CHAPTER 57 Venous Thromboembolism and Pulmonary Embolism
Nan Li and Hooman Poor
Icahn School of Medicine at Mount Sinai, New York, NY, USA
Definition of disease
VTE is defined as a blood clot, or thrombosis, that forms in a vein which may or may not break off into emboli. In the critically ill, the most important manifestations are deep vein thrombosis (DVT) and acute pulmonary embolism (PE).
DVTs can occur in any extremity, and when they occur in the lower extremity they are classified as distal if they involve the calf veins and proximal if they involve the popliteal, femoral, or iliac veins.
Acute PEs can vary in size and location within the pulmonary vasculature but are classified by hemodynamic manifestations.
Massive PE is defined as acute PE with hemodynamic instability (i.e. hypotension, shock, cardiac arrest), sub‐massive PE is defined as acute PE without hypotension but with evidence of right ventricular dysfunction, and low risk PE is defined as acute PE not classified as either massive or sub‐massive.
Since DVT and PE represent a spectrum of one disease, there is a close relationship between incidence of DVT and PE in the ICU population.
In the absence of mechanical and chemoprophylaxis, the incidence of DVT in the ICU varies from 10% to 30% in medical/surgical units versus up to 60% in trauma patients.
With routine use of mechanical and anticoagulant prophylaxis, the risk of symptomatic DVT is as low as 1–12%.
PE occurs in up to 50% of patients with a proximal DVT. Additionally, about 80% of patients who present with an acute PE have evidence of DVT in the legs.
Thrombi usually form in venous valve pockets or other sites of venous stasis. Although the specific etiology varies depending on the underlying disease state, there is a common theme of venous stasis, endothelial injury, and/or hypercoagulability that leads to clot formation.
Thrombi that form in the deep veins of the lower extremities can propagate proximally. More proximal thrombi, especially above the popliteal level, are at higher risk for embolization.
Thromboemboli travel towards the heart via the inferior vena cava, enter through the right side of the heart and continue into the pulmonary arteries.
Depending on clot size, anatomic location, acuity of disease, and baseline cardiopulmonary reserve, the resultant pulmonary emboli can lead to a wide variety of clinical symptoms, ranging from being asymptomatic to dyspnea, hypoxemia, chest pain, hemodynamic collapse, and even sudden death.
Risk factors for thrombi formation fall under three broad categories: venous stasis‐promoting states, intrinsic hypercoagulable states, and direct injury or trauma.
There are many acquired and hereditary factors that promote a hypercoagulable state, conferring an increased risk for VTE. For hospitalized patients, the risk is further compounded by additional factors such as immobility, acute medical illness, and possible surgical procedures.
Important risk factors for VTE to consider in the critically ill population are listed here.
Age >75 years
Acute infectious disease
Acute respiratory failure
Indwelling central venous catheter
Chronic care facility
Malignancy without chemotherapy
Malignancy with chemotherapy
Prior central venous catheter or transvenous pacing
Neurologic disease with extremity paresis
The ICU‐VTE score can be used to classify critically ill patients as low, medium, or high risk for developing DVT, PE, or both (Table 57.1).
Table 57.1ICU‐VTE scoring system for risk of developing DVT and/or PE.
Prior history of VTE
Platelet count on hospital admission >250 000/μL
Central venous catheterization
Bedbound ≥4 days
Invasive mechanical ventilation
Lowest hemoglobin level during admission ≥9 g/dL
Maximum total score
VTE risk category
Risk of symptomatic VTE
Thromboprophylaxis against VTE is indicated and necessary for all hospitalized critically ill patients. The methods of prophylaxis range from mechanical (intermittent compression devices or compression stockings) to pharmacologic (unfractionated heparin or low molecular weight heparin), or a combination of both. The type of prophylaxis depends on the individual VTE risk for each patient.
Current guidelines recommend against routine screening for DVT in the critically ill population. Rather, several risk assessment models have been developed to categorize patients into low, medium, or high risk populations based on risk factors and to assist in deciding what kind of prophylaxis is most appropriate. Consensus statements recommend all hospitals formulate their own written guidelines for risk assessment of every inpatient.
The American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis clinical practice guidelines outline evidence‐based practice recommendations for thromboprophylaxis in different medical settings.
In general, pharmacologic prophylaxis with low dose unfractionated heparin (LDUH) and low molecular weight heparin (LMWH) has been shown to be effective and safe in medical patients. Both LDUH (5000 U SC either twice or three times daily dosing) and LMWH (enoxaparin 40 mg SC daily) reduce the risk of DVT and PE by more than 50%.
Bleeding risk (e.g. in planned surgical procedure or acquired coagulopathy) is important to consider and may be a relative contraindication for anticoagulant prophylaxis. Other common contraindications include hypersensitivity to heparin products, heparin‐induced thrombocytopenia (HIT), epidural anesthesia, hemorrhagic stroke, and renal insufficiency.
Though less effective, the use of mechanical prophylaxis such as intermittent sequential devices or graduated compression stockings is recommended in addition to chemoprophylaxis, or alone if there is a contraindication to anticoagulant prophylaxis.
Inferior vena cava (IVC) filters are not indicated for primary prophylaxis.
DVT or PE recurrence occurs as a result of discontinuation of anticoagulation or from treatment failure.
Duration of anticoagulation therapy differs depending on the mechanism of VTE formation. Provoked VTE events may only require therapy for a limited time whereas unprovoked VTE events may require lifelong anticoagulation.
Because previous VTE is an independent risk factor for developing a new VTE event and risk of recurrence is high regardless of whether the VTE was provoked or unprovoked, clinical suspicion for recurrence must remain high.
Critical illness alone can lead to a hypercoagulable state, and combined with patient‐specific risk factors, clinical suspicion must remain high for a hospitalized patient who becomes acutely critically ill.
Classic exam findings for DVT include an asymmetrically swollen extremity, warmth, or tenderness. PE typically presents with acute onset pleuritic chest pain, dyspnea, tachycardia, or hypoxemia. It is important to note that in the critically ill, DVTs can remain asymptomatic and PEs can progress rapidly from minimal symptoms to hemodynamic collapse.
CT angiography (CTA) is the gold standard for diagnosis of PE, but its use may be limited by a patient’s medical stability or renal function. A ventilation–perfusion (V/Q) scan is an alternate testing option if renal function precludes CTA. Venous ultrasonography is the gold standard for DVT diagnosis and carries minimal risk.
DVT Infectious cellulitis
Warm, tender, erythematous extremity; associated with fever and leukocytosis
Pain, induration, erythema along course of a superficial vein
Non‐pitting edema with dermal thickening; assess for history of malignancy or lymph node dissection
PE Acute coronary syndrome
Pressure‐like chest pain, elevated cardiac enzymes with ST abnormalities on ECG
CXR is diagnostic; bedside lung ultrasound shows absence of lung sliding
Pneumonia or thoracic mass
CXR with focal opacity or mass with obstruction; may present with infectious symptoms
Congestive heart failure
CXR with evidence of vascular congestion, elevated B‐type natriuretic peptide (BNP)
COPD or asthma exacerbation
Wheezing on exam, improvement with bronchodilator or steroid therapy
A lower extremity DVT may present with asymmetric leg pain, warmth, or swelling; however, most DVTs are asymptomatic.
Acute PE often presents with acute onset dyspnea or chest pain. Pleurisy and hemoptysis can also occur, and is commonly associated with pulmonary infarction.
Massive PE manifests as hemodynamic instability and can lead to death.
Signs and symptoms of DVT and PE are suggestive, but none are sensitive or specific. Thus, if suspicion is high, further diagnostic testing is required.
It is important to ascertain any patient‐specific comorbidities that may increase the risk for a VTE such as history of malignancy, prolonged immobility, or recent trauma.
A personal history of prior DVT or PE is most important as it confers one of the highest risks for a new VTE event.
Physical exam features of DVT and PE are non‐specific and non‐diagnostic so it is important to perform further diagnostic testing in appropriate patients.
For the diagnosis of acute DVT, the exam may show swelling and tenderness of the extremity but often there are no significant physical exam findings.
The cardiac exam is important for initial assessment of acute PE because right ventricular (RV) strain from acute pulmonary hypertension is a serious complication. Exam findings include jugular venous distention, a loud P2, RV heave, or a right‐sided gallop. ECG abnormalities include sinus tachycardia, S1Q3T3 pattern, right bundle branch block, or right axis deviation.
RV strain can also be assessed via bedside point‐of‐care echocardiography to qualitatively assess RV size and function.
Acute PE can also cause acute obstructive shock which manifests as hypotension with cool extremities and a narrow pulse pressure.
Disease severity classification
Once the diagnosis of acute PE has been made, it is important to risk stratify the patient into low, intermediate, or high risk categories in order to guide medical decision making.
The pulmonary embolism severity index (PESI, https://www.mdcalc.com/pulmonary‐embolism‐severity‐index‐pesi) is a validated prognostic scoring system that predicts 30 day mortality and is useful to guide initial management of acute PE, particularly for the management of very low risk patients. This clinical prediction rule uses 11 patient characteristics that are independently associated with mortality to classify patients into five severity classes of increasing mortality.
History of cancer.
History of heart failure.
History of chronic lung disease.
Heart rate ≥110/min.
Systolic blood pressure ≤100 mmHg.
Respiratory rate >30.
Temperature ≤36°C (96.8°F).
Altered mental status.
O2 saturation <90%.
List of diagnostic tests
For the hospitalized or ICU patient, d‐dimer for the diagnosis of DVT or PE is rarely useful, as it is often positive in patients with infection, cancer, trauma, or other inflammatory states.
Important laboratory tests include B‐type natriuretic peptide (BNP) and troponin levels as these are good surrogates for RV strain and cardiac ischemia, respectively. Presence of RV strain or cardiac ischemia increases the risk for acute decompensation and thus may affect decisions about therapy.
A coagulation panel should also be obtained as a monitoring parameter for anticoagulation initiation.
List of imaging techniques
Imaging is crucial to the diagnosis of VTE. The choice and timing of imaging modality is dependent on the stability of the patient.
In general, venous ultrasonography is the gold standard for DVT diagnosis and CTA is the gold standard for PE diagnosis.
In hemodynamically stable patients with high risk for PE, a CTA is sufficient for diagnosis as it has a very high negative predictive value of 95%.
If CTA cannot be done due to contraindication to intravenous contrast (i.e. allergic reaction or renal insufficiency), a V/Q scan is an alternative. A V/Q scan also has a high negative predictive value of 97%, but is diagnostic in only 30–50% patients with suspected PE.
If suspicion for PE is high with known DVT found on venous ultrasonography, then CTA can be avoided and treatment can be initiated.
In hemodynamically unstable patients with suspicion for PE, CTA is the imaging modality of choice.
Clinical stability may limit timing or ability of obtaining CTA; therefore, transthoracic echocardiography (TTE) is an important adjunct imaging technique.
TTE is useful to assess for RV strain in the setting of acute PE causing hemodynamic instability or shock.
Transesophageal echocardiography (TEE) can also be done to visualize emboli in the main pulmonary arteries.
Potential pitfalls/common errors made regarding diagnosis of disease
In critically ill patients, accurate and timely diagnosis is vital. Given CT imaging is now available widely, clinicians have come to rely more heavily on CTA for diagnosis, but there are many pitfalls in CTA.
Timing of imaging is a concern given the need to transport a patient to the scanner. Often, in the ICU setting, a patient’s clinical stability may preclude safe transport.
ICU patients often have renal insufficiency that also precludes CT imaging.
Bedside ultrasound in the form of point‐of‐care echocardiography and lower extremity venous compressive ultrasound are excellent adjuncts to aid in diagnosis, and are often underutilized.
Bedside ultrasound can be readily done, presents very little risk to the patient, and gives real time data that can rapidly inform treatment decisions.
The mainstay of treatment for VTE is systemic anticoagulation.
For hospitalized patients, LMWH or unfractionated heparin (UFH) is most commonly used as first line treatment as it has a relatively short half‐life and can reach therapeutic levels within a few hours.
For patients with high clinical suspicion for VTE, empiric anticoagulation (usually with UFH) should be started while awaiting results from diagnostic tests.
In patients presenting with hemodynamic instability or shock, initiation of vasopressors and inotropes is indicated.
The preferred vasopressor is norepinephrine and the preferred inotrope is dobutamine.
It is prudent to avoid excessive intravenous fluid administration as it may worsen RV function and lead to further hypotension and clinical decline.
Systemic thrombolytic therapy is indicated in patients with acute PE and hemodynamic instability.
For patients who are hemodynamically unstable or in cardiac arrest, systemic thrombolysis is indicated.
For patients who are hemodynamically stable, but with evidence of significant RV dysfunction, the decision for thrombolytic therapy should be made on a case by case basis by a multidisciplinary team. Low dose, catheter‐directed thrombolysis has been shown to be effective in this population, but evidence is limited.
In patients presenting with shock or cardiac arrest, surgical pulmonary embolectomy may be indicated if there is contraindication to thrombolysis or failure of thrombolysis (Figures 57.1 and 57.2).
IVC filters are indicated when there is an absolute contraindication to anticoagulation or with treatment failure. IVC filters should not be routinely used as first line therapy.
5000 unit IV bolus, followed by 18 units/kg/h infusion
Target aPTT to institution protocol
1 mg/kg SC twice daily
<50 kg: 5 mg SC daily
50–100 kg: 7.5 mg SC daily
>100 kg: 10 mg SC daily
tPA 100 mg IV over 2 hours
Low dose, catheter‐directed thrombolysis:
Catheter placement via femoral vein into both right and left pulmonary arteries
Slow infusion of low dose thrombolytic via catheter localized to pulmonary arteries given over 15 hours
LMWH and fondaparinux dosing is limited by renal function
Bleeding risk must be assessed when giving thrombolytic therapy Low‐dose, catheter‐directed therapy is appropriate for patients with PE exhibiting hemodynamic stability and evidence of significant RV dysfunction, but given lack of strong evidence, decision should be made by multidisciplinary team
Surgical Pulmonary artery embolectomy:
Requires placing patient on emergent cardiopulmonary bypass
Open thoracotomy versus minimally invasive approach to access the main pulmonary arteries and retrieve clot
Placement in infrarenal IVC
Appropriate for patients in cardiac arrest, refractory shock despite thrombolysis, or with contraindication to thrombolysis
Prevention/management of complications
The most important complication of VTE treatment is bleeding. Therefore, systemic anticoagulation requires frequent monitoring, especially in the ICU as critical illness can also promote coagulopathy. Additionally, UFH should be used when possible as it has a shorter half‐life and can be reversed if necessary.
HIT is a serious complication of heparin therapy and can lead to significant morbidity and mortality. Close monitoring of platelet count as well as coagulation factors is recommended.