Transcript 1400_OConnell_EB4E5x

Management of Pulmonary
Embolism: Incidental PE
Casey O’Connell, MD
Associate Professor
Jane Anne Nohl Division of Hematology
Department of Medicine, Keck School of Medicine
USC
OBJECTIVES
• Define the incidental pulmonary embolism (IPE) and
explain why its prevalence is increasing
• Outline an approach to the clinical evaluation of a
patient with IPE
• Identify the factors that confer greater clinical
significance to the IPE
• Develop an approach to the isolated subsegmental PE
that is incidentally detected on MDCT of the chest
Incidental Pulmonary Embolism: Defined
Silent PE
• 1 or more pulmonary
arterial filling defects
identified on a contrastenhanced CT scan that is
ordered for reasons
other than “rule-out PE”
INCIDENTAL
PE
IPE
Unsuspected
PE
Asymptomatic
PE
Incidental Pulmonary Embolism: Prevalence
and Risk
• Highest mean prevalence = INPATIENTS (4%)
• Cancer Patients (3.1%)
• Increased risk with:
• Age
• History of PE
• Smaller slice thickness
• More proximal location of PE
Dentali et al. Thromb Res 2010;125:518-22.
INCIDENTAL DETECTION OF PULMONARY EMBOLI:
A FREQUENT FINDING IN CANCER PATIENTS
• Single row detector scanners:
• Retrospective: 1% (55% of PE were in cancer patients)
Winston CB et al. Radiology 1996; 201: 23-27.
• Prospective: (1.7% in cancer patients and 9% for hospitalized cancer patients)
Gosselin MV et al. Radiology 1998; 208:209-215
• Multi-row detector scanners:
• Retrospective: 3.4% (Prevalence of malignancy for unsuspected PE was greater;
64.7% vs. 35.3%, p<0.05%)
• Storto ML et al. AJR 2005; 184: 264-267.
• Prospective: In 385 chest CT in cancer patients, 10 (2.4%) incidental PE were
detected.
Sebastian AJ, Paddon AJ. Clin Radiol 2006; 61: 81-85.
Incidental Pulmonary Embolism: Radiographic
Features
64-MDCT
• Smaller slice
thickness leads to
better visualization
of the pulmonary
arterial tree
MORE IPE
0.5mm
16-MDCT
1.5%
0.625mm
4-MDCT
2.5mm
SDCT
4mm
Patel et al. Radiology 2003. Dentali et al. Thromb Res 2010;125:518-22
Incidental Pulmonary Embolism: Radiographic Features
in 92 patients
MAIN,R,L
LOBAR 29%
29%
Segmental 36%
Subsegmental 6%
No difference in distribution when compared to
408 patients with symptomatic PE.
Schteinberg et al. Respiration 2012;84:492-500.
Where Do Incidental PE Occur In Cancer
Patients?
50%
Browne et al. J Thoracic Oncol 2010;5:798-803
Main
7 (10%)
Lobar
26 (37%)
Segmental
20 (29%)
Subsegmental
17 (24%)
•O’Connell CL et al. JTH 2011: 9:305-311
47%
IPE: Reliability of Radiologic Diagnosis can be
affected by PE location
• Excellent inter-observer agreement (96.7%) for IPE
diagnosed in 62 cancer patients1
• Only 1 had SSPE
• In a blinded review of IPE in 70 cancer patients including
known negative studies in another CT scans from 140
matched cancer controls there was a 100% concordance.2
• Among community radiologists, 15% false positive
diagnosis of SSPE.3
• 50% of these due to respiratory motion artifact
• Another 27% were indeterminate
• Vascular lesions with short axis <6mm more likely to be false positive or
indeterminate
1. DenExter et al. Thrombosis Res 2015.
2. O’Connell CL et al. JTH 2011: 9:305-311
3. Miller et al. Ann Am Thor Soc 2015.
Does the pulmonary arterial segment involved
have prognostic significance?
• Incidentally found subsegmental PE (SSPE) may be
associated with less recurrence, death
• Few, small reports of untreated non-cancer patients
with SSPE who have excellent short-term outcomes
• Even among cancer patients, survival does not
appear to be adversely impacted by SSPE
Carrier M et al. JTH 2010; 8:1716-22.
Donato AA et al. Thromb Res 2010; 26(4):e266-70 .
Van der Hull et al. JTH 2016; 14: 105-13
PATIENTS WITH PROXIMAL INCIDENTAL PE HAVE A WORSE
PROGNOSIS THAN MATCHED CANCER CONTROLS
O’Connell CL et al. JTH 2011: 9:305-311
Patients with IPE have PE-related signs and
symptoms.
• Majority of IPE patients with and without cancer have
symptoms
• Respiratory symptoms like DOE, cough, SOB, chest pain and
fatigue
• Not all studies investigate symptoms reported prior to
diagnosis
• Symptoms correlate with poorer survival among
cancer patients with IPE
• Age- and Stage-Matched controls without IPE had
significantly less fatigue, better survival
Schteinberg et al. Respiration 2012.. O’Connell et al.
JCO 2006. O’Connell JCO 2011.
PROPOSED ALGORITHM FOR APPROACHING
THE INCIDENTAL SUBSEGMENTAL PUMONARY
EMBOLISM
• Suggestions only, not a validated tool
• False positive diagnoses of SSPE may be as high as 15-40%
• Clinician must weigh: risk of clot progression vs risk of
bleeding
• & Note radiation exposure, concurrent therapies
ISSPE
NO
CANCER?
DVT
PRESENT?
YES
NO
SYMPTOMS?
YES
TREAT WITH
AC
YES
ISSPE: Proposed Algorithm, part 2
ISSPE:
NO DVT
NO CANCER
NO SYMPTOMS
HIGH BLEED
RISK
Consider F/UP
CTPA D-DImer
POSITIVE
TREAT WITH
AC
LOW BLEED
RISK
NEGTIVE
NO AC
OR
Consider AC
PE: Initial Management
• On objective diagnosis or high clinical suspicion of DVT, start therapy
with (Grade 1A):
• SC LWMH (assuming normal renal function)
• SC Fondaparinux (5mg, 7.5mg, 10mg)
OVER (Grade 2B/C)
• IV UFH (bolus 5000U f/b 18U/kg/hr)
• SC UFH (bolus 333U/kg, 250U/kg BID unmonitored, bolus 17,500U
or 250U/kg then adjust)
• Start Oral VKA same day with overlap at least 5 days and until INR > 2
x 24 hours (Grade 1A)
ACCP Guidelines. Chest
PE: Initial Outpatient Management
• Level 1 evidence for safety of treating DVT with outpatient LMWH vs.
inpatient UFH followed by OAC
• No difference in outcomes
• Many pts excluded; all but 3 excluded PE
• Incorporated in ACCP Guidelines
• 9/10 studies with cost data suggest outpatient LMWH cheaper
• 2012 guidelines recommend daily over twice daily LMWH if daily dose
is twice that of bid dosing (????!)
ACCP Guidelines. Chest 2008:133S, 2012
Segal et al. AIM 2007;146:211.
DOACs for Venous Thrombosis
Rivaroxaban
• 15 mg bid. for 3
weeks
• then 20 mg once
daily
• Can be
used
as monotherapy
Dabigatran
• 150 mg bid
• 5 days of
parenteral
treatment needed
before dabigatran
Apixaban
• 10 mg bid for 7
days
• then 5 mg b.i.d.
• Can be
used
as monotherapy
Edoxaban
• Daily (60 mg qd; or 30
mg for CrCl 15-49
mL/min or
weight<60kg or strong
P-gp inhibitors)
• 5 days parenteral
treatment needed
before edoxaban
FDA Approval Status (for VTE)
Approved for acute
treatment and long-term
prevention
Approved for acute
treatment and long-term
prevention
Approved for acute
treatment and long-term
prevention
Approved for acute
treatment Jan. 2015
IPE: Unanswered Questions
• Almost all clinical outcome data is retrospective
• Many studies do not report on presence of PE-related
symptoms
• There are no data, little guidance as to duration of
therapy
SUMMARY
• Incidental PE involving the main, lobar and segmental
arteries is clinically relevant and generally merits
anticoagulation therapy.
• Incidental PE in cancer patients is frequently associated with
symptoms which are often missed by the treating physician.
• Incidental PE has the same risk of recurrence and similar
impact on cancer prognosis as symptomatic PE.
• Truly asymptomatic patients, especially with ISSPE, may be a
distinct clinical group with a better prognosis
• In clinical trials the finding of an incidental VTE should be
considered a primary outcome event.