L21 - When to Suspect and How to Diagnose and Treat PE Flashcards
Which is FALSE regarding pulmonary embolisms?
A. Venous thromboembolism (VTE) Spectrum: includes DVT & PE
• DVT = thrombus in vein
• Embolism = piece that has lodged off and goes to the lung
B. PE = Rare but deadly diseases that few people outside of medicine think much about
C. Only 30% patients w/ PE diagnosed prior to death (autopsy study 1982)
D. 300,000 to 900,000 cases/year in the U.S.
E. Approximately 50,000 deaths/year in the United States
B. VERY common
DVT = thrombus in vein Embolism = piece that has lodged off and goes to
Which is true regarding the pathophysiology of pulmonary embolisms?
A. Most emboli arise from a thrombus within distal ileofemoral veins
B. Ileo-femoral thrombi grow/extend symptomatically & embolize recurrently when not treated
C. Localized embolic obstruction results in release of vasoactive compounds causing dilation throughout pulmonary vascular bed.
D. Large emboli lodge in main pulmonary arterial tree, block large portions & produce acute R heart failure/Death
E. Distal small emboli may occur frequently w/ major consequences
F. When you are treating an embolism, you are trying to break down the embolism
D
A. proximal
B. asymptomatically
C. constriction throughout
E. minimal consequences due to powerful endogenous thrombolysis
F. you are actually preventing the next one (without treatment you will likely have a embolism shortly after) - endogenous thrombolytic system will remove the current embolism
T/F Prevention is preferable to cure in the modern version of the Hippocratic oath
True - Prevention must be considered in every hospitalized patient
General prophylactic therapy recommendations in:
- medical, low bleeding risk patients is ____?
- High risk bleeding patients and VTE is ____?
- unfractionated heparin, LMWH
2. pneumatic stockigns
What is not a challenge/conundrum of pulmonary embolisms?
A. Considering PE as a diagnostic possibility
B. Ordering the appropriate tests
C. Institute timely and effective Rx (balance against the risk of bleeding)
D. Most PE arise from proximal deep veins of LE, BUT…
• May come from UE, renal/pelvic veins, R heart or
• Popliteal/calf vein thrombi unlikely PE source, BUT ~20% propagate distally (can then form PE)
E. Early treatment prevents recurrence (eg, sudden death), BUT… tx associated with risk (eg, bleeding, 5% HIT - heparin induced thrombocytopenia - autoimmune reaction)
D. proximally
Which is not one of the 5 most common RF for PE A. Oral contraceptives B. Immobilization C. Surgery w/in prior 3 months D. Stroke E. H/O VTE
A. Malignancy is more of a RF
• Others: less common but still important
• Obesity
• Smoking
• Oral contraceptive Rx
• Pregnancy
• Lupus anticoagulant & Anti-phospholipid Ab
• hereditary…(e.g. heretditary thrombophilia)
2 main examples of hereditary thrombophilia which result in hypercoagulable states
- factor V Leiden mutation (3-7% prevalence in the general population)
- Prothrombin gene mutation (1-3% prevalence in the general population)
• Uncommon (
- The onset of PE is (acute/chronic)
- HPI: Dyspnea, apprehension, chest pain (pleuritic), hemoptysis. Which is most common?
- Exam: pleural rub, wheezing, loud P2, tachypnea, tachycardia, leg swelling. Which are most commonly seen?
- acute
- dyspnea
- tachypnea and tachycardia
T/F Clinical findings are reliable for diagnosis of PE?
FALSE
- What clinical test for PE is considered the gold standard
2. When should you consider this test?
- pulmonary angiogram - invasive, expensive, but safe
- Consider pulm angio when noninvasive tests are negative or indeterminant, and there is no plausible competing diagnosis
T/F Most chest x-rays can yield specific findings of PE like Hampton’s Hump
False - Hampton’s Hump (pleural based wedge shaped density) is pathognomonic for PE…
… BUT MOST CXR YIELD NON-SPECIFIC FINDINGS
T/F ECG findings such as acute right heart strain patterns are generally sufficiently sensitive and specific to rely upon
False - acute right heart strain pattern (S1Q3T3) in otherwise healthy individual that comes in with SOB and chest pain
• Indicates large PE - rare
• But…ECG findings are generally insufficiently sensitive & specific to rely upon
Which is FALSE regarding diagnosis of PE?
A. 80% PE dx prior to death (1982)
B. 6-40% suspected PE, actually have it (current ~6%)
C. Key Hx (PE Risk Factors): Recent trauma, surgery, immobilization, Malignancy, prior VTE or FHx
D. Limited value of Physical exam…tachypnea, tachycardia, loud P2
E. DDx is extensive (clinical conundrum)
F. Pre-test Probability assessment (useful if it’s been caudified) e.g. Wells criteria
G. Diagnostic tools like V/Q scan,D-dimer, Lower extremity ultrasound, CT angiography, and Conventional pulmonary angiography used after pre-test probability assessment
A. 30%
Fill in the blanks for Wells Criteria:
- Clinical symptoms for DVT = ________ points
- Another diagnosis (more/less) likely than PE = 3 points
- HR greater than ____ = 1.5 points
- Immobilization (more than 3 days)/surgery w/in 4 weeks = _______ points
- Previous ___ or ____ = 1.5 points
- Hemoptysis = ______ points
- malignancy = _____ points
- 3
- less
- 100
- 1.5
- DVT or PE
- 1
- 1
A wells score:
- greater than ______ is high probability
- ______ is moderate probability
- less than ______ is low probability
- Greater than _________ is likely
- Less than or equal to ____ is unlikely
- 6
- 2-6
- 2
- 4
- 4
V/Q scan
Coupled w/pretest assessment:
1. Normal/low prob scan rules (in/out) PE
2. High prob scan rules (in/out) PE
- Out
- In
Today V/Qhas been supplanted by CT angio since majority of patients have intermed prob and 40% have PE
- What does a high D-dimer indicate?
2. D-dimers form when (fibrin/fibrinogen) is converted to (fibrin/fibrinogen)
- High amount of d-dimers mean more clots are present and suggest PE.
- D-dimers form when fibrinogen is converted to fibrin
What is false regarding quantitative D-dimer test?
A. Quantitative ELISA (or advanced turbidimetric) provides high sensitivity (~95%)
B. Standard positive threshold > 500 (suggests clotting)
C. Negative ELISA ≅ negative predictive value of V/Q or LE Doppler U/S
D. Unidirectional… (most helpful when negative)
• Negative: rules in VTE, especially when coupled w/ low or intermediate pretest probability (eg, Wells)
• Positive: sufficient specificity to ↑ certainty of VTE
D. Unidirectional… (most helpful when negative)
• Negative: rules out VTE, especially when coupled w/ low or intermediate pretest probability (eg, Wells)
• Positive: insufficient specificity to ↑ certainty of VTE
Why do false positives occur frequently in D-dimers? (3)
- Surgery in the last 3 months
- Malignancy, pregnancy
- Age greater than 50 yo bc the cut point increases from 500 to be positive (adjust positive threshold to agex10)
e. g. 79 yo person would have positive threshold of 790 rather than 500
T/F Diagnosis of DVT Trumps PE Work -up
T
• If you find DVT (usually by ultrasound) you can treat & stop looking for PE
• Treatment of DVT & PE are virtually identical
LE doppler ultrasound is a Color flow US w/ compression prox. deep veins
Which has a higher sensitivity?
A. Patient with 1st episode, outpatient setting
B. Hospitalized setting, asymptomatic
A. Sens/Spec 89-100%
B has a lower sensitivity
~30-40% of PE + patients have negative LE Doppler U/S
What if LE Doppler U/S negative and can’t do CT angio?
do serial LE studies
What test is this?
- New generation CTs: Multidetector-row 16 ⇒64… (acquires data fast and with better resolution)
- Entire chest, 1 breath hold,
Multi-Detector Chest CT Angiogram
3. - have found Pes here but don’t know if sig bc wasn’t able to see this resolution bf
Christopher Study
Simplified algorithm evaluation of PE and created a validated paradigm that incorporates chest CT angiogram with Wells.
What is the algorithm?
Wells clinical decision rule greater than 4 or positive D-dimer then do chest CT angiogram
• Excluded PE acutely AND followed up long enough (3 months) to show very few subsequent nonfatal/fatal venous thromboembolic event
What do you do if Wells score is less than or equal to 4 (aka PE unlikely?)
Check D-dimer
• Low D-dimer = PE excluded
• High D-dimer = Further w/u
What do you do if Wells score is greater than 4 (aka PE likely?)
Further diagnostic testing, primarily CT angiogram
But can also do duplex doppler fo LE, V/Q scan, pulmonary angiography or MR angiography and venography
when suspicion high for PE & awaiting confirmatory data what treatment should you start?
immediate anticoagulation
- Upon firm diagnosis of PE what treatment should be done?
- In what situation would you stop treatment at 3 months?
- In what situation would you extend treatment to 6 months?
- Anticoagulation for 3 months
- first episode PROVOKED by temporary RF like surgery
- first episode UNPROVOKED
- What’s a test to do to determine if you should continue anticoag treatment of PE?
- What’s the exception to this?
- D-dimer 1 month post completion. resume if positive
2. Recurrent PE (2 or more): 1 year anticoag→ Indefinite
What is this drug?
• Binds to & inactivates Factor Xa
• Better efficacy compared to unfractionated heparin (multiple trials, N ≅ 8500):
• Decreased recurrent thrombosis
• Decreased mortality
• Reliable pharmacokinetics permits daily/bid dosing
• No lab monitoring required
• Risk for heparin-associated thrombocytopenia (HIT) slightly less than unfractionated heparin
• Accumulates in patients with CrCl
Low molecular weight heparin
- Both anti -thrombin & anti -Xa activity
- Alternative to LMWH for acute PE Rx
- Major error is INADEQUATE early anticoagulation
- Weight based algorithm
- Monitor APTT; aim for 1.5 to 2 times control value
- Risk of recurrent PE & thrombocytopenia higher than LMWH
Unfractionated Heparin (UFH)
Which is false regarding Unfractionated Heparin (UFH)
A. Both anti -thrombin & anti -Xa activity
B. Alternative to LMWH for acute PE Rx
C. Major error is INADEQUATE early anticoagulation
• Weight based algorithm
D. Monitor APTT; aim for 1.5 to 2 times control value
E. Risk of recurrent PE & thrombocytopenia lower than LMWH
E higher
What condition results from the following?
• ~5% receiving Heparinè Venous & arterial clots
• Direct thrombin inhibitors (Lentz, April 2015)
• Argatroban, Lepirudin, Bivalirudin
• Administered continuous IV infusion
• Monitor APTT
• Short half-life (1-2h)
• Renal metabolized: Lepirudin & Bivalirudin
• Hepatic metabolized: Argatroban
• New oral Direct thrombin inhibitor: Dabigatran
Heparin Induced Thrombocytopenia (HIT)…
What is this anticoagulant?
• Warfarin used mostly, which inhibits γ-carboxylation of vitamin K dependent clotting factors (II, VII, IX, X)
• Long term oral anticoagulation
• May cause transient hypercoagulable state (inhibits protein C & S more rapidly than II, VII, IX, X)
• Not effective for at least 3 days
• Start after heparin started (as early as day 1)
• Must overlap heparin therapy for at least 5 days
• Monitor INR
• Titrate dose to achieve INR 2.0 to 3.0
• Labor intensive (multiple drug/food interactions)
Vitamin K antagonists
Standard Treatment for PE (non-massive)
Acute period (0-10 days) or long term (post acute to 3-6mo)?
• Goal: prevent thrombus propagation & recurrence
• LMWH, or unfractionated heparin
○ Continue at least 5 days
○ LMWH cost-effective è Early pt d/c or outpatient initiated
○ LMWH once daily equivalent efficacy to BID
• If HIT, use parenteral direct thrombin inhibitors
Acute period (0-10 days)
Standard Treatment for PE (non-massive)
Acute period (0-10 days) or long term (post acute to 3-6mo)?
• VKA (eg, Warfarin) from day 1 (Goal: INR 2.0-3.0)
• Cancer – LMWH in place of Warfarin long-term (Cancer ↑Risk for recurrence on warfarin)
long term (post acute to 3-6mo)
What drug/therapy is this?
• Direct Xa inhibitor: rivaroxaban, apixaban & edoxaban
• Direct Thrombin inhibitor: dabagatran
• All aiming to replace VKA
• LMWH/VKA paradigm will likely evolve d/t:
• All TSOA achieved non-inferiority to VKA for long-term Rx
• Good data supporting rivaroxaban as monotherapy (acute & long-term)
• Recent pooled meta-analysis: LMWH/(rivaroxaban or apixaban) showed trend in ↓ bleeding risk cp LMWH/VKA
• Negatives: No acute reversal agents, variable renal clearance, & expensive
Target Specific Oral Anticoagulants (TSOA)
When do you use thrombolytic therapy?
For patients with massive PE that are hemodynamically unstable when SP
What kind of therapy is described below?
• Tissue plasminogen activator (tPA) directly lyses embolus & leads quickly to hemodynamic stability
• 1 – 4% risk of intracranial bleed/death
• Less certain indication: Hemodynamically stable, but RV strain present. Benefits theoretically appealing, although not well supported by data
• Alternative: invasive extraction when anticoagulation or thrombolysis fails or CI
Thrombolytic therapy
- Indications for IVC Filters
1. Can’t tolerate anticoagulation • CNS or GI bleed • Frequent falls 2. Failed anticoagulation • Recurrent VTE despite adequate anticoagulation 3. Will likely die if recurrent PE • Chronic PE, Massive PE 4. Permanent vs. removable filters
