Download Thromboembolic Events

Thromboembolic Events
Rodolfo M. Pascual, MD, FCCP
COI
 I have no conflicts to disclose related to this
presentation.
 "The detachment of larger or smaller
fragments from the end of the softening
thrombus which are carried along by
the current of blood and driven into
remote vessels. This gives rise to the
very frequent process on which I have
bestowed the name of Embolia."
Rudolf Virchow
(1821 –1902)
Venous Thrombolism-Virchow’s Triad
Stasis
Hypercoagulable
State
Endothelial injury
Thrombosis
Topics
 Venous Thromboembolism
 Prevention
 Diagnosis
 Management
 Venous thrombosis
 Superficial
 Deep
 Pulmonary embolism
 Acute
 Chronic
 Massive, submassive
Superficial vein thrombosis
 Confusing terminology
 Phlebitis
 SVT-Superficial vein thrombosis
 Superficial femoral vein is a deep vein but is often
mistaken for a superficial vein
 Bundens WP, JAMA. 1995;274(16):1296.
 SVT increases the risk for subsequent DVT and PE
 Van Langevelde K, Blood 2011,118:4239-41.
 SVT>5 cm long in lower limb, treat with LMWH
(prophylaxis doses) or fondaparinux 2.5 mg for 45 d
Case 1
 A 45 year old man with a history of diabetes mellitus
presents with unilateral leg swelling.
 There is no prior personal nor family history of DVT
or PE.
 There has been no injury, or surgery in the last year.
 There is some tenderness and warmth over the
superior aspect of the calf.
 The entire leg distal to the knee is swollen and warm
Questions for consideration
 What is the most appropriate initial diagnostic test?
 If the test is positive how should the patient be
treated?
 How long should the patient be treated?
Risk Factors
 More than 48 hours of immobility in the preceding
month
 Hospital admission in the past three months
 Surgery in the past three months
 Malignancy in the past three months
 Infection in the past three months
 Current hospitalization
Spenser FA et al.J Gen Intern Med. 2006;21(7):722
History of prior VTE
 Previous thrombotic episodes are a major risk factor
for recurrent VTE
 risk is highly dependent upon patient-specific
factors.
 idiopathic VTE or when active cancer is present have
higher rates of recurrence
 time-limited, reversible risk factors (eg, recent major
surgery, immobilization) low risk
DVT consider prior probability
Wells score or criteria: (Possible score −2 to 9)
 Active cancer : +1 point
 Calf swelling ≥ 3 cm compared to asymptomatic calf
(measured 10 cm below tibial tuberosity): +1 point
 Swollen unilateral superficial : +1 point
 Unilateral pitting edema : +1 point
 Previous documented DVT: +1 point
 Swelling of entire leg: +1 point
DVT consider prior probability
Well score continued
 Localized tenderness along the deep venous system: +1
point
 Paralysis, paresis, or recent cast immobilization of lower
extremities: +1 point
 Recently bedridden ≥ 3 days, or major surgery requiring
regional or general anesthetic in the past 12 weeks: +1
point
 Alternative diagnosis at least as likely: −2 points
 Score 0: <5%, low, D-dimer
 Score 1-2: 17%, moderate, D-dimer or US
 Score 3 or more: 53%, high, US
Antithrombotic Therapy for DVT
 Provoked
 Start with parenteral anticoagulant
 LMWH, Fondaparineux>UFH (weak rec)
 Distal DVT
 Serial imaging
 Treatment
 Start VKA on day 1
 For proximal DVT without PE 3 months
 Unprovoked
 Treat > 3 months
 Cancer LMWH>VKA
 No cancer VKA>LMWH
Case 2
 A 70 year old man presents for a second opinion
because of pulmonary hypertension.
 He had had a PE diagnosed 10 months ago and had
appropriate anticoagulation which he is currently
taking
 The PE was not related to a short-term reversible
factor
 The echocardiogram at the time of the embolism
showed a mildly dilated right ventricle, PA systolic
pressure 40 mmHg
Case 2
 He states that his
mother had had a PE
but she had cancer
 The repeat
echocardiogram is
now normal
 His protein C, S, AT
III levels were normal
Repeat Q
Case 2
Questions
 Does he have CTEPH (Chronic PE)?
 Should he have other testing for thrombophilia?
 Should he continue warfarin?
Thrombophilias
 Factor V Leiden mutation
 Prothrombin gene mutation




Protein S deficiency
Protein C deficiency
Antithrombin deficiency
Dysfibrinogenemia
Acquired Thrombophilia










Malignancy
Presence of a central venous catheter
Surgery, especially orthopedic Trauma
Pregnancy
Oral contraceptives, Hormone replacement therapy, Tamoxifen,
Thalidomide, Lenalidomide
Immobilization
Congestive heart failure
Antiphospholipid antibody syndrome
Myeloproliferative disorders, Polycythemia vera, Essential
thrombocythemia, Paroxysmal nocturnal hemoglobinuria
 Inflammatory bowel disease
 Nephrotic syndrome
Upper extremity DVT
 Axillary vein or more proximal: treat
 LMWH, Fondaparineux>UFH (weak rec)
 Start VKA on day 1
 Removal of catheter: not necessary
 Treat like a lower extremity DVT
 Treat > 3 months
 With catheter as long as catheter remains in place
Case 3
 A 60 year old woman presents with syncope. She has
metastatic colon cancer and a history of CHF. On
exam she is now awake and exhibits respiratory
distress on arrival to the ED so she is intubated. She
was recently admitted to the hospital with lower
gastrointestinal bleeding that required blood
transfusion.
 VS: BP 85/62, pulse 125, RR 26, SPO2 92% on 70%
oxygen
 A bedside echo demonstrates RV diameter=LV
diameter
 A CTA chest shows a “saddle PE”
Questions to consider
 What should be used as the initial therapy?
 Thrombolysis?
 Anticoagulation?
 Thrombectomy?
 Catheter directed thrombectomy?
PE consider prior probability
 The Wells score for PE
 clinically suspected DVT - 3.0 points
 alternative diagnosis is less likely than PE - 3.0 points
 tachycardia (heart rate > 100) - 1.5 points
 immobilization (>= 3d)/surgery in previous four weeks 1.5 points
 history of DVT or PE - 1.5 points
 Hemoptysis- 1.0 points
 malignancy - 1.0 points
Diagnosis of acute pulmonary embolism
 Clinical findings: not sensitive nor specific
 Sudden dyspnea, chest pain, hemoptysis, syncope
 Labs are not sensitive
 ABG, BNP, Troponin
 EKG is not sensitive
 Echo is not sensitive
 Radiographic findings while common are not specific
Diagnosis of acute pulmonary embolism
VQ scan
Prospective Investigation of Pulmonary Embolism
Diagnosis (PIOPED)
1. High clinical probability of PE and a high-probability
V/Q scan had a 95 percent likelihood of having PE
2. Low clinical probability of PE and a low-probability
V/Q scan had only a 4 percent likelihood of having
PE
3. A normal V/Q scan virtually excluded PE
Most patients do not fit into categories 1,2 or 3
Diagnosis of Acute PE
 Extremity US
 Many patients with PE are likely to be missed.
 Complete venous imaging may improve sensitivity
 Serial imaging is better than a single study
Turkstra F et al. Ann Intern Med. 1997;126(10):775
Diagnosis of Acute PE
 Angiography remains the “gold standard”
 A negative pulmonary angiogram excludes clinically
relevant PE
 CTA when combined with clinical assessment is the
best combination of practicality and accuracy
 positive CT-PA high, intermediate, or low clinical
probability was 96, 92, and 58 percent (PPV)
 If CTA results are discordant with clinical
impressions then further studies are warranted
Stein PD et al. Radiology 1999;210:689.
Stein PD et al. N Engl J Med. 2006;354(22):2317
PE: Massive, submassive, low-risk
Figure 1. Overall mortality (A) (log-rank
P<0.001) and cardiovascular mortality (B)
(log-rank P<0.001) in 108 patients with
massive PE and in 2284 patients with
non–massive PE.
Kucher N et al. Circulation
2006;113:577-582
Copyright © American Heart Association
Massive PE
Definition for massive PE:
 Acute PE with sustained hypotension (systolic blood
pressure < 90 mm Hg for at least 15 minutes or
requiring inotropic support, with signs or symptoms
of shock
 and shock is not due to a cause other than PE, such
as arrhythmia, hypovolemia, sepsis, or left ventricular
[LV] dysfunction), or persistent profound bradycardia
(heart rate 40 bpm
 Treat with thrombolysis in the absence of a
contraindication
 Consider alternative modalities
Low-risk PE
 Low-Risk PE
 Normotensive with normal biomarker levels and no
RV dysfunction on imaging with short-term mortality
rates approaching 1%.
 Do not use thrombolysis
Submassive PE
 “All the rest”
 Definition for submassive PE: Acute PE without
systemic hypotension (systolic blood pressure 90
mm Hg) but with either RV dysfunction or myocardial
necrosis.
Clinical Risk factors
 Cancer
 Congestive heart failure
 SBP<100 mmHg
 Hypoxemia
 Others
 Wicki et al. Thromb Haemost 2000;84:548-552.
 Aujesky et al. Am J Respir Crit Care Med. 2005;172:1041–1046.
Submassive PE
 RV dilation (apical 4-chamber RV diameter divided by
LV diameter 0.9) on CT or echo
 RV systolic dysfunction on echocardiography
 Elevation of BNP (90 pg/mL)
 Elevation of N-terminal pro-BNP (500 pg/mL); or
 Electrocardiographic changes (new complete or
incomplete RBBB, anteroseptal ST elevation or
depression, or anteroseptal T-wave inversion)
 Elevation of troponin I (0.4 ng/mL) or
 Elevation of troponin T (0.1 ng/mL)
Antithrombotic Therapy for PE
 Start with parenteral anticoagulant
 LMWH, Fondaparineux>UFH (weak rec)
 Distal DVT
 Serial imaging
 Treatment
 Start VKA on day 1
 For proximal DVT without PE 3 months
 Hypotension (SBP<90), low bleeding thrombolytics
are suggested
 Submassive PE, high risk without hypotension
consider lytics
 IVC filters
Thrombolysis
Jaff MR et al. Circulation 2011, 123:1788-1830
Case 4
 A 44 y/o man presents with progressive dyspnea
 6 weeks ago he injured his leg after which his leg
swelled
 He then experience hemoptysis that was self limited
 He underwent heart catheterization that showed no
CAD, normal LV function and moderately severe
pulmonary hypertension: mPAP 45 mmHg, PVR 12
wood units
Case 4
Q
V
Chronic Thromboembolic Pulmonary Hypertension
 The natural history of acute pulmonary embolism is
usually near-total resolution
 a minority of patients will develop (CTEPH)
 occurs in 0.57 to 3.8 percent of survivors of acute
pulmonary embolism but in over 10 percent of
those with recurrent PE.
 Leads to progressive pulmonary hypertension and
cor pulmonale
Pengo et al. N Engl J Med. 2004;350(22):2257
Lensing et al.Haematologica. 2010;95(6):970
CTEPH
 Treatment
 Parenteral anticoagulation
 VKA-lifelong
 Endarterectomy
 Treatment for pulmonary hypertension and cor
pulmonale
CTEPH: Diagnosis and selection for surgery
 Diagnosis
 Ventilation-Perfusion Scintigraphy
 CT angiography
 Pulmonary angiography
 Angioscopy
 Surgical candidates
 Pulmonary thromboendarterectomy is only able to
remove thromboemboli whose proximal location is
in the main, lobar, or segmental arteries
Main Points
 VTE is common and can be fatal so prevention of
recurrent VTE is a priority
 The duration of anticoagulant is dependent on the
factors associated with the VTE episode
 Screening for thrombophilia is generally not
indicated
 When PE occurs it should be categorized as massive,
submassive or low risk to help with treatment
decisions
 Some PEs persist and result in CTEPH.