Download Venous Thromboembolic Disorders

Pulmonary Embolism
Larissa Bornikova, MD
July 21, 2006
Objectives
• To know the spectrum and sequelae of VTE
• To review the risk factors for VTE
• To understand the decision paradigms in the diagnosis of
PE
• To develop a systematic approach to evaluating a patient
with suspected PE
• To outline the initial treatment strategies for PE
Epidemiology
• Incidence of VTE is about 1 in 1000 per year.
• DVT and PE should be considered part of the same pathological
process.
- 40% of patients with DVT have asymptomatic PE on lung scanning.
- 29% of patients with PE have abnormal LE venous ultrasound.
• More than 500,000 patients are diagnosed with PE annually in the
United States. More than half of all patients with PE remain
undiagnosed.
• Mortality rate is up to 30% without treatment primarily due to
recurrent embolism.
• Therapy with anticoagulants decreases the mortality rate from PE to 28%.
• Sudden death is the presenting clinical manifestation in nearly 25% of
patients with PE.
Sequelae of VTE
• Pulmonary embolism
- flow obstruction → increased pulmonary vascular resistance →
redistribution of blood flow → V/Q mismatch due to alveolar dead
space → increased RV afterload and RV wall tension → RV dilatation,
dysfunction and possible ischemia. If ASD or PFO present R → L
shunting and paradoxical embolism may occur.
- other clinical sequelae: chronic dyspnea, chronic pulmonary
hypertension (<2%), right-sided heart failure, death
• DVT
- post-thrombotic syndrome in 25% (swelling, stasis dermatitis,
ulceration, venous insufficiency and venous claudication)
- paradoxical embolism/stroke
- PE
Risk factors
Understanding risk factors will increase likelihood that DVT
and PE will be diagnosed and/or prevented.
• Think of Virchow’s triad:
venous stasis, endothelial damage, and hypercoagulable
state.
• Think of risk factors as modifiable and non-modifiable
(important when considering cause of VTE and duration or
therapy).
Risk factors (cont’d)
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Immobility or prolonged travel
Increasing age
Obesity
Cigarette smoking
OCPs (including progesterone
only pills)
Pregnancy
HRT
Tamoxifen
Stroke/limb paresis or paralysis
Trauma
Surgery
PNH
Nephrotic syndrome
Previous PE or DVT
Varicose veins
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Cancer
Congestive heart failure
COPD
Diabetes
Inflammatory bowel disease
Antipsychotic drug use
Chronic indwelling central
venous catheters
Permanent pacemaker/ICD
Polycythemia Vera / ET
Inherited Thrombophilias (see
next slide)
Acquired Thrombophilias (APS
and LA)
Hyperviscosity (myeloma,
Waldenstrom’s)
High concentrations of factor
VIII or XI
Inherited Thrombophilias
Inherited Thrombophilias
Prevalence in
general population
Factor V Leiden
heterozygous 1% - 15%
homozygous ~ 1%
0.7 – 6.5 %
1 : 200 to 500
1 : 1000 to 5000
1 : 2000 to 5000
Prothrombin gene mutation
Protein C deficiency
Protein S deficiency
Antithrombin III deficiency
* Martinelli, et al. Blood 1998
Relative Risk
of thrombosis
7
80
2.8
7.3 *
8.5 *
8.1 *
Case I
CC: Shortness of breath
HPI: MV is a 40-year old woman, chemical manufacturing
executive, who comes to the Emergency Department with
complaints of shortness of breath, right sided chest pain
aggravated by breathing and coughing. Within the last week
she has returned from an overseas trip to China. She has not
noticed fever, chills or sputum production.
PMH: No recent surgeries; no prior hospitalizations or serious illnesses
Allergies: None
Medications: MVI, Orho-Novum 1/50 for excessive menstrual bleeding
Social History: No tobacco, alcohol, IVDU
Clinical Presentation
• What is the most common symptom of PE? What are other symptoms
of PE?
Dyspnea (>70%), pleuritic chest pain, cough, hemoptysis, syncope,
hypotension, PEA, but can be asymptomatic
• What are the signs you may find on physical exam?
Tachypnea, rales, tachycardia, loud P2, fever, pleural rub, hypotension,
increased JVP, right-sided S3, parasternal lift, cyanosis.
• What are the radiographic signs of PE?
Normal CXR, Westermark’s signs, Hampton’s hump, Palla’s signs,
pleural effusion.
• What are the EKG findings?
Sinus tachycardia, S1Q3T3, RAD, RBBB, T-wave inversion in V1V4.
• What will you see on ABG?
Respiratory alkalosis, hypoxemia, widened A-a gradient.
Case I (cont’d)
Physical exam:
BP 100/70 P 95 (recumbent)
BP 95/80 P 120 (upright)
RR 24 T 98.9
HEENT: WNL
Chest: decreased breath sounds at the R base
Cardiac: tachy; normal heart sounds; no m/r/g
Abdomen: soft, NABS, NT, ND, no HSM
Extremities: warm, w/o cyanosis, clubbing or edema
CXR: ill defined pleural-based infiltrate at the fight posterior
base
Labs: ABG 7.49/29/80 (room air)
WBC 10.2; Hgb 13; Hct 37; Plt 238,000
Approach to the patient with suspected PE.
Clinical suspicion for PE should lead to diagnostic evaluation.
Two steps:
• To determine the patient’s clinical probability of PE.
• To decide what diagnostic test you would you like to order.
EKG, blood gases, CXR may help determine the pretest
probability and focus the differential diagnosis.
Well’s Criteria
Validated clinical risk factors that help to determine pre-test probability of
a PE in outpatients who present to ED .
Risk factor
No. of points
Clinical signs and symptoms of DVT
An alternative diagnosis less likely than PE
Heart rate >100 beats/min
Immobilization or surgery in the previous 4 wks
Previous DVT or PE
Hemoptysis
Cancer (receiving treatment, treated in past 6 mo,
or palliative care)
3.0
3.0
1.5
1.5
1.5
1.0
1.0
Patients can be classified into three groups on the basis of clinical
probability of PE:
Low (<2 points) prevalence 10% or less
Intermediate (2-6 points) prevalence of about 30%
High (> 6 points) prevalence of 70% or more
Case I (cont’d)
 What is the probability that this patient
has a pulmonary embolism?
 What diagnostic test would you like to
order?
Diagnostic Approach to a Patient with an Intermediate Clinical Probability of Embolism, Using
Helical CT Scanning or Ventilation-Perfusion Scanning as the Initial Diagnostic Study
Fedullo P and Tapson V. N Engl J Med 2003;349:1247-1256
Diagnostic tests
EKG, blood gases, CXR may help to determine the pretest
probability and focus the differential diagnosis.
Diagnostic tests:
• D-dimer
• Imaging. Spiral CT with IV contrast vs. V/Q scan vs.
pulmonary angiography
• Echocardiogram (poor diagnostic test)
Treatment of acute PE: Risk stratification
Prognostic tests:
• Echocardiogram (RV dysfunction signifies increased risk
of death during hospitalization).
• BNP
• Troponin (high risk of complicated hospital course)
Adverse outcome also predicted by: cancer, heart failure,
previous DVT, hypotension, hypoxemia, DVT on US.
Case I (cont’d)
How would you treat this patient?
a. LMWH followed by warfarin
b. IV heparin followed by warfarin
c. Thrombolytic therapy
d. Warfarin alone
Treatment of acute PE
• Unfractionated heparin
• LMWH
• Warfarin
- initiate 5 mg rather than 10 mg 88% vs. 53% therapeutic on day 5
(Crowther et al Arch Intern Med 1999)
• Thrombolysis
• Pulmonary embolectomy or catheter thrombus extraction
• IVC Filter (contraindication to AC, recurrent PE while on
AC, complication of AC, poor cardiopulmonary reserve)
- at 8 years fewer symptomatic PE (6 vs. 15%) but more DVT (21 vs.
12 %) (PREPIC trial Circulation 2005)
Duration of treatment of acute PE
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Transient risk factors → 3 – 6 months
First VTE, idiopathic → 6 – 12 months
VTE + irreversible risk factor → 1 year to lifelong
Recurrent → lifelong
Testing for inherited and acquired thrombophilia
- AT III level depressed by heparin; Prot C and protein S level lowered
by warfarin
Age-appropriate cancer screening
References
• Goldhaber, SZ. Pulmonary Embolism. Lancet 2004; 363: 1295 – 1305.
• Goldhaber, SZ. Pulmonary Embolism. N Engl J Med 1998; 339: 93 –
104.
• Fedullo, PF and Tapson VF. The Evaluation of Suspected Pulmonary
Embolism. N Engl J Med 2003; 349: 1247 – 1256.
• UpToDate
• Summary of the Seventh ACCP Conference on Antithrombotic and
Thrombolytic Therapy. Chest 2004; 126.
• Piazza G and Goldhaber, SZ. Acute Pulmonary Embolism Part I:
Epidemiology and Diagnosis. Circulation 2006; 114; 28 – 32.
• Piazza G and Goldhaber, SZ. Acute Pulmonary Embolism Part II:
Treatment and Prophylaxis. Circulation 2006; 114; 42 – 47.