee (73), pregnancy,
  and nonoccluding thrombi, acute vs chronic

30
Serial Venous U/S

• may avoid angiography in ?PE
• In low-risk an initial N U/S or 2 done 1 wk
  apart carries a lt1 risk of symptomatic proximal
  DVT or PE at 3 mos.
• You can hold the anticoagulant if initial U/S
  negative (safe)
• 1-2 ve in 2 weeks (?PE)

31

• Anand et al 1999
• Making the point that if results are discordant
  then further testing needed.
• A lot of venography / different than ours.

32
Impedance Plethysmography

• measures change in lower extremity volume as a
  function of venous outflow in response to certain
  stimuli
• changes in calf circumference, cutaneous blood
  flow, or electrical resistance occur when there
  is obstruction of venous return
• Does not allow direct visualization of veins
• suggests that DVT is present when significant
  outflow obstruction present, (if no extrinsic
  venous compression or conditions associated with
  elevated central venous pressure).
• operator dependent

33
Impedance plethysmography

• IPG
• false positives occur in the setting of post
  phlebitic syndrome, abdominal tumors, pregnancy,
  and CHF
• sensitivity 73-96 , specificity 83-95, 97NPV
  (Tintinalli)
• sensitivity over a 10d-2 week follow-up period
  approaches that of ultrasound, thus used for
  outpt F/U (Calgary protocol is day 1, 4, 7, and
  10 after negative U/S at day 0)
• Not good for calf clots either

34
IPG vs. Doppler

• N985
• PPV U/S94 (CI 87-98)
• PPV IPG 83 (CI 75-90)
• P0.02
• Harriet Heijboer, Harry R. Buller, Anthonie
  Lensing, Alexander Turpie, Louisa P. Colly, and
  Jan Wouter ten Cate. A Comparison of Real-Time
  Compression Ultrasonography with Impedance
  Plethysmography for the Diagnosis of Deep-Vein
  Thrombosis in Symptomatic Outpatients NEJM Volume
  3291365-1369November 4, 1993Number 19.

35
U/S

• What if the U/S or IPG is inconclusive or there
  was a potential for false or false - results?
• With tx of proximal DVT, residual thrombosis is
  evident on U/S scans in 50 of pts after 1 yr
• Contrast venography or MRI

36
Venography

• ?Gold Standard?
• Invasive
• Contrast
• Need experienced readers
• Non-diagnostic up to 25
• May induce DVT in 3 (Anand)

37
DIAGNOSISIMAGING

• Venography
• gold standard, but
• radiologists interpretations differ 10 of the
  time
• 5-15 are inadequately done
• 2-5 of patients develop phlebitis (sup. or deep)
• risk of anaphylactoid reactions exists
• able to distinguish between acute and chronic
  events as well as collateral channels
• test of choice for the post-surgical patient as
  U/S not sensitive enough
• useful if U/S inconclusive

38

• Anand SS, Wells PS, Hunt D et al. Does This
  Patient Have Deep Vein Thrombosis? JAMA 1998
  279 1094-1099.

39
Diagnostic Imaging (Tintinalli)
Indication Sens (prox DVT) Pro Con
Duplex DVT 97 Noninvasive, finds alt dx Poor sens for calf
IPG No duplex gt80 Noninvasive Poor sens, false ,
Venography No duplex/ inconclusive 100 Accurate, sees calf DVT Invasive, painlful, contrast, PPS
Radionuclide study Inconclusive contrast C/I Variable (ok for calf) None Delayed result, , high false
MRI Inconclusive, pelvic DVT, pregnant gt95 Noninv, safe in preg, finds alt dx, acute vs chronic , time, magnet
40
Treatment

• Goal prevent PE

41
TREATMENT

• Unfractionated heparin
• works on intrinsic pathway
• activates antithrombin III to prevent conversion
  of fibrinogen to fibrin
• prevents extension of thrombus but does not
  remove existing thrombus
• narrow therapeutic window
• significant bleeding in 7-30 of patients
• thrombocytopenia in 3
• use weight based nomogram instead of fixed dosing
  (more patients therapeutically anticoagulated
  within 12 hours)
• largely replaced by LMWH for treatment of DVT

42
TREATMENT

• Low molecular weight heparin
• primarily inhibits factor Xa more so than IIa,
  therefore, doesnt affect PTT and no need for
  therapeutic monitoring
• greater bioavailability and more predictable
  therapeutic anticoagulant effect
• tinzaparin (Innohep) approved for use in Canada
  for DVT, enoxaparin (Lovenox) in the U.S.
• Can still test for hypercoagulable states
• reversible with protamine 1 mg/100 U LMWH
• continue until INR therapeutic for 2 consecutive
  days, then stop
• safety of home administration well-established

43
Treatment of VTEAnticoagulation

• LMWH superior to UFH? (Gould 1999)
• More predictable anticoag effect, easier, lower
  incidence of major bleeding and HIT, lower
  mortality, reduction in clot extension, fewer
  recurrent thromboembolic events
• out-pt Rx safe in PE (Kovacs, 2000)
• Cost-effective (Gould 1999)
• Only measure anti-Xa levels in renal failure pts.
• Avoid if CR gt 180 umol/L

44
Anticoagulation

• Enoxaparin 1mg/kg bid or 1.5mg/kg od (max 180 mg)
• Tinzaparin 175 anti-Xa u/kg od (max 18,000 U)
• Weight-based dosing (actual not ideal weight)
• start warfarin 5mg on day 1
• d/c LMWH when INR gt2.0 x 2 days
• Rx 3 mos if 1st and reversible cause
• 6 mos if non-reversible
• indefinite if recurrent, CA, genetic
• Anticoagulation Clinic

45
TREATMENT

• Warfarin
• acts on extrinsic pathway (factor VII) to inhibit
  vitamin K dependent factor synthesis (II, VII,
  IX, X)
• started same day as heparin
• theoretical risk of worsening thrombosis if
  started before heparin in patients with protein C
  or S deficiency (procoagulant effect) but studies
  have demonstrated safety of starting in ED
• INR between 2-3 provides adequate anticoagulation
  without serious increase in bleeding risk

46
TREATMENT

• IVC controversial no survival benefit
• If anticoag C/I, major bleed, HIT, persisting DVT
  or embolization after 1-2 wks therapeutic
  anticoag.
• Thrombolytics
• may have decreased risk of post-phlebitic
  syndrome over patients treated with heparin?
• increased risk of hemorrhagic complications over
  heparin has prevented its widespread use
• should be used for phlegmasia dolens if heparin
  fails (also consider thrombectomy)
• Consideration for extensive iliofemoral
  thrombosis and UEDVT SK or tPA heparin

47
Indications for Admission

• Unable to ambulate
• Poor social support
• Unreliable follow up
• Unable to educate re drug administration
• Need for lytic or invasive tx
• Query arterial ischemia, cellulitis or pelvic
  mass
• (Tintinalli)

48
SPECIAL CONSIDERATIONS

• Superficial phlebitis
• while isolated cases are benign and can be
  treated with NSAIDs and compression bandages,
• Incidence of DVT from extension of a superficial
  thrombus 3 but incidence of embolization very
  low
• recommended that all patients be followed
  serially with U/S or IPG to ensure no propagation
  to deep venous system
• Do F/U U/S in 1 week
• (Tintinalli)

49
SPECIAL CONSIDERATIONS

• Upper extremity DVT
• 2-4 of all DVT in axillary or subclavian V
• can cause PE (originally thought to be benign)
• etiology effort thrombosis in physically
  active people, thoracic outlet syndrome, cervical
  rib, central line, malignancy
• 25 Paget-von Schroetter syndrome
• Exertional DVT
• Caused by underlying MSK deformities

50
Upper Extremity DVT

• N58 Sx UEDVT
• IPG, Doppler, venography
• Test Sens Spec
• compression ultrasonography (96 and 93.5)
• color flow Doppler imaging (100 and 93)
• 27 (47) UEDVTPE Objectively found in 36
• 2 yr F/U 2 recurrent VTE
• RF
• CVC
• Thrombophilia
• Previous VTE

• Prandoni P, Polistena P, Bernardi E, et al
  Upper-extremity deep vein thrombosis. Risk
  factors, diagnosis, and complications. Arch
  Intern Med. 1998 Sep 28158(17)1950-2.

51
U/S Upper Extremity DVT

• The sensitivity of duplex ultrasonography ranged
  from 56 to 100, and the specificity ranged from
  94 to 100
• Unsure if Helpful
• Venography or MRI if high clinical suspicion but
  negative U/S
•  

• Mustafa BO, MD Rathbun SW, MD Whitsett TL, MD.
  Sensitivity and Specificity of Ultrasonography in
  the Diagnosis of Upper Extremity Deep Vein
  Thrombosis A Systematic Review Arch Int Med 2002
  162(4)401

52
Upper Extremity DVT

• Thrombus in 35-67 of long term CVC (Randolph)
• 10-30 incidence PE associated
• Meta-analysis by Randolph in Chest 1998 showed
  benefit of prophylactic heparin for CVC
• Therapy
• Anticoagulation alone
• Local thrombolytics appears to be Rx of choice
  with literature mainly case studies
• Look for underlying compressive abnormality
• /- SVC filter if C/I
• Consult your neighbourhood vasc surgeon

53
SPECIAL CONSIDERATIONS

• Calf DVT
• most DVTs start in calf, extend proximally (90)
• Isolated calf DVT extend proximally only 20 of
  time
• Usually within 1 week
• Nonextending calf DVT rarely cause PE
• it is not universally recommended that isolated
  calf thrombi require anticoagulation, but they at
  the very least require serial studies to ensure
  no progression
• Pelvic Vein Thrombosis
• Postpartum, PID, post pelvic surgery/tauma
• Non-spec abdo pain and vomiting
• MR or CT

54
PULMONARY EMBOLISM
55
Mortality

• Approximately 10 of patients who develop PE die
  within the first hour,
• 5-10 of PE have shock at presentation
• USA 60-80 patients with DVT, gt50 Sx free
• Autopsy studies 60 pts who die in hospital had
  PE, diagnosis missed in gt50
• 30 die from recurrent embolism. Anticoagulant Rx
  decreases mortality to lt 5

56
PATHOPHYSIOLOGY
DVT (CALF, ILEOFEMORAL SYSTEM, OR UPPER
EXTREMITY) PORTION OF CLOT BREAKS OFF AND TRAVELS
VIA IVC AND RIGHT HEART SYSTEM TO LODGE IN
PULMONARY CIRCULATION PORTION OF LUNG VENTILATED
BUT NOT PERFUSED (PHYSIOLOGIC DEAD SPACE) LEADING
TO HYPOXEMIA AND HYPERCARBIA COMPENSATORY
MECHANISMS (TACHYPNEA, INCREASED DEPTH OF
VENTILATION)
57
PATHOPHYSIOLOGY
IF SIGNIFICANT SIZED CLOT (gt50 OF VASCULAR TREE
INVOLVED), COMPENSATORY MECHANISMS FAIL, WITH
INCREASED PULMONARY VASCULAR RESISTANCE,
INCREASED RIGHT-SIDED HEART PRESSURES, AND
INCREASED V/Q MISMATCH PULMONARY HYPERTENSION,
ACUTE COR PULMONALE, DECREASED CARDIAC OUTPUT,
AND HEMODYNAMIC COLLAPSE
58
PATHOPHYSIOLOGY
IF INITIAL EVENT IS SURVIVED, CLOT RECANALIZES
OVER SEVERAL WEEKS CHRONIC PULMONARY
HYPERTENSION/COR PULMONALE DEVELOPS
59
Natural History

• Most pulmonary emboli are multiple, and the lower
  lobes are involved
• From deep veins of lower extremities
• Also pelvic, renal, upper extremity, right heart
  chambers
• Large thrombi lodge _at_ bifurcation of main PA or
  lobar branches -gt hemodynamic compromise
• Smaller thrombi occlude smaller vessels in
  periphery
• More likely to cause pleuritic chest pain
  (inflammatory response adjacent to parietal
  pleura)

60
Pathophysiology Review

• Normal RV has a narrow range over which it can
  compensate for acute increases in afterload. The
  pericardium has a limited ability to distend.
• Increased RV afterload -gt elevation in RV
  wall pressures -gt dilation and hypokinesis of
  the RV wall -gt
• shift of intraventricular septum towards left
  ventricle (tricuspid regurgitation) and decreased
  LV output.

61
Respiratory Consequences

• Early
• Increased alveolar dead space, Pneumoconstriction,
  hypoxemia, hyperventilation
• Late
• regional loss surfactant, pulmonary infarction
• Arterial hypoxemia frequent, not universal
• V/Q mismatch, shunts, reduced CO, intracardiac
  shunt via PFO
• Infarction uncommon bronchial arterial
  collateral circulation

62
PIOPED Sx

• dyspnea (73)
• pleuritic chest pain (66)
• cough (37)
• hemoptysis (13)

63
Physical Size Matters

• Acute PE (no infarct)
• Non-specific
• Tachypnea, tachycardia, pleuritic pain, crackles
  and local wheeze _at_ embolus site
• Multiple PEs
• Non-specific
• Pulmonary HTN and cor pulmonale
• High JVD, RV heave, palpable impulse 2nd LICS, RV
  S3 gallop, systolic murmur over the left sternal
  border that is louder during inspiration,
  hepatomegaly, ascites, dependent pitting edema.
• Massive PE
• Shock , hypotension, poor perfusion, tachycardia,
  and tachypnea
• Shock index HR/syst BP gt1

64
Physical exam

• Signs of pulmonary hypertension
• palpable impulse over 2nd LICS, loud P2, RV S3
  gallop, and a systolic murmur louder on
  inspiration at left sternal border (TR)
• Acute pulmonary infarction
• Decreased excursion of involved hemithorax,
  palpable or audible pleural friction rub,
  localized tenderness
• Signs of pleural effusion, hemoptysis, fever

65
Physical PIOPED

• Tachypnea (70)
• Rales (51)
• Tachycardia (30)
• Fourth heart sound (24)
• Accentuated P2 (23)
• Fever lt 39C ( 14) of patients (gt 39.5C not
  from PE)
• Palpable Chest wall tenderness w/o Hx trauma

66
CLINICAL FEATURES

• Symptom Percent
• dyspnea 73-84
• pleuritic chest pain 66-74
• apprehension 59
• cough 37-53
• leg swelling 28
• hemoptysis 13-30
• diaphoresis 27
• nonpleuritic chest pain 4-14
• syncope 13
• wheezing 9

67
CLINICAL FEATURES

• Sign Percent with sign
• tachypnea (RRgt20) 70
• rales 51-58
• accentuated P2 23-53
• tachycardia (HRgt100) 30-44
• temp gt 37.8 43
• S3 or S4 34
• thrombophlebitis 32

68
DIAGNOSIS ECG

• ECG most common non-specific ST T wave
  changes. 40 will have tachycardia (EM rap)
• Normal ECG not sensitive enough to R/O PE
• changes not specific for PE, and reflect signs of
  right heart strain
• new RBBB
• R axis deviation
• S1 Q3 T3
• others
• electrical alternans
• T wave inversion
• atrial fibrillation
• sinus tachycardia
• normal in 20-30 of cases

69
DIAGNOSIS CHEST X-RAY

• abnormal in gt80 of cases of PE (up to 30 N
  initially), but nonspecific findings
• atelectasis
• pleural effusion
• elevated hemidiaphragm (50 of initial CXRs of
  patients with PE)
• pneumonia-like infiltrates, especially w/i 3 days
  of symptom onset (33-50 of patients with PE)
• May mislead you to diagnosing pneumonia

70
DIAGNOSIS CHEST X-RAY

• other findings
• Hamptons hump
• wedge-shaped, pleural based infiltrate with apex
  toward hilum, representing lung infarction
• Westermarks sign
• peripheral oligemia secondary to clot
  interrupting blood flow
• this is the earliest detectable sign in PE, if
  present
• Fleishners sign
• large sausage-shaped pulmonary artery (some call
  this part of Westermarks sign)

71
DIFFERENTIAL DIAGNOSIS

• pneumonia costochondritis
• pneumothorax other emboli
• angina/MI sepsis
• pleurisy aortic dissection
• MSK injury pericarditis
• carcinoma anxiety/panic
• asthma/COPD CHF
• lung abscess

72
What if?

• 38 yo woman with burning substernal CP radiating
  to throat. Not pleuritic.
• 120/80 P-80 RR-18, normal sat, afebrile
• Mild mid-epig tenderness
• N ECG and CXR
• ?risk

73
What if?

• Rural ED
• 72 yo male
• fever, SOB, pleuritic CP x 2 days
• HR 110, bp 140/90, RR 22, sat 90
• CXR unremarkable
• Pre-test probability
• What test/Rx?

74
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. Pulsegt100/min 1.5
3. Immobilization bedrest (except access to BR) gt 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 lt2 LOW
0.12 2-6
MODERATE 1.90 gt6
HIGH 6.00
75
PRETEST PROBABILITY

• Can docs really assess pretest probability?
• while initial PIOPED study divided patients into
  low, moderate, and high probability with no
  clinical information, now algorithms
• lt10, 11-60, gt60

76
Standardized Clinical Assessment

• Geneva scoreclinical ABG CXR
• Well Criteria 6 clinical alternate dx
• Pisa-PED Sx, ECG, CXR
• Perrier 8 clinical, ABG or CXR

Clive Kearon. Diagnosis of pulmonary embolism.
CMAJ January 21, 2003 168 (2)
77
(No Transcript)
78

• Am J of Medicine 2002

79
"Excuse me. ... I know the game's almost over
but just for the record, I don't think my buzzer
was working properly.by Gary Larson
 
 
 
 
80
Quiz Controversies galore

• Age does not affect the d-dimer
• wrong specificity 67 50 yrs, 10 80 yrs
• Specificity of D-dimer decreases after surgery
• yes 7 inpatients vs 47 outpts
• Sensitivity of D-dimer decreases after 24 hrs of
  heparin
• yes 96 to 89
• D-dimer is useful in high probability pts
• only 28 specificity compared with 54 in low
  clin prob. High prevalence of PE means lower NPV
  - only 77 (comp with 100)
• Malignancy reduces the specificity of D-dimer
• yes 48 vs 82

81

• All d-dimers are created equal
• Kovacs 2001 sensitivities SimpliRED, Accuclot
  and il-Test were 79, 90 and 87
• False negative D-dimers are more common in those
  with sub-segmental PEs
• true
• The sensitivity of D-dimer increases if the clot
  has been there gt72 hrs
• false, circulating T1/2 is 8hrs so if no new
  clot forming

82
DIAGNOSIS D-DIMER

• Degree of elevation proportional to extent of PE
  (Kearon, CMAJ)
• If high sensitivity then low specificity (40)
  and high false (53)

83
Our test

• Calgary Vidas rapid ELISA assay
• Perrier Lancet 1999
• N918 followed up for 3 months after non-invasive
  protocol
• Normal in 31 of consecutive outpts with
  suspected DVT/PE
• For DVT 99.3 NPV (97.5, 99.9) Supposedly
  better for PE
• Negative predictive value of 100 for subsequent
  symptomatic venous thromboembolism.

84

• Low clinical prob and negative sensitive D-dimer
  99 negative predictive value for PE
• Safe method of exclusion Wells and de Groot
• Non-diagnostic V/Q (lthigh) neg D-dimer
  negative predictive value of 97 ? considered
  non-diagnostic esp if clinical prob high

85
DIAGNOSIS BLOOD TESTS

• A-a gradient (Alveolar-arterial 02 gradient)
• gradient PA02 - Pa02
• measure of gas exchange
• Fi02 (barometric pressure - 47 mm Hg) -
  1.25(PC02) - Pa02
• normal limit age/4 4 (NB never zero because
  gas exchange is imperfect)
• normal A-a gradient and PC02 gt 36 mmHg 98 NPV
  for PE
• very nonspecific (any pulmonary disease process
  can increase the A-a gradient)
• patients with small PEs usually have no change
  in the gradient other than that expected for age

86
Algorithm for suspected PEWells. Ann Int Med,
2001
87
Non -Invasive Testing

• NEED TO Dx PE as HIGH MORTALITY IN THOSE NOT Dx
  or MISDIAGNOSED!
• Angiography carries risk
• Mortality 0.5, invasive, labour intensive
• Can make Dx without P. angio

Clive Kearon. Diagnosis of pulmonary embolism.
CMAJ January 21, 2003 168 (2)
88
DVT in PE

• 75 of pts with PE have DVT 2/3 prox veins
• Up to ¼ of pts with symptomatic PE have clinical
  evidence of DVT
• If less extensive PE then less likely to have
  prox DVT

Clive Kearon. Diagnosis of pulmonary embolism.
CMAJ January 21, 2003 168 (2)
89
DIAGNOSIS ULTRASOUND

• when a patient with known DVT has symptoms of PE,
  further diagnosis of PE is not necessary as
  treatment is similar
• therefore, lower extremity ultrasound does have a
  role in the workup of patient with PE
• If its negative DONT STOP 40 still had PE
  (Turkstra)
• AAFP lt50 have signs/sx in legs and in
  (Turkstra) one study lt30 had doppler

90
U/S

• venography 75 sensitivity for PE
• compression U/S 50 sensitivity for PE
• Among pts with nondiagnostic V/Q U/S is in 5
• Becomes in 2 on repeat U/S
• Consider venography in pts who are more likely to
  have a false-positive result
• Indeterminate U/S
• Previous DVT with potential for residual abN
• Negative D-dimer
• (Kearon)

91
Remember

• 50 of symptomatic PE lobar / main pulm
  arteries
• 20 are in subsegmental arteries (Kearon, CMAJ)

92
Quiz V/Q

• Age does not affect the accuracy of a lung scan
• Wrong More non-diagnostic (58 80 yrs) vs (32
  40 yrs)
• The proportion of non-diagnostic scans in COPD
• 71, 81, 91
• Previous PE increases PPV of a high prob VQ scan
• no, decreases it from 91 to 74

93
DIAGNOSIS V/Q SCAN

• perfusion scan
• injection of radiolabeled dye (Tc99)
• most information obtained from perfusion scan
• ventilation scan
• inhalation of radiolabeled aerosol (Tc99 or Xe
  gas)
• divided into normal, low, intermediate, and high
  probability based upon presence/absence of V/Q
  mismatch
• Perfusion defects are non-specific (1/3 of
  defects PE) Increased probability of PE with
  increased size number, wedge shape, normal vent
  scan.

94
POSTTEST PROBABILITY OF PE WITH COMBINATION OF
CLINICAL SUSPICION AND V/Q SCANNING (PIOPED)
CL I N IC A L P R O B.
SCAN NORMAL LOW INT. HIGH HIGH 40 66
96 MOD. 6 16 28 88 LOW 2 4 16 56
95
VQ scan (from EM rap)

• Must be used with pre-test probability
• Low pre-test low prob VQ low prob (1-2)
• High and high (96)
• Very useful if concordant
• Relatively low radiation and no dye load
• Poor accessability at night, sending them away
• Near useless in COPD/ CHF indeterminate
• More useful if normal CXR (otherwise consider
  spiral CT)

96
If indeterminate

• High prob scans in 50 of pts with PE and 10 of
  pts tested for PE
• 1/3 of pts tested for PE N scans
• therefore 65 of pts with suspected PE have
  intermediate or low prob scans
• Continue on to pulmonary angiogram or another
  test
• More likely that PE is in subsegmental pulmonary
  artery (20 of symptomatic PE)
• Consider the label of PE and further workups
  every time the pt is SOB, insurance problems
• 6 mos 1 risk of signif bleeding over 1 yr

97
When the testing is indeterminate

• Prevalence of PE of 20
• Too high to ignore and too low to treat (although
  some would)
• Can do pulm angiography OR U/S

98
Spiral CT
99
DIAGNOSIS SPIRAL CT

• more sensitive for large central than small
  peripheral/subsegmental (gt 4th generation
  vessels) emboli (86 vs. 63)
• role in establishing diagnosis unclear at present
• ? after V/Q scan and negative doppler U/S
• ? after V/Q scan
• ? instead of V/Q scan

100
Diagnostic Imaging for PESpiral CT

• Plain CT (without dye bolus and look at pulm
  vasculature) not sensitive at all
• IV contrast, direct visualization
• subsegmental PE not well seen
• more specific, underlying lung dx
• sens depends on CT, experience
• wide variation in studies
• De Monye Sens 69 spec 86
• Only 21 for subsegmental PE
• Rathbun. Ann Intern Med, 2000 (review)
• sens 53-100, spec 81-100

101
Spiral CT

• Perrier. Ann Intern Med, 2001
• sens 70, spec 91 , 4 inconclusive
• PE rate on F/U is lt5 after N CT angio with
  D-dimer
• good interobserver agreement
• Combined results
• sensitivity for subsegmental PE is 30
• accounts for 20 of symptomatic PE
• substantial risk of recurrence
• normal CT alone does not exclude PE
• (Kearon)

102

• Algorithms that incorporate helical CT require
  further validation.
• role?
• no evidence to withhold Rx if CT negative
• Ability to reveal alternative pulmonary dx
• CT/ MRI may replace angiography
• CT venography
• benefit over U/S not determined

103
Echo

• 50 of pts diagnosed with PE have echo evidence
  of right ventricular dysfunction at presentation,
  
• Marker of occult hemodynamic instability
• associated with an elevated short-term
  mortality (Kearon, CMAJ)

104
Diagnostic Imaging in PEEchocardiography

• useful for patients in shock/arrest
• r/o DDx tamponade, Ao dissection, AMI
• May see embolized thrombi in R heart or central
  pulm arteries
• indirect evidence of PE
• RV overload, septal shift to L, TR, ? PA
  pressure, RV wall motion abn
• Sensitivity 50 and specificity 90 for PE
• Because of low sensitivity not suitable as
  routine diagnostic test

105
Diagnostic Imaging in PEEchocardiography

• useful for patients in shock/arrest
• r/o DDx tamponade, Ao dissection, AMI
• indirect evidence of PE
• RV overload, septal shift to L, TR, ? PA
  pressure, RV wall motion abn
• sub-massive PE independent predictor of
  mortality (?significance)

106
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107
Diagnostic Imaging for PEPulmonary Angiography

• Gold standard (imperfect)
• sens 98, spec 95-98
• pigtail catheter inserted into the R and L
  pulmonary arteries (as well as their branches)
  with injection of contrast dye
• Can be prelude to catheter fragmentation to
  reduce clot burden.

108
DIAGNOSIS PULMONARY ANGIOGRAM

• Angiography preferred when
• Segmental intraluminal filling defect on helical
  CT
• Subsegmental intraluminal filling defect on
  helical CT and high clinical prob of PE
• High prob V/Q scan and low clinical suspicion
• Serial testing not feasible (eg, pts scheduled
  for surgery or geographic inaccessibility)
• Otherwise consider serial U/S

109
DIAGNOSIS PULMONARY ANGIOGRAM

• ED physicians reluctant to use
• invasive, risks (0.5 mortality), requires
  expertise, not readily available, time consuming,
  , contra-indicated in renal impairment (1 renal
  failure)
• Limitations
• difficult to diagnose emboli in 3rd order
  (lobular) or smaller arteries
• smaller emboli are the precursors to massive PE
• false positives with intraluminal tumors or
  extrinsic masses
• 0.5-1 mortality (anaphylactoid reactions,
  dysrhythmias, cardiac arrest, endocardial
  injury/perforation)
• 1 with N angiogram have PE w/i a few mos
  (Tintinalli)

110
LOW PROBABILITY PE
D-Dimer
Neg
Positive
VQ Scan
STOP
Normal
Non-high
High
STOP
CUS legs
Pulm Angio
DVT
Normal
Positive
Normal
CUS In 1 week
TREAT
STOP
TREAT
111
MODERATE PROBABILITY PE
D-Dimer
Neg
Positive
VQ Scan
STOP
Normal
Non-high
High
CUS legs
TREAT
DVT
Normal
CUS In 1 week
TREAT
Pulm Angio
OR
112
HIGH PROBABILITY PE
VQ Scan
Normal
Non-high
High
CUS legs
TREAT
Pulm Angio OR
OR Pulm Angio
Normal
DVT
CUS In 1 week
Pulm Angio OR
TREAT
113
Clive Kearon. Diagnosis of pulmonary embolism.
CMAJ January 21, 2003 168 (2)
114
Some numbers

• Low PTP neg D-dimer NPV of 99-100
• Non-diagnostic scan negative D-dimer normal
  U/S NPV 98
• Non-diagnositic lung scan negative D-dimer
  NPV of 97 (keep going)
• Non-diagnostic scan normal U/S NPV 95
• There is evidence that pts with these results
  have a low (lt2 risk of presenting with
  symptomatic venous thromboembolism during follow
  up)
• Some will still choose to do serial testing
  anyway

115
Algorithm for suspected PEWells. Ann Int Med,
2001
116
Wells AlgorithmCriticism

• Uses SimpliRED assay lower sens.
• NPV for clinical prob D-dimer 99.5
  (99.1-100)
• spiral CT not included
• could replace angiography?
• Low prevalence of PE (9)
• not validated by other RCTs

117
If CT instead, stop if large Pulm A or segmental
Angio or CT if low prob
/- venography
Venography/CT if high susp, severe sx or poor
cardiopulm reserve
118
(No Transcript)
119
Treatment Goals

• reduce mortality
• prevent extension/recurrence
• restore pulmonary vascular resistance
• prevent pulmonary hypertension

120
Treatment

• Without tx, 50 of symptomatic prox DVT or PE
  are expected to have recurrent venous
  thromboembolism within 3 mos.
• With tx of PE, 50 resolution of perfusion
  defects is expected after 2-4 wks.
• Eventually , complete resolution of PE expected
  in 2/3 of pts. (Kearon , CMAJ)
• Significant long-term nonresolution of emboli
  causing pulmonary HTN or cardiopulmonary symptoms
  uncommon

121
Treatment (from EMrap)

• IV heparin use weight-based protocol
• 5000 U bolus (80 U/kg) and then 1280 U/hr (18
  U/kg/hr) drip for average 70 kg man
• Max 40,000 /day and 15,000 bolus (EMrap)
• Start coumadin on day 1 if VTE confirmed

122
TREATMENT

• heparin (UFH or LMWH) X 4-5 days
• currently IV UFH is still used locally for
  initial treatment

123
Treatment of VTEAnticoagulation

• Out-patient LMWH
• LMWH superior to UFH? (Gould 1999)
• out-pt Rx safe in PE (Kovacs, 2000)
• DVT start Rx, definitive test in 24hr
• baseline B/W

124
LMWH (EM rap)

• No lab monitoring, decreased hospitalization and
  complication for DVT
• Approved for documented DVT PE
• 1 mg/kg BID Enoxaparin
• Dalteparin and Tinzaparin
• Arch of Int Med 2000 PE tx
• Lower recurrence risk of PE and lower rates of
  major bleeding
• With LMWH as initial tx and oral anticoagulation
  for INR of 2-3, rate of major bleeding at 3 mos
  is 3 and mortality is 0.5 (BTS)

125

• 1) Can LMWH alone be given from the start or do
  you need a bolus of UFH (most studies)
• 2) Are the various LMWHs equivalent?

126
Anticoagulation

• Enoxaparin 1mg/kg bid or 1.5 od
• Tinzaparin 175 anti-Xa u/kg od
• start warfarin 5mg on day 1
• d/c LMWH when INR gt2.0 x 2 days
• Rx 3 mos if 1st and reversible cause
• 6 mos if non-reversbile
• indefinite if recurrent, CA, genetic

127
SPECIAL CONSIDERATIONS

• One shot heparin and imaging in the morning
• after hours DI difficult to obtain
• safety of single dose LMWH with U/S the next day
  established and now common practice (Bauld et al.
  Am J Emerg Med 1999 17 11-15)
• the above study looked at 128 patients, 44
  test, 84 neg
• Followed for 3 months after dalteparin
• No serious adverse effects

• Bauld DL, Kovacs MJ. Dalteparin in Emergency
  Patients to Prevent Admission Prior to
  Investigation for Venous Thromboembolism.
  American Journal of Emergency Medicine. 1999 17
  (1) 11-14

128
Treatment of PECriteria for admission

• Hemodynamic instability
• O2 requirement
• surgery lt 48hr
• risk of active bleeding
• history of HIT
• IV pain control

129
THROMBOLYTICS

• indications
• shock/hemodynamic instability
• exhausted cardiopulmonary reserve
• hypoxemia or hypotension
• severe comorbid illnesses (prev. lobectomy,
  cardiomyopathy, other cardiopulm. disease)
• high likelihood of recurrence
• helps prevent chronic cor pulmonale from
  recurrent emboli with incomplete recanalization

130
Thrombolytics

• no evidence of mortality benefit
• including in cardiac arrest (case series)
• No benefit of intrapulm infusion
• protocols
• t-PA 100mg over 2 hr
• SK 250,000U over 30min 100,000 x 24h
• (UK 4400U/kg over 10min rpt x 12-24hr)
• arrest t-PA 10mg/kg bolus x 2 q 30 min

131
Treatment of massive PEThrombolytics

• no benefit in hemodynamically stable
• Including those with RV dysfunction on echo
  (evidence not there yet)
• 5-10 major bleed, 1-2 ICH

132
Embolectomy

• Indicated in acute, massive PE if
• contraindication to thrombolytics
• unresponsive to medical mgt sustained
  hypotension
• moribund pt ? poor results
• no evidence cf. with thrombolytics
• percutaneous vs. surgical
• ?role

133
IVC Filters

• Indications
• contraindication to anticoagulation
• recurrent VTE despite anticoagulation
• after surgical embolectomy
• no long term adv vs. anticoagulation
• anticoagulate if no contraindications
• Decousus 1998 RCT for prox DVT
• Not good
• Effective for the first 12 days but no
  improvement in short or long term mortality
• At 2 yrs, the recurrence of DVT greater in the
  IVC group

134
What if?

• 50 yo pt diagnosed 2 weeks ago with DVT/PE and
  has been on warfarin
• Returns today with palpitations
• ?
• Check INR, HR, sat, leg-swelling,
• Ask re dyspnea, hemoptysis
• In general, do the test that proved the VTE the
  first time (U/S and IPG may be false )

135
What if?

• 450 lb male with pleuritic chest pain and dyspnea
• ?
• May be too large for CT/ VQ/ MRI
• D-dimer, U/S, look for alternate dx
• Consider empiric anticoagulation
• No good evidence for this
• Difficult to dose LMWH, some docs exceed
  recommended limit.

136
What if?

• 30 yo 3rd trimester woman with pleuritic CP
• What considerations?

137
Pregnancy

• Modifications
• D-dimer ? in pregnancy
• Start with U/S if then tx
• gravid uterus compresses the IVC, thereby
  changing Doppler flow in the lower extremities.
• V/Q safe, no breastfeed x 15hr post
• If angiography use brachial approach with abd
  screen
• No safety data for spiral CT try to avoid

138
DIAGNOSIS V/Q SCAN

• radiation from complete scan 50 mrad (5 chest
  X-rays) most of which comes from ventilation scan
• toxic dose of radiation for a fetus 5 rad
• in pregnancy, modifications include
• full V/Q scan with different radiolabeling agent
  (sulfur colloid) for ventilation scan to decrease
  fetal absorption (preferred regimen in Calgary)
• full dose perfusion scan with ventilation scan as
  needed the following day (if normal perfusion
  scan, no need to persist with ventilation scan)
• 1/2 dose perfusion scan followed by same day 1/2
  dose ventilation scan (results in grainy images)

139
Pregnancy

• MRI helpful
• Risk of inaccurate dx of PE in pregnancy exceeds
  the risk of radiation exposure with dx testing.
• LMWH in DVT, not studied in PE
• PE UFH IV x 4-5 days, then s/c
• treat x 3 months or 6 weeks postpartum (whichever
  is longer)
• switch to oral postpartum (OK for breastfeeding)

140
The end Questions?
141
Thanks to

• Rhonda Ness
• Rob Hall for interesting questions
• Slides from Denise Watt, Mark Yarema, Tony Chad

142
References

• Anand SS, Wells PS, Hunt D et al. Does This
  Patient Have Deep Vein Thrombosis? JAMA 1998
  279 1094-1099.
• Ault M. Upper Extremity DVT What Is the Risk?
  Arch Intern Med. 1998 Sep 28158(17)1950-2.
• Bauld DL, Kovacs MJ. Dalteparin in Emergency
  Patients to Prevent Admission Prior to
  Investigation for Venous Thromboembolism.
  American Journal of Emergency Medicine. 1999 17
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• British Thoracic Society Standards of Care
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143
More references

• Kearon C. Diagnosis of pulmonary embolism. CMAJ
  January 21, 2003 168
• Kovacs MJ, MacKinnon KM, Anderson D, et al. A
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  diagnosis of venous thromboembolism. British
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• Niemann JT. Diagnostic Accuracy of a Bedside
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  for Rapid Exclusion of Pulmonary Embolism A
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• Perrier A, Desmarais S, Miron M-J et al.
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  Investigation of Pulmonary Embolism Diagnosis.
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• Prandoni P, Polistena P, Bernardi E, et al
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• Prandoni P, Polistena P, Bernardi E, et al.
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• Randolph AG, Cook DJ, Gonzales CA. Benefit of
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• Tintinalli JE, Kelen GD, Stapczynski JS.
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• Wells PS, Anderson DR, Rodger M et al. Excluding
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• http//images.google.ca/imgres?imgurlwww.physweek
  ly.com/picts