Pulmonary Embolism

  • closure or narrowing of the pulmonary artery or its branches by embolic material - usually a thrombus
  • Sporadically:
    amniotic fluid, fat tissue after long bone fracture, tumour mass
  • clinical manifestations of venous thromboembolism (VTE):
    pulmonary embolism (PE) and deep vein thrombosis (DVT)

Proximal (from popliteal fossa and above) deep vein thrombosis is a common source of embolic material or rarely in the right heart (<10% of cases)

  • Epidemiology:
    30-day mortality – 6% DVT; 12% – PE
    If anticoagulant therapy is stopped in patients with VTE, the risk of recurrence is about 10% at 1 year and 30% at 5 years
    Chronic thromboembolic pulmonary hypertension (CTEPH) occurs in 2-4% of patients with PE (complication)

Symptoms

Dyspnoea > Chest pain ( commonly Pleuritic) > Symptomatic DVT (leg swelling, pain) > Cough > Hemoptysis, Syncope , Unilateral leg pain, Fever (> 38.5), jugular venous pressure (JVP) is raised

Pathophysiology

  • ↑ RV afterload --> RV dilation --> TV insufficiency --> ↑ RV wall tension --> neurohormonal activation --> Myocardial inflammation --> ↑ RV O2 demand --> RV ischemia --> ↓ RV contractility --> ↓ RV output --> ↓ LV pre-load --> ↓ CO --> ↓ systemic BP --> RV coronary perfusion --> ↓ RV O2 delivery --> cariogenic shock ---> Death

Diagnostic tests

  • Anamnesis, physical examination, gas analysis
  • ECG
    sinus tachycardia
    supraventricular arrhytmias (atrial fiblillation, atrial flutter)
    RV overload:
    incomplete / complete RBBB, QR pattern in V1
    negative T-wave in V1-V4, S-wave>0.15mV in I and aVL
  • Chest X-ray:
    Heart enlargement, Pleuritis, Elevated diaphragm, Atelectasis, Pulmonary oedema, Diminished vascular outline (Westermark sign), Pulmonary infarction (Hampton hump), pleural effusion
    , prominent central pulmonary artery
    In 30% of cases chest X-ray is normal
  • D-dimer testing:
    +Elevated plasma D-dimer levels:
    venous thromboembolism (DVT, PE)
    inflammation, infection, sepsis
    after trauma, operation, cancer
    acute coronary syndrome, DIC
    pregnancy, increase with with age
    +D-dimer level increases with age
    < 50 years of age: upper level < 500 μg/l
    ≥ 50 years of age: upper level < age x 10 μg/l
    +if this is undetectable, it excludes a diagnosis of pulmonary embolism.
    +most sensitive test for thromboembolic disease.
  • Compression venous USG:
    sensitivity 90%, specificity 95% for proximal DVT
    Reveals DVT in 30-50% of PE patients
    Proximal DVT in a patient with suspected PE is enough to apply anticoagulation without further examinations
  • Perfusion Scintigraphy
    Scintygraphy result could be :
     normal (excludes PE)
     high probability of PE
     non-diagnostic (30-50%)
    Scintigraphy is an examination of high sensitivity and low specificty
  • Computed tomographic pulmonary angiography (CT): „gold standard”
    Enables visualization of the pulmonary arteries down to at least segmental level (or sub-segmental when multi-detector CT)
    PE confirmation – when PE within at least segmental arteries (or larger arteries)
  • Pulmonary angiography:
    Previously the „gold standard” of diagnosis, nowadays totally replaced by CT
    Always should be preceeded by echocardiography (to exclude right heart thrombi)
    Indispensable when surgical embolectomy is planned
  • Echocardiography:
     right ventricular dysfunction
     RV enlargement
     RV diameter / LV diameter > 0.9-1.0
     ↑ maximal velocity of tricuspid insufficiency
    inter ventricular septal bulging into the LV
    dilated proximal pulmonary arteries

Diagnostic Algorythm

Clinical assessment and initial risk stratification

Screenshot 2018-10-12 at 15.43.59

Screenshot 2018-10-12 at 15.44.28

TREATMENT

  • Give oxygen and start heparin immediately before the diagnosis is confirmed and
    while the diagnostic workup is being completed.
  • Anticoagulation
    • unfractionated heparin (UFH)
    • low molecular weight heparin (LMWH)
    • fondaparynux
    • rivaroxaban (Xarelto), apixaban (Eliquis), dabigatran (Pradaxa)
    • warfarin, acenocoumarol
  • Thrombolysis (streptokinase, urokinase, rt-PA)
  • Embolectomy
    • surgical
    • percutanous (catheter directed)
  • Venous filters
    in patients with absolute anticoagulant contraindications
    in patient with recurrent VTE despite adequate anticoagulant treatment
    indicated after surgical embolectomy
  • When PE is probable, but without shock or hypotension
    Direct anticoagulation:
    First 5-10 days: use LWMH, UFH or fondaparynux
    Within the first 5-10 days add VKA: warfarin or acenocoumarol
    Stop LWMH, UFH or fondaparynux treatment when INR > 2.0 in 2 consecutive days
    Anticoagulation – for at least 3 months (often longer)

TREATEMENT of VTE

  • newer oral anticoagulants (NOAC) are preferred to VKA (warfarin) in acute and chronic treatment of PE and DVT (similar efficacy to VKA, but significantly less risk of bleeding)
    Rivaroxaban (Xarelto)
    Apixaban (Eliquis)
    Dabigatran (Pradaxa)

Screenshot 2018-10-12 at 15.52.55

Secondary prevention of VTE

50% of patients with proximal DVT have PE (asymptomatic)
70% of patients with PE have DVT of the lower extremities

VTE predisposing factors

  • Patient-related (constant): old age, previous VTE, cancer, Thrombophilia, neurological disease with peripheral paralysis, oral contraceptives
  • Situation-related (transient): surgery, trauma, pregnancy, APL Ab syndrome
  • inherited: Factor V leiden, Prothrombin gene mutation, Low protein C, protein S, antithrombin III
  • 30-50% of patients have no risk factors (idiopathic PE or DVT)
  • First VTE episode in the presence of transient risk factors (trauma, surgery, pregnancy, immobilization) --> Anticoagulation for 3 months
  • First VTE episode in the presence of malignant cancer --> LMWH: indefinitely or until cancer cure
  • First episode of idiopathic VTE --> Anticoagulation chronically/ indefinitely
  • Aspirin 100 mg daily for extended treatment of VTE in patients with un unprovoked proximal DVT or PE who are stopping anticoagulant therapy

Chronic anticoagulation: with NOAC, VKA or LMWH - if cancer
Anticoagulation decreases the risk of VTE recurrences by 80%, Aspirin – by 30%

criteria to diagnose PE

In Europe

Screenshot 2018-10-12 at 16.29.13

In US

Wells’ Criteria

• Symptoms of DVT (3 points)
• No alternative illness that explains symptoms (3 points)
• Immobilization (≥3 days) or surgery in the previous 4 weeks (1.5 points)
• Prior history of DVT or PE (1.5 points)
• Presence of hemoptysis (1 point)
• Presence of malignancy (1 point)

• Score <2 = low probability of PE • Score ≥2 but <6 = mean moderate probability of PE • Score >6 = high probability of PE

  • more than 50% of the pulmonary circulation is obstructed, the clinical signs become dominated

cardiac troponin

  • limited role in decision making
  • released due to right ventricular muscle damage in acute right heart strain in massive (>70% of one lung is involved) PE
  • High-risk:
    thrombolysis (urokinase, streptokinase, alteptase)
    embolectomy (contraindications to thrombolytic)
    anticoagulant (unfractionated heparin (UFH), LMWH, Fondaparinux – selective factor Xa inhibitor)

Virchow triad

  • alterations in blood flow,
    immobilization (after surgery), injury, pregnancy (also procoagulant), obesity (also procoagulant), Cancer (also procoagulant)
  • factors in the vessel wall
    surgery (knee replacement carries a 70% risk), catheterizations causing direct injury
  • factors affecting the properties of the blood
    estrogen-containinghormonal contraception
    genetic thrombophilia
    acquired thrombophilia
    cancer (due to secretion of pro-coagulants)