venous%20thromboembolism%20-%20management
VENOUS THROMBOEMBOLISM - MANAGEMENT
Deep vein thrombosis is a frequent manifestation of venous thromboembolism in which there is a blood clot blocking a deep vein.
Clinical findings are important to the diagnosis of deep vein thrombosis but are poor predictors of the presence or severity of thrombosis.
Pulmonary embolism is the blockage of the blood vessels in the lungs usually due to blood clots from the veins, especially veins in the legs and pelvis.
Dyspnea, pleuritic chest pain, syncope and tachypnea occur in most cases of pulmonary embolism.
Massive pulmonary embolism has the prime symptom of dyspnea and systemic arterial hypotension that requires pressor support is the predominant sign.

Diagnosis

  • 1st-line diagnostic tests [eg electrocardiogram (ECG), chest X-ray (CXR) and arterial blood gases (ABG)] are indicated to assess clinical probability of pulmonary embolism (PE) and general condition of patient

Recommended Diagnostic Tests based on Clinical Pretest Probability Result:

  • Low pretest probability: D-dimer, duplex venous ultrasonography (DUS) with compression, venography, whole-leg ultrasonography (US)
  • Moderate pretest probability: D-dimer, proximal DUS with compression, venography, whole-leg US
  • High pretest probability: Proximal DUS with compression, whole-leg US, venography

Evaluation

Deep Vein Thrombosis (DVT)

Clinical findings are important to the diagnosis of DVT but are poor predictors of the presence or severity of thrombosis

  • Pretest probability is needed to guide the diagnostic process
  • Wells Scale of Clinical Pretest Probability for Deep Vein Thrombosis (DVT)

    Clinical Features

    Points

    Score

    Entire leg swollen

    1.0

    High-risk

    ≥3

    Calf swollen by >3 cm compared to the asymptomatic (measured 10 cm below tibial tuberosity)

    1.0

    Moderate-risk

    1-2

    Localized tenderness along the deep venous system distribution

    1.0

    Low-risk

    ≤0

    Pitting edema (greater in the symptomatic leg)

    1.0

    If both legs are symptomatic, score the more severe side

    Collateral superficial veins (non-varicose)

    1.0

    Immobilization in prior 4 days or major surgery within 4 weeks

    1.0

    Paralysis, paresis, recent plaster immobilization of lower extremity

    1.0

    Active cancer (ongoing treatment or within the last 6 months or palliative)

    1.0

    Alternative diagnosis as likely or greater than that of DVT

    -2.0

    Modified from: Institute for Clinical Systems Improvement. Health care guideline: venous thomboembolism diagnosis and treatment. 13th ed. January 2013.

Pulmonary Embolism (PE)

Clinical Evaluation

  • Evaluating the likelihood of PE in an individual patient according to the clinical presentation is of utmost importance in the interpretation of diagnostic test results and the selection of an appropriate diagnostic strategy
  • A reasonable clinical suspicion is required to avoid missing the diagnosis of PE
  • Clinical evaluation is accurate to discriminate a subgroup of patients with a low likelihood of PE
  • Clinical probability may be estimated empirically or explicitly by a prediction rule
  • All patients with possible PE should have clinical probability assessed and documented
  • Patients should also be evaluated for risk factors for VTE
  • Clinical evaluation is accurate to discern whether patient is of low likelihood of PE
  • Patients that have low clinical probability of PE, no lower limb DVT and nondiagnostic lung scan have low risk of PE

Massive Pulmonary Embolism

  • In patients with suspected massive pulmonary embolism who are too unstable for lung imaging, right ventricular dysfunction can usually be found at the bedside
    • Left parasternal heave, distended jugular veins and systolic murmur of tricuspid regurgitations that increases with inspiration

Sub-Massive Pulmonary Embolism 

  • Subgroup of non-massive PE patients who present with the following:
    • Normal blood pressure (BP), normal tissue perfusion and clinical or echocardiographic evidence of right ventricular dysfunction
    • Elevation troponin, pro-BNP or BNP

Low-Risk Pulmonary Embolism 

  • Most useful initial test which typically shows indirect signs of acute pulmonary hypertension and right ventricular overload
  • if acute PE is the cause of the hemodynamic changes
  • If patient is unstable, thrombolytic treatment or surgery can be done based only on compatible echocardiography findings
  • If patient has been stabilized, a definitive diagnosis should be pursued
    • Lung scan, sCT and bedside transesophageal echocardiography (TEE) are usually able to confirm diagnosis
    • Normal lung scan or sCT angiogram suggests that another cause of shock should be found
  • In patients with suspected massive PE who are too unstable for lung imaging, right ventricular dysfunction can usually be found at the bedside
    • Left parasternal heave, distended jugular veins and systolic murmur of tricuspid regurgitations that increases with inspiration

Pretest Probability of Pulmonary Embolism

  • There are 2 frequently used Pretest Probability of PE: Geneva score (Europe) and Wells scale (Canadian rule)
Geneva Score
  • Requires arterial blood gas measurement and a chest radiograph
Wells Scale
  • Requires that the patient has clinical features suggestive of PE (eg breathlessness, and/or tachypnea with or without pleuritic chest pain and/or hemoptysis)
  • Along with 2 other features
    1. The absence of another reasonable clinical explanation
    2. The presence of a major risk factor

    Wells Scale of Clinical Pretest Probability for Pulmonary Embolism (PE)

    Clinical Features

    Points

    Pretest Probability

    Total Points

    Clinical signs and symptoms of DVT

    = 3.0

    Based on likelihood of pulmonary embolism (PE)

    Alternative diagnosis is less likely than PE

    = 3.0

    PE less likely

    4

    Heart rate >100 beats/minute

    = 1.5

    PE likely

    >4

    Immobilization in the last 4 days

    = 1.5

    According to risk groups

    Previous DVT/PE

    = 1.5

    High

    >6

    Hemoptysis

    = 1.0

    Intermediate

    3-6

    Malignancy (with treatment within the last 6 months)

    = 1.0

    Low

    <2

    Modified from: Institute for Clinical Systems Improvement. Health care guideline: venous thomboembolism diagnosis and treatment. 13th ed. January 2013.
Pulmonary Embolism Rule-Out Criteria (PERC)
  • Use to identify group at very low risk of PE
  • If the patient has answered yes in any of the following questions, the patient is Pulmonary Embolism Rule-Out Criteria (PERC) positive:
    • Is the patient >49 years?
    • Is the patient’s heart rate >99 beats/minute?
    • Is the patient’s pulse oximetry reading <95% while breathing room air?
    • Does the patient have hemoptysis?
    • Is the patient on exogenous estrogen? Does the patient have prior diagnosis of VTE?
    • Has the patient had surgery or trauma in the previous 4 weeks?
    • Does the patient have unilateral leg swelling at the calves?

Assessment

Massive Pulmonary Embolism
  • In patients who are too unstable for lung imaging, right ventricular (RV) dysfunction can usually be found at the bedside
    • Left parasternal heave, distended jugular veins and systolic murmur of tricuspid regurgitations that increases with inspiration
    • Electrocardiogram (ECG) may show new right bundle branch block or other evidence of right ventricular strain (eg inverted T waves in leads V1-V4)

Laboratory Tests

  • Lab results can be normal but some abnormal findings increase the suspicion for PE

Arterial Blood Gas (ABG)

  • Can show hypoxemia, hypocapnia and widened (A-a) O2 difference

Electrocardiogram (ECG)

  • Can show right axis deviation, supraventricular arrhythmia, S1Q3T3 pattern or P-pulmonale, sinus tachycardia, or a normal tracing

B-type Natriuretic Peptide (BNP) and Troponin

  • Consider in a patient with substantial clot burden, abnormal echocardiogram or clinical findings suggestive of PE
  • Elevated BNP and troponin are associated with right ventricular (RV) strain and increased mortality even in the absence of hemodynamic instability

Plethysmography

  • Computerized strain gauge plethysmography
    • Rapid and easy to perform
    • Has shown a sensitivity of 90% for proximal DVT (popliteal, femoral, or iliac vein) and 66% for distal (calf vein) DVT 
  • Impedance Plethysmography (IPG)
    • Normal finding with serial IPG is associated with a low risk of clinically important PE (<1%) or recurrent venous thrombosis (2%)
    • Serial testing with IPG for 10-14 days appears to be effective for identifying patients with extending calf DVT

Imaging

Chest X-ray

  • May demonstrate atelectasis, pleural-based infiltrates or effusions or rarely engorged central pulmonary artery associated with a paucity of peripheral vessels
  • Near-normal radiographic results with severe respiratory compromise is highly suggestive of massive PE
  • Westermark sign (focal oligemia) may indicate massive central embolic occlusion
  • Hampton lump, a peripheral wedge-shaped density above the diaphragm, usually signifies pulmonary infarction

Ventilation-Perfusion Lung Scanning (V/Q Scan)

  • Normal or near-normal lung scans are sufficient to exclude PE, regardless of pretest probability
  • Low probability scans in combination with a low pretest probability make probability of PE low
  • High probability scans provide the predictive power to establish diagnosis in context of reasonable suspicion of PE 
Venous Ultrasonography (US)
  • Most pulmonary emboli arise from the deep veins of the legs thus it is rational to search for a residual DVT  in suspected PE patients
  • Normal ultrasonographic exam of the leg veins does not rule out PE 
  • US studies may have false positive or may detect residual abnormalities from past VTE
    • Only definite positive studies under certain clinical circumstances (eg patient without history of VTE but has a high clinical probability of PE) should serve as a basis for the start of therapy
  • Used to improve estimation of the clinical probability of PE and avoid more invasive testing in patients with a negative lung imaging study

Duplex Venous Ultrasonography (DUS)

  • B-mode, (eg 2D) imaging and pulse-wave Doppler interrogation
  • Primary radiologic device for the evaluation of proximal DVT
    • Most often used non-invasive test to diagnose DVT in patients with moderate or high clinical pretest probability
    • Has a very high sensitivity and specificity for diagnosing proximal DVT in symptomatic patients, but less favorable results for calf vein and asymptomatic DVT 
    • The primary diagnostic criteria to establish the presence of DVT by ultrasonography is incomplete vein compressibility
  • Combined use of clinical pretest probability and duplex ultrasonography (with compression) is effective in confirming or excluding the diagnosis of DVT
    • In patients with clinical suspicion of DVT , positive D-dimer and negative ultrasonography, consider repeat ultrasonography for suspected calf thrombosis or venography for suspected proximal thrombosis in 3-7 days
  • In patients with negative computed tomographic pulmonary angiography (CTPA) results and positive D-dimer and a PE likely clinical probability, further evaluation with DUS should be used to improve clinical likelihood of diagnosing disease and avoid more invasive testing 
    • A positive result confirms the diagnosis of DVT and requires treatment regardless of the presence or absence of PE 
    • A negative result, incorporation of CTPA can improve diagnostic accuracy and potentially avoid unnecessary pulmonary angiography
Echocardiography
  • Most useful initial test which typically shows indirect signs of acute pulmonary hypertension and right ventricle (RV) overload if acute PE is the cause of the hemodynamic changes
  • If patient is unstable, thrombolytic treatment or surgery can be done based only on compatible echocardiography findings
  • If patient has been stabilized, a definitive diagnosis should be pursued
    • Lung scan, spinal computed tomography (sCT) and bedside transesophageal echocardiography (TEE) are usually able to confirm diagnosis
    • Normal lung scan or sCT angiogram suggests that another cause of shock should be found
  • Useful for rapid triage in acutely ill patients with suspected massive PE
    • Usually reliable to differentiate between illnesses that have radically different treatments compared to PE (eg AMI, pericardial tamponade, infective endocarditis, aortic dissection, etc)
    • May suggest/reinforce clinical suspicion of PE with the findings of right ventricular (RV) overload and dysfunction in the presence of Doppler signs of increased pulmonary arterial pressure
    • May also definitively confirm diagnosis of PE by visualization of proximal pulmonary arterial thrombi
  • It has not been confirmed that echocardiography can identify patients who would benefit from thrombolytic therapy if they present without shock or hypotension

Magnetic Resonance Imaging (MRI)

  • Provides morphological and functional information about lung perfusion and right heart function but compared to CT scan, MRI needs improvement in the image quality
  • Useful in patients with suspected thrombosis of the superior and inferior vena cava or pelvic veins; should be deferred in patients with suspected first lower extremity DVT
  • Has a similar diagnostic accuracy to that of ultrasonography for assessing proximal DVT
Magnetic Resonance Angiography (MRA)
  • MRA appears to be promising in human and animal models
  • It avoids ionizing radiation but has a poor sensitivity for subsegmental clots and limited access is likely to continue for several years

Spiral Computed Tomography (sCT) Scan

  • Has shown promise for the diagnosis of DVT and other soft tissue diseases in patients with leg swelling
  • Visualizes proximal obstructions and common, superficial and deep femoral veins

Computed Tomographic Pulmonary Angiography (CTPA)

  • Recommended as the initial lung imaging modality for non-massive PE 
  • Increasingly used as an adjunct or alternative to other imaging modalities and is superior in specificity to ventilation-perfusion isotope scanning
  • A positive CTPA with PE likely clinical pretest probability, is confirmed positive for PE and no further diagnostic testing is needed
  • Enables direct visualization of the pulmonary emboli and may provide information about parenchymal abnormalities that might help to establish an alternative diagnosis
  • More useful for patients with underlying cardiac disease, chronic obstructive pulmonary disease (COPD) or asthma
  • Has a high specificity and sensitivity for central clots
  • The main disadvantage of CTPA to that of conventional pulmonary angiography is that subsegmental clot is less likely to be seen
  • Patients with a good quality negative CTPA do not require further investigation or treatment for PE 
Conventional Pulmonary Angiography
  • Historically considered the gold standard for the diagnosis of PE 
  • Limitations include requirement of expertise in performance and interpretation, it is invasive and there are associated risks
    • With subsegmental clot, there can be inter-observer disagreement in up to 1/3 of cases
  • Angiography should be reserved for patients in whom non-invasive tests remain inconclusive or are not available
  • Use of pulmonary angiography may also depend on patient’s clinical status and necessity to obtain an absolute diagnosis

Contrast Venography

  • The gold standard for establishing the diagnosis of DVT 
    • Offers precise detail of the venous anatomy and the ability to reliably exclude thrombosis in the calf
    • Can help distinguish between old and new clots
  • Excellent for calf veins, but it is an invasive procedure, not always technically possible and carries a small risk of an allergic reaction/venous thrombosis
    • Other disadvantages include cost, patient discomfort, significant resource use, availability, requirement for foot vein cannulation, intravenous contrast use and possibility of secondary thrombi
    • In some countries, its use has been supplanted by venous ultrasonography
    • Generally reserved for difficult diagnostic cases

Screening

 D-dimer 

  • A highly sensitive but a nonspecific screening test for the presence of PE
    • Sensitivity may be decreased if the duration of VTE manifestations is >2-3 days prior to testing and/or if the patient is on Heparin
    • Best used for evaluation of outpatients in the emergency department
  • A negative D-dimer test via any D-dimer method (SimpliRED, Vidas or MDA) reliably excludes PE in patients with low clinical probability, such patients do not require imaging for VTE 
  • A negative D-dimer test using ELISA (Vidas) or MDA methods reliably excludes PE in patients with intermediate probability
  • A positive D-dimer requires further evaluation to exclude PE adequately
    • However, raised levels of D-dimer do not confirm the presence of VTE because such levels are found in hospitalized patients, obstetrics including postpartum period, peripheral vascular disease, cancer and many inflammatory diseases as well as increasing age
  • Cardiovascular D-dimer should not be performed in those with high clinical probability of PE 
  • D-dimer is inappropriate for suspected VTE with recent surgery or trauma and should proceed directly to radiologic studies eg duplex ultrasonography (US) or computed tomographic pulmonary angiography (CTPA)

D-dimer Level by Enzyme-Linked Immunosorbent Assay (ELISA)

  • A highly sensitive but nonspecific screening test for the presence of VTE 
    • D-dimer levels may also be elevated in patients with myocardial infarction (MI), sepsis, cancer, inflammation, infection, necrosis, etc
    • Therefore, high concentration of D-dimer has a poor positive predictive value for DVT and cannot be used to rule in the disease 
  • Normal D-dimer level by ELISA assay (<500 ng/mL) has a high negative predictive value and is useful to rule out VTE thus reducing the need for imaging when used in conjunction with clinical probability, plethysmography, or ultrasonography
    • Patients with a low clinical pretest probability of DVT and a negative D-dimer assay are considered to have no DVT or have a very low risk of subsequent DVT and can be followed up clinically without further testing unless new or progressive symptoms develop
  • This is most useful in ED patients, in ambulatory care settings and in patients with recent onset of symptoms who are not currently taking anticoagulants
    • Can be used after a negative duplex US to determine the need for further radiologic evaluation
    • In elderly or inpatients, the D-dimer retains a high negative predictive value but is normal in <10% of patients and therefore is not useful in these patients

Contraindications

  • Absolute contraindications to thrombolysis in a life-threatening situation are rarely a factor for treatment

Absolute Contraindications

  • Hemorrhagic stroke or stroke of unknown origin at any time
  • Recent major trauma, surgery, or head injury in the past 3 weeks
  • Ischemic stroke within the past 6 months
  • CNS damage or tumors
  • GI bleeding within the last month
  • Known increased risk for bleeding

Relative Contraindications

  • Transient ischemic attack within the past 6 months
  • Puncture of a non-compressible vessel
  • Uncontrolled severe hypertension (SBP >180 mmHg, DBP >100 mmHg)
  • Neurosurgery or ophthalmologic surgery within the last 1 month
  • Ischemic stroke within the last 2 months
  • GI bleeding within the last 10 days
  • Active peptic ulcer disease
  • Recent traumatic cardiopulmonary resuscitation
  • Pregnancy or within 1 week postpartum
  • Infective endocarditis
  • Oral anticoagulant therapy
  • Advanced liver disease
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Cardiology - Malaysia digital copy today!
DOWNLOAD
Editor's Recommendations
Most Read Articles
5 days ago
Higher circulating levels of docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) appear to be protective against incident atherothrombotic and cardioembolic strokes, respectively, according to a recent study.
Roshini Claire Anthony, 11 Oct 2017

The prevalence of resistant hypertension may be lower than expected, particularly once pseudo-resistant hypertension due to treatment nonadherence is taken into account, according to a presentation at the recent APCH 2017.

Pank Jit Sin, 07 Jan 2015

Cardiovascular diseases (CVD) have been the main cause of death in the Malaysian population since 2007. This trend has continued, with the number of people dying from CVD-related causes increasing year on year. 

Tristan Manalac, 12 Oct 2017
Administration of a long-acting medication at the time that is most suitable for maximum patient compliance is the best approach in controlling blood pressure, said Dr. Trefor Morgan at the recently concluded 13th Asian-Pacific Congress of Hypertension (APCH 2017), held at the Suntec Singapore Convention and Exhibition Centre.