inpatient / pulmonology and critical care

Pulmonary Embolism and VTE

PDF coming soon!

If You Remember Nothing Else

Pulmonary emboli most commonly origjnate in the proximal veins in the legs/pelvis. Patients can present in cardiac arrest, or without symptoms depending on the severity. It should be on the differential and considered a "can't miss" in any patient who presents with dyspnea. D-Dimers are sensitive, thus useful for ruling out a PE when used in concert with other clinical findings and lab values. Anticoagulation does not break up the clot, but does prevent further cascading. The body's natural thrombolytic pathways will dissolve the clot over time.

Terminology for risk stratification for PE  has changed, but in general, high risk (formerly massive) involves compromising hemodynamics, and the treatment pathway involves more aggressively removing or busting the clot to prevent obstructive shock, hypoxemia, and cardiac arrest.

In patients with massive PE, respect the RV - do not overload the patient with fluids even if they are hypotensive, and avoid intubation if possible since patients will often collapse and code. If patients are crashing, give epinephrine, consider pulmonary vasodilators (either NO or epoprostenol), and get the PERT team involved immediately for consideration of thrombolytics or thrombectomy. Patients with massive PE can be great VA ECMO candidates since they have a largely reversible process as the cause of their deterioration.
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Clinical Pearls

• Well's Criteria for DVT and for PE are different - if low for PE or mod for DVT, get dimer or do the PERC score; if high for DVT or mod for PE get imaging
• No one physical exam finding is great for DVT dx, but together can create a clinical picture - (JAMA, 1998)
• EKG - normal EKG is seen in 20% of PE cases; tachycardia is most common at 28%, TWI V1-V4 seen in 7-14% (LR 1.8-3.7); S1Q3T3 (McGinn-White Sign) is rare at about ~8%; new RBBB is possible; also watch for STEs in aVR (Eur Respir J, 2005)
• Echo signs of RV overload/strain are enlarged RV, mod/severe TR, McConnell's Sign (RV apex contracting but free wall is not)
• CTPE signs of RV overload/strain are RV/LV diameter > 0.9
• troponin and lactate are overall good markers for telling you the risk of death in patients, even if its not specific to PE; BNP is also not a specific market for PE since it also measured LV stretch and can be high in both those with heart failure and CKD/ESRD
• Proximal DVT (iliac, femoral, popliteal) increased the risk for PE; if distal (below the knee), less concern
• A negative US Doppler study does not rule out PE (clots can migrate)
• D-Dimer <500 and med pre-test probability OR D-Dimer <1000 and low PTP, rules out DVT/PE (NEJM, 2019)
• Age-adjusted D-Dimer cut-off is age x 10 ((JAMA, 2014)); D-Dimer has high sensitivity and NPV but poor specificity
• DDx for elevated D-Dimer - arterial (MI, stroke, acute limb ischemia), DIC, cancer, infection, ESLD, renal disease, increased age, trauma, surgery
• Evidence of right heart strain - enlarged RV, flattened septum, TR, RV free wall akinesis
• May Thurner syndrome - anatomic variant - the L common iliac vein is compressed by R iliac artery, can cause DVT due to poor flow/stasis
• Heparin does not break up clot, it prevents further clot from forming while the body breaks down clot on its own
• Unprovoked DVTs have 10% recurrence rate within 1 year of being off AC, 5% per year thereafter
• Considered a “recurrent DVT” if happens after 2 weeks of being on AC therapy 
• If UE DVT, can leave in PICC/CVC if functional and no concern for infection, just continue AC while it is in
• If unprovoked, on discharge ensure age-appropriate cancer screening; hypercoagulability workup should not be done at the time of the acute VTE or on AC - one exception is if high concern for APLS (young woman, previous lost pregnancies, arterial clotting)
• In PE, PPV decreases venous return, decreased RV output, increases RV failure - if you can avoid intubating these patients and and instea keep them on HFNC, you might save their life - patients with massive PE who get intubated can have hemodynamic collapse and code - if you have to, consider pulmonary vasodilators, have epinephrine ready at bedside, try to use sedatives that will not lead to hypotension (ketamine),
• LMWH has faster therapeutic onset and longer duration of action than UFH, and you don’t have to check PTT
• Absolute contraindications for empiric AC is recent surgery, h/o hemorrhagic stroke, ischemic stroke in last 3 months, active bleeding
• You don’t have to give AC for subsegmental PE with low risk of recurrence
• DOACs may not be as reliable in patients with GI issues, malabsorption, or BMI >40
• Warfarin is titrated to INR 2-3
• Massive PE is a common cause of PEA arrest
• Massive PE leads to increased RV afterload, reducing CO, leading to obstructive shock - SVR will increase in response to the reduced CO and shock; PCWP will be lower; RV pressure will push septum against the LV leading to less LV diastolic filling, further dropping CO
• Vignettes will often have hemoptysis, JVD and Kussmaul sign, but all rare in real life
• Hampton Hump - wedge-shaped opacity on CXR - infarction, not specific for PE
• “Wedge-shaped infarction” on CT is essentially pathognomonic for PE, but is rarely seen
• Vignettes will often have hemoptysis, JVD and Kussmaul sign, but all rare in real life
• Virchow's Triad - venous stasis, vascular injury, hypercoagulability

Trials and Literature

• Risk Factors for PE - OR >10 (fracture, major surgery); OR 2-9 (OCP, hospitalized/SNF, previous VTE, malignancy, sepsis); OR <2 (bed rest, long travel, increased age, obesity, smoking, cirrhosis, CKD) (Circulation 2003)
• PE Prevalence in Syncope - Among patient’s hospitalized for the first episode of syncope is 1 in 6 - (NEJM, 2016) ; Among patients who just present to the ED, more like 1% (J Am Coll Cardiol, 2019) (note these patients were not the first episode of syncope); and for those who ended up getting admitted it was more like 2-3%
• PEITHO Trial - tPA in intermediate-risk PE showed no long-term benefit or change in mortality but led to increased major bleeding and hemorrhagic CVA - solidified the general idea is that we give tPA in massive PE to prevent immediate death, not to help with long-term outcomes (NEJM 2014)
• Thrombolysis for those with RV strain does improve mortality, but also increased severe bleeding episodes (JAMA 2014)
• Vena Caval Filters in PE ppx - Prevents the short-term occurrence of PE, but increased risk of recurrent DVT; After IVC filter placement can use either LMWH or UFH (NEJM 1998)
• tPA in intermediate-risk PE no long-term benefit or change in mortality but led to increased major bleeding and hemorrhagic CVA (NEJM 2014)
• There is currently no randomized data showing that catheter-directed tPA is superior to peripherally administered tPA at the same dose - but there is an ongoing trial attempting to answer this question
• FLARE Trial - thrombectomy (FlowTriever) to remove clot had great data in a single-arm study in patients with submassive PE - reduced RV/LV ratio and need for thrombolytic (JACC Cardiovasc Interv, 2019)
• iNOPE Trial - inhaled NO vs placebo in submassive PE - increased likelihood of having normal-sized RV, and is well tolerated (Am Heart J, 2017)
• The SOME Trial - Screening for Occult Malignancy in Unprovoked VTE - First unprovoked VTE - normal age-appropriate cancer screening vs. the addition of CTAP to look foro cancer; No sig differences in the number of occult malignancies diagnosed with CTAP; the most commonly missed cancers were lymphomas, gynecologic, colorectal (NEJM 2015) ; A Meta-Analysis on the topic - occult cancer detected in 1 of 20 patients within 1 year of receiving a diagnosis of unprovoked VTE; extra screening does not clearly improve outcomes
• The CLOT Trial - LMWH is better than Warfarin at preventing recurrent DVT in Patients with Malignancy (NEJM 2003)
• RE-COVER Trial  - DOAC (Dabigatran/Pradaxa) non-inferior to warfarin for treatment of VTE at 7 days and 6 months follow up (NEJM 2009)
• AMPLIFY Trial - Apixaban in VTE - Apixaban non-inferior to lovenox followed by warfarin in the treatment of VTESignificantly less major bleeding with apixaban vs. conventional therapy (NEJM 2013)
• EINSTEIN-PE Trial - Rivaroxaban to treat PE - Oral factor Xa inhibitor non-inferior in preventing recurrent VTE after PERate of major bleeding is significantly lower with rivaroxaban (NEJM 2012)
• SELECT-D Trial - Rivaroxaban low VTE recurrence but high clinically relevant bleeds v.s. dalteparin (JCO 2018)
• PREPIC-2 Trial - IVC filters + AC vs just AC in patients with submassive IVC had a trend towards harm (JAMA, 2015)

Other Resources

• Internet Book of Critical Care - Submassive and Massive PE
• PE Risk stratification algorithm from IBCC/EMCrit - link
• Example of thoughtful lytic dosing based on risk-stratification from IBCC/EMCrit - link
• MD Calc - PESI Score - risk of 30-day mortality and complications in patients diagnosed with PE; may not be terribly useful in the immediate setting when trying to risk stratify and make decisions on admission
• MD Calc - PERC Score - rules out PE if all criteria are negative and patient low-risk
• MD Calc - Well’s DVT - outpatient and ED - if low risk and neg D-Dimer, no need for US
• MD Calc - Well’s PE - inpatient and ED - likely vs unlikely for D-dimer vs. CTPE
• Curbsiders Podcast - DVT/PE Triple Distilled, PE for the Internist, DVT/PE Masterclass
• Core EM - CORE EM PE