VTE / PE

    Pathophysiology

    • Typically thrombus arises in deep leg venous system.  It lodges into the pulmonary circulation.
    • 10-30% embolize to become pulmonary embolism (PE).
    • Acute PE vs. Chronic PE and Large vs. Small
      • When clot lodges --> acute increase in pulmonary arterial and RV pressures, decrease in cardiac output.
        • Increased V/Q mismatch --> hypoxemia. 
    • 300,000 people die in US from acute PE each year.

    Risk Factors of VTE

    • DVT risk factors (Virchow’s triad)
      • 1.  Hypercoagulability
        • Hereditary:
          • (Protein C/S def, Factor V Leiden, Prothrombin gene mutation, Dysfibrinogenemia, Antithrombin III deficiency)
        • Acquired:
          • Malignancy (+ chemo)
          • OCP, HRT
          • Pregnancy
          • Hematologic (Polycythemia vera, APLA)
      • 2.  Endothelial Damage
        • Trauma
        • Smoking
        • Surgery
        • Vascular manipulation
      • 3.  Stasis
        • Surgery 
        • Long flight/plane ride (Increases risk by 18% for each 2hour increment)
        • Obesity
        • Age (>60yo doubles risk each decade)
        • Hospitalization / Acute illness
    • Another way to think about it: THROMBOSIS
      • T - Trauma, Travel
      • H - Hypercoagulable, hormone replacement
      • R- Recreational Drugs (IV use)
      • O (old age >60)
      • M - Malignancy
      • B - Birth Control Pill
      • O - Obesity, Obstetrics
      • S - Surgery/Smoking
      • I - Immobilization
      • S - Sickness (CHF/MI, nephrotic syndrome, IBD, vasculitis, etc...)

     

    Pulmonary Embolism (PE)

    Symptoms

    • Patients with PE have few symptoms, and many non-specific and non-sensitive.
    • General Symptoms:
      • Tachypnea (90%)
      • Chest or pleuritic pain (85%)
      • Dyspnea (84%)
      • Anxiety, crackles, cough.
      • Likelihood of PE is lower if does not have dyspnea or tachycardia.

     

    Pre-Test Probability 

    • Signs an symptoms are non-sensitive and non-specific
    • Several diagnostic Risk Scores have been developed to decrease need for imaging.

     

    • Here are some prediction scoring systems:
    Well's Criteria for PE
    • Clinically suspected DVT                        (3 Points)
    • Alternative dx is less likely                      (3 Points)
    • Tachycardia > 100                                  (1.5 points)
    • Immobilization/Surgery in past 4 weeks  (1.5 points)
    • Hx of prev DVT or PE                              (1.5 points)
    • Hemoptysis                                              (1.0 points)
    • Malignancy (tx within 6 mo, palliative)     (1.0 points)
    • Traditional Interpretation
    • Score >6.0 – High (probability 59%)
    • Score 2.0-6.0 – Moderate (29%)
    • Score <2.0 – Low (15%)  (consider D-dimer)
    • "Modified Scoring"
    • Score >4 – PE likely, consider dx imaging
    • Score =< 4 – PE unlikely, consider D-dimer

     

    • Revised Geneva Scoring System
    Revised Geneva Scoring System

    Risk Factors:

    • Age > 65y                                                    (1 point)
    • Prev DVT or PE                                           (3 points)
    • Surgery under GA or fracture of LL in 1mo  (2 points)
    • Active Cancer (if active or cured in <1yr)     (2 points)

    Symptoms

    • Unilateral Lower Limb Pain                          (3 points)
    • Hemoptysis                                                  (2 points)

    Clinical Signs

    • Heart Rate 75-94/min                                   (3 points)
    • Heart Rate ≥ 95/min                                     (5 points)
    • Pain on LL deep venous palpation               (4 points)
      and unilateral edema

    Pretest Probability of PE:

      0 - 3   points = LOW

      4 - 10 points = INTERMEDIATE

      ≥11 points    = HIGH

     

    • PERC rule: (Pulmonary Embolism Rule Out Criteria)
    • Used mostly used by ER physicians (for VERY LOW pre-test probability)
    • 1. Age <50

      2. HR <100

      3. O2 sat >94% on RA

      4. No Hx of DVT/PE

      5. No recent surgery

      6. No hemoptysis

      7. No estrogen replacement

      8. No clinical signs of DVT

      If all are negative: <2% chance of PE

      Can use only if DO NOT suspect PE

     

    • Use of D-Dimer in patients with suspected PE/DVT will save 30% of pts from further investigations.
      • D-Dimer not recommended for moderate to high risk of PE or in hospitalized patients.
      • Use only if LOW pre-test probability (if high risk of PE, D-dimer does not change pretest as much)

     

    Initial Investigations / D-Dimer

    • ECG, CXR to rule out other causes (Pneumonia, ACS)
      • ECG in PE:
        • Most common: sinus tachycardia.
        • R-sided heart strain: (most aren't large enough to cause R-heart strain)
          • S1Q3T3 (only seen in minority of patients)
          • R-axis devation and RBBB
          • Large R-atrium.
      • CXR: Hampton's Hump (wedge shape density in the periphery due to infarction) or Westermark sign (darker area of reduced perfusion)
    • HamptonsSign.pngWestermarkSign.png
      • Hampton's Hump                                                    Westermark's sign

     

    • D-Dimer:
      • Use of D-Dimer in patients with suspected PE/DVT will save 30% of pts from further investigations.
        • D-Dimer not recommended for moderate to high risk of PE or in hospitalized patients.
        • Use only if LOW pre-test probability (if high risk of PE, D-dimer does not change pretest as much)
      • Negative Predictive Value = 94%
        • D-Dimer is NOT useful when POSITIVE (poor specificity), only useful if negative.
        • In pregnant patients D-dimer levels increase, but still useful in first trimester as at least 50% will normally have a negative D-dimer, which safely excludes TE.
          • In 2nd trimester 75% will be positive, and in 3rd trimester nearly all are positive.  If positive may need a low-dose perfusion scan or V/Q scan, consult radiology.

     

    Definitive PE Studies

    • CT angio (Sn + Sp >90%)
      • Primary method of diagnosis of PE due to high Sn and Sp.
      • Advantages:
        • May provide other diagnostic clues.
        • Preferred if baseline CXR abnormal (VQ scan difficult to interpret)
      • Disadvantages:
        • High radiation exposure
        • More challenging in obese people (hard to time contrast to pulmonary vasculature).  May need an open scanner.
    • V/Q scan  (Sn 50-98%, Sp 20-60%)
      • VQ scan is an option if CT angiography not available or contraindicated.
      • Advantages:
        • Low radiation dose.
        • No contrast dye.
        • Useful with normal cardiopulmonary status at baseline.
        • Preferred for chronic PEs with multiple lobar perfusion defects w/o anatomic matching ventilation abnormalities.  
        • Normal results practically exclude PE in setting of high pretest probability.
      • Diasadvantages:
        • Unreliable if structural lung disease (COPD, etc..) or if holding breath is difficult.
        • VQ interpretation dependent on pre-test likelihood.
    • Gold Standard: Conventional pulmonary angiography with digital subtraction
      • Invasive: only reserved for patients if uncertainty remains after CT angiography.
      • OR if direct measurement of hemodynamics is needed.

     

    DVT Studies in PE

    • If unable to get chest imaging to exclude PE, it may be worthwhile to perform a compression ultrasound of legs.
      • 90% of clots start in legs.
      • If positive leg venous ultrasound --> will treat for DVT and presumed PE (treatment similar)
    • If no DVT is found: may need chest imaging.
    • If PE is found on chest imaging --> Leg USS is not indicated (will not change management)

     

    Other Investigations

    • Echocardiography
      • For select patients with suspected or confirmed PE who are too unstable for CTA or VQ scanning.
      • Findings:
        • Elevated PA systolic pressure.
        • RV dilation / hypokinesis
        • Paradoxical septal motion
        • Diminished LV size.
        • **McConnel Sign**

    Treatment:

    • Tx almost the same for DVT and PE.  No evidence that PE needs different LMWH or warfarin therapy.
      • Tx reduces PE mortality from 30% to 2-8%
    • For PE: Decide if hemodynamically stable or not.
    • Can use cardiac markers of strain to help distinguish if significant or not (Trop, BNP, echo), but not used for used in criteria for "unstable".

    Stable

    • Achieve anticoagulation within 24hrs to prevent progression and recurrence of clot.
      • Allow time for natural lysis of existing clot (days to weeks).
      • Acutely use: UFH, LMWH, and rarely Fondaparinux (pentasaccharide)
        • New oral medications (rivaroxaban, dabigatran etc..) possible but less experience.
      • If anticoagulation (active internal bleed, hemorrhagic stroke, coagulopathy, remote GI bleed, brain mets).  Must weigh risks--benefits. 
      • Can start warfarin right away, but do not bolus (initially hypercoagulable), and continue LMWH/UFH for 4-5 days until reach target INR levels and >2 days of stable INR. (2 days overlap) to ensure reliable anticoagulation.
    • Big controversy whether thrombolytics should be used for stable patients but RV strain on CT or Echo.
      • Dilation, decreased RV systolic function.
      • Can look at biomarkers (troponin, BNP levels)
      • Area of active research, no definitive answer.

     

    Unstable

    • These are patients that have high mortality rate, and may require thrombolysis.
    • They are hemodynamically unstable patients have high risk of death:
      • NO TIME to wait for natural clot resorption --> Thrombolytic therapy, followed by anticoagulation.
      • Other options:
        • Catheter embolectomy or surgical embolectomy.
    • Defined as refractory hypotension
      • Very high pulmonary vascular resistance and high pulmonary pressure.  Drop in cardiac output. 
      • May need mechanical ventilation.
      • Give VOLUME --> fluid rescucitation to improve preload to RV.
        • However too much fluid can overload the RV (can cause ischemia of RV).
    • Contraindications for thrombolytic therapy:
      • Contraindications to Thrombolytic Therapy

        Absolute

        • History of intracranial bleeding
        • CVA within the past 3mo (ischemic CVA within the past 3 hours)
        • Closed head or facial trauma within the past 3 mo
        • Suspected aortic dissection
        • Active internal bleeding
        • Uncontrolled hypertension (sBP > 180, dBP > 100)

        Relative

        • Current anticoagulation or bleeding diathesis
        • Surgery or invasive procedures in the past 2 weeks
        • Prolonged CPR ≥ 10min
        • Controlled severe HTN
        • Diabetic or hemorrhagic retinopathy
        • Pregnancy

         

        Risks of thrombolysis:

        - 2.1% risk of ICH

        - 1.6% risk of fatal non-ICH hemorrhage.

     

    Long-Term Management

    • In acute PE, pts are at a substantial risk of recurrence (esp in first 1 month)
    • Continue anticoagulation for at least 3 months.
    • Standard therapy:
      • Warfarin (INR 2-3)
      • NEW: Rivaroxaban
    • How long to continue?
      • 3 months of anticoagulation for everyone, after that:
        • Can stop if known predisposing factor that is resolved.
        • Continue as long as predisposing factor present (surgery, immobility)
        • Consider indefinitely if:
          • predisposing factor continuous (cancer).
          • History of proximal DVT
          • Idiopathic  (aka "unprovoked") VTE
      • Some perform D-Dimer 2 weeks before stopping anticoagulation and also check 2-weeks after stopping.
        • If positive, then four-fold risk of recurrent PE than normal D-Dimer.
        • Helps risk-stratify, if D-Dimer positive --> consider continuing.
    • NOTE: For patients requiring long-term oral anticoagulants, role of NOACs is uncertain.

     

    IVC Filters

    • Indications:
      • If not candidate for acute or chronic anticoagulation.
      • Clotting despite anticoagulation
      • High risk of recurrent emboli
      • Low cardiopulmonary reserve (such as pulmonary HTN) - even if on anticoagulation.
    • Placed into IVC below renal veins.
    • Prevent any DVTs that embolize.
    • Disadvantages:
      • Higher risk of lower-limb DVT with filter in-situ.
      • Filter can migrate (even into RV)
      • Filter can endothelialize if not removed after few months (will be impossible to safely remove)
      • Clot can form on filter, above filter, or around the filter. (Can cause chronic pain)
      • Can get venous collateralization around the filter, and emboli can bypass.
    • Preferrable to continue anticoagulation after filter installed.
    • MOST (80-90%) are never removed and forgotten.  DO NOT forget to remove if not needed.

     

     

    VTE Prophylaxis

    Based on CHEST Guidelines "Prevention of VTE in Nonsurgical Patients", Feb 2012.

    • Risk Factors:
      • NYHA class III/IV HF
      • Acute respiratory failure
      • Active cancer
      • Stroke with paresis
      • History of VTE
      • Acute infectious illness
      • Age >60 years
      • Thrombophilia
      • Acute rheumatic disease
      • Inflammatory bowel disease
      • Immobility
    • Divide patients into LOW and HIGH risk.
    • All acutely ill hospitalized medical patients at increased risk of thrombosis need thromboprophylaxis with:
      • Low Molecular Weight Heparin (LMWH)
        OR
      • Low Dose Unfractionated Heparin (LD UFH) BID or TID
        OR
      • Fondaparinux

     

    • VTE Risk Factors Prophylaxis Options Contraindications to VTE proph
      • NYHA class III/IV HF
      • Acute respiratory failure
      • Active cancer
      • Stroke with paresis
      • History of VTE
      • Acute infectious illness
      • Age >60 years
      • Thrombophilia
      • Acute rheumatic disease
      • Inflammatory bowel disease
      • Immobility

      Unfractionated Heparin, 5000u SC q8-12h

       

      Enoxaparin, 40mg SC q24h

       

      Dalteparin 5000u SC q24h

       

      Fondaparinux, 2.5 SC q24h

       

      OR

      Intermittent pneumatic compression (if

       pharmacologic contraindicated)

      - Active or high risk of bleed

       

      - Coagulopathy (abnormal PTT or

        PT not due to lupus anticoagulant)

       

      - Thrombocytopenia (<50,000/uL)

      In pts with stroke, active cancer, surgery --> LMWH is superior to UFH.

     

    Superficial Thrombophlebitis

    • Superficial vein thrombosis.
    • Same as DVT: Use therapeutic dose of LMWH / Heparin.
      • In the past superficial vein thrombophlebitis used with ibuprophen and compression stalkings.
      • However, recent studies has similar risk factors as DVT.  It can progress to cause true DVT and PE.
    • Vein ligation used for symptomatic recurrent thrombophlebitis.

     

    CTEPH

    • Chronic Thromboembolic Pulmonary Hypertension
    • Lifelong anticoagulation with warfarin
    • No trials comparing shorter anticoagulation, or anticoag vs. surgery.
    • Assess all patients for surgery
      • Pulmonary Thromboendarterectomy Assessment
        • Surgical Accessibility (main, lobar, segmental)
        • Hemodynamic/ventilatory impairment
        • Comorbidities/Risks of Surgery
        • Patient preference

    Guideline Update 2016 Chest

    Click: Download PDF Chest 2016 Guideline

     

    • DOACs = Dabigatran, Rivaroxaban, Apixaban, Edoxaban
    • Choice of Anticoagulation Agent:
      • No Malignancy
        • 1st line: DOAC
        • 2nd line: VKA
        • 3rd line: LMWH
      • Malignancy
        • 1st line: LMWH  (CLOT Trial = LMWH vs. Warfarin in malignancy)
        • 2nd line: Warfarin
    • Anticoagulate?
      • Distal Leg DVT:
        • RF for Progression OR Significant Symptoms?
          • YES --> Treat x3mo (Same agents)
          • NO --> Serial imaging of deep veins x2w
      • Subsegmental PE (and no proximal leg DVT)
        • Low Risk of Recurrent VTE --> Surveillance
        • High Risk of Recurrent VTE --> Anticoagulate
      • Indications for Thrombolysis of PE
        • sBP < 90mmHg (despite resuscitation) + Low Risk of Bleeding
        • Cardiopulmonary Deterioration despite anticoagulation (if not yet hypotensive) + Low Bleeding Risk
          • Includes: Symptoms, vitals, tissue perfusion, gas exchange, cardiac biomarkers
      • CTEPH (chronic thromboembolic pulmonary hypertension)
        • Consider pulmonary thromboendarterectomy (consult experienced team)
        •  
      • Upper Extremity DVT (Axillary or more proximal veins)
        • Anticoagulate!
        • Thrombolysis can be considered in select pts (see guideline), but must still anticoagulate
      • Recurrent VTE
        • Switch to LMWH for at least 1mo AND Re-evaluate (evaluate compliance + malignancy)
        • If have recurrent VTE on LMWH (compliant) --> increase dose of LMWH (1/4 to 1/3) 
    • Duration of Therapy
      • Duration of Therapy 4.png

    • NOTES:
      • Catheter directed thrombolysis NOT RECOMMENDED (peripheral vein systemic therapy preferred)
      • Catheter thrombus removal if:
        • High bleeding risk
        • Failed systemic thrombolysis
        • Shock that is likely to cause death before systemic thrombolysis can take effect (hrs)
      • Edoxaban and Dabigatran need initial IV anticoagulation (rivaroxaban and apixaban do not)
      • Do not use compressions stockings to prevent post-thrombotic syndrome.

    Indications for Thrombophilia Testing

    Indications for thrombophilia workup

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