D-Dimer is the Degradation Product of Cross-Linked Fibrin
D-Dimer is Easy to Obtain
However, D-Dimer May Be Elevated in Conditions Other Than Venous Thromboembolism
“Sensitive” D-Dimer Assays: quantitative or semiquantitative newer generation assays
Rapid Enzyme-Linked Immunosorbent Assay (ELISA)
Immunoturbidimetric Assay
Latex Agglutination Assay
Interpretation
Normal D-Dimer Level: <500 ng/mL (<0.5 μg/mL or <500 μg/L) Fibrinogen Equivalent (FE) Units
Age-Adjusted D-Dimer Thresholds Have Also Been Suggested to Decrease Unnecessary Imaging, But Have Not Widely Adopted in Clinical Practice (Ann Intern Med, 2016) [MEDLINE]
Clinical Efficacy
ANTELOPE Study (Am J Respir Crit Care Med, 2002) [MEDLINE]
The Sensitivity of D-Dimer was Lower in Subsegmental Pulmonary Embolism (53%), as Compared to Large Main, Lobar, and Segmental Pulmonary Embolism (93%)
Systematic Review of D-Dimer in the Diagnosis of Venous Thromboembolism (Ann Intern Med, 2004) [MEDLINE]
For the Diagnosis of Deep Venous Thrombosis (DVT)
Enzyme-linked Immunosorbent Assay (ELISA) D-Dimer Assay Had a 96% Sensitivity (95% CI: 0.91-1.00) and Negative Likelihood Ratio of 12% (95% CI: 0.04-0.33)
Quantitative Rapid Enzyme-linked Immunosorbent Assay (ELISA) D-Dimer Assay Had a 96% Sensitivity (95% CI: 0.90-1.00) and Negative Likelihood Ratio of 9% (95% CI: 0.02-0.41)
For the Diagnosis of Pulmonary Embolism (PE)
Enzyme-linked Immunosorbent Assay (ELISA) D-Dimer Assay Had a 95% Sensitivity (95% CI: 0.85-1.00) and Negative Likelihood Ratio of 13% (95% CI: 0.03-0.58)
Quantitative Rapid Enzyme-linked Immunosorbent Assay (ELISA) D-Dimer Assay Had a 95% Sensitivity (95% CI: 0.83-1.00), and Negative Likelihood Ratio of 13% (95% CI: 0.02-0.84)
Emergency Department Study of the Use of Age-Adjusted D-Dimer Thresholds (Chest, 2014) [MEDLINE]
Use of Age-Adjusted D-Dimer Threshold Decreased Imaging Among Patients >50 y/o with a Revised Geneva Score ≤10
Although the Adoption of an Age-Adjusted D-Dimer Threshold is Probably Safe, the Confidence Intervals Surrounding the Additional 1.5% of Pulmonary Emboli Missed Necessitate Prospective Study Before this Practice Can Be Adopted into Routine Clinical Practice
European ADJUST-PE Study of Age-Adjusted D-Dimer Levels in the Diagnosis of Pulmonary Embolism (JAMA, 2014) [MEDLINE]
Age-Adjusted D-Dimer (Only for Patients ≥50 y/o): defined as 10 x age
Compared with a Fixed D-Dimer Cutoff of 500 μg/L (500 ng/mL), the Combination of a Pre-Test Clinical Probability Assessment and Age-Adjusted D-Dimer Cutoff was Associated with a Larger Number of Patients in Whom Pulmonary Embolism Could Be Considered Ruled Out with a Low Likelihood of Subsequent Clinical Venous Thromboembolism
Retrospective Study of the Use of Age-Adjusted D-Dimer Thresholds in the Emergency Department (Ann Emerg Med, 2016) [MEDLINE]
An Age-Adjusted D-Dimer Limit Has the Potential to Reduce Chest Imaging Among Older Emergency Department Patients and is More Accurate than a Standard Threshold of 500 ng/dL
Systematic Review of D-Dimer in the Diagnosis of Pulmonary Embolism (Cochrane Database Syst Rev, 2016) [MEDLINE]: n = 1585 (total of 4 studies)
Sensitivity: 80-100%
Specificity: 23-63%
High Levels of False-Positive Results were Observed, Especially Among Patients >65 y/o
A Negative D-Dimer is Valuable in Ruling Out Pulmonary Embolism in Patients Who Present to the Ambulatory/Emergency Setting with a Low Pre-Test Probability for Pulmonary Embolism
Evidence from One Study Suggests that D-Dimer May Have Less Utility in Older Patient Populations, But No Empirical Evidence was Available to Support an Increase in the Diagnostic Threshold of Interpretation of D-Dimer Results for those >65 y/o
Systematic Review and Meta-Analysis of Wells Criteria and D-Dimer Testing in the Diagnosis of Pulmonary Embolism (Ann Intern Med, 2016) [MEDLINE]
In Patients with an “Unlikely” Pre-Test Probability of Pulmonary Embolism, Age-Adjusted D-Dimer Testing is Associated with a 5% Increase in the Proportion of Patients with Suspected Pulmonary Embolism in Whom Imaging Can Be Safely Withheld, as Compared to Fixed D-Dimer Testing
Systematic Review and Meta-Analysis of 6 Prospective Studies of Age-Adjusted D-Dimer Thresholds (Ann Intern Med, 2016) [MEDLINE]
Age-Adjusted D-Dimer Testing is Associated with a 5% Absolute Increase in the Proportion of Patients with Suspected Pulmonary Embolism in Whom Imaging Can Be Safely Withheld Compared with Fixed D-Dimer Testing
This Strategy Seems Safe Across Different High-Risk Subgroups, But its Efficiency Varies
If the Pre-D-Dimer Probability of PE is 15% (Intermediate Pre-Test Probability), Only a D-DImer <500 ng/mL Will Result in a Post-Test Probability <3%
Consequently, Given a Pre-Test Probability of 15% (Intermediate Pre-Test Probability) and a CT Pulmonary Artery Angiogram Threshold of 3%, a Strategy to Obtain CT Pulmonary Artery Angiogram for D-Dimer ≥500 ng/ mL is Consistent with the Interval Likelihood Ratios Reported
Study of Age-Adjusted D-Dimer Threshold to YEARS Algorithm in the Diagnosis of Pulmonary Embolism ( J Thromb Haemost, 2017) [MEDLINE]
There was No Added Value of Age-Adjusted D-Dimer Cut-Off to the YEARS Algorithm in Patients with Suspected Pulmonary Embolism
Prospective PEGeD Trial of Probability-Adjusted D-Dimer (NEJM, 2019) [MEDLINE]: n = 2017
Acute Pulmonary Embolism was Considered Ruled Out Without Further Testing in Outpatients with a Low Clinical Pretest Probability and a D-Dimer <1000 ng/mL or with a Moderate Clinical Pretest Probability and a D-Dimer <500 ng/mL
Overall, 7.4% of Patients Had Acute Pulmonary Embolism on Initial Diagnostic Testing
A Combination of a Low Clinical Pretest Probability and D-Dimer <1000 ng/mL Identified a Group of Patients at Low Risk for Pulmonary Embolism During Follow-Up
Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]
In Pregnant Women with Suspected Acute Pulmonary Embolism, D-Dimer Should Not Be Used to Exclude Acute Pulmonary Embolism (Weak Recommendation, Very Low Quality Evidence)
Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]
Plasma D-dimer Measurement (Preferably Using a High Sensitivity Assay, is Recommended in Outpatients/Emergency Department Patients with Low-Intermediate Clinical Probability, or those that are Acute Pulmonary Embolism-Unlikely, to Decrease the Need for Unnecessary Imaging and Irradiation (Class I, Level A)
As an Alternative to the Fixed D-Dimer Cutoff, a Negative D-Dimer Test Using an Age-Adjusted Cutoff (age x 10 mg/L, in Patients >50 y/o) Should Be Considered for Excluding Acute Pulmonary Embolism in Patients with Low-Intermediate Clinical Probability, or Those Who are Acute Pulmonary Embolism-Unlikely (Class IIa, Level B)
As an Alternative to the Fixed or Age-Adjusted D-Dimer Cutoff, D-Dimer Levels Adapted to Clinical Probability Should Be Considered to Exclude Acute Pulmonary Embolism (Class IIa, Level B)
D-Dimer Measurement is Not Recommended in Patients with High Clinical Probability, as a Normal Result Does Not Safely Exclude Acute Pulmonary Embolism, Even When Using a High Sensitivity Assay (Class III, Level A)
Allows for Evaluation of Superficial and Deep Venous Systems
Easily Repeated
Non-Invasive
Accuracy
Sensitivity: xxx
Specificity: xxx
Clinical Efficacy-Occlusiveness of Deep Venous Thrombosis
Study of Occlusiveness of Lower Extremity DVT in Patients After Hip Surgery (Thromb Haemost, 1996) [MEDLINE]
Most DVT’s Diagnosed in Asymptomatic Patients After Hip Surgery (59.1%-67.1%, Depending on the Vessel) are Non-Occlusive: for this reason, diagnostic methods based on venous flow measurements would be expected to be less sensitive
Systematic Review and Meta-Analysis of Risk Stratification of Patients with Acute PE Based on Presence/Absence of Lower Extremity DVT (Chest, 2016) [MEDLINE]
In Patients Diagnosed with Acute Symptomatic PE, Concomitant DVT was Significantly Associated with an Increased Risk of Death within 30 days of the PE Diagnosis, as Compared to Those without a Concomitant Lower Extremity DVT (6.2% vs 3.8%)
Clinical Efficacy-Other
Trial of Clinical Pretest Probability Scoring Combined with Lower Extremity Venous Ultrasound in the Diagnosis of Outpatient DVT (Lancet, 1997) [MEDLINE]
Using Pretest Probability Scoring with Lower Extremity Venous Ultrasound was Safe and Feasible
Prospective Study of Lower Extremity Venous Ultrasound in the Diagnosis of DVT (Ann Intern Med, 2004) [MEDLINE]
It is Safe to Withhold Anticoagulation After Negative Lower Extremity Doppler Studies in Nonpregnant Patients with a First Suspected Episode of Symptomatic Lower Extremity DVT
Systematic Review and Meta-Analysis of Risk Stratification of Patients with Acute PE Based on Presence/Absence of Lower Extremity DVT (Chest, 2016) [MEDLINE]
In Patients Diagnosed with Acute Symptomatic PE, Concomitant DVT was Significantly Associated with an Increased Risk of Death within 30 days of the PE Diagnosis, as Compared to Those without a Concomitant Lower Extremity DVT (6.2% vs 3.8%)
Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]
In Pregnant Women with Suspected Acute Pulmonary Embolism and Symptoms/Signs of Deep Venous Thrombosis, Bilateral Venous Compression Ultrasound of Lower Extremities is Recommended (Weak Recommendation, Very Low Quality Evidence)
If Positive, Anticoagulation Treatment is Recommended (Weak Recommendation, Very Low Quality Evidence)
If Negative, Further Testing is Recommended (Weak Recommendation, Very Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and No Symptoms/Signs of Deep Venous Thrombosis, Studies of the Pulmonary Vasculature are Recommended Rather than Venous Compression Ultrasound of the Lower Extremities (Weak Recommendation, Very Low Quality Evidence)
Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]
If a Compression Ultrasound Study Demonstrates a Proximal Deep Venous Thrombosis in a Patient with Clinical Suspicion of Acute Pulmonary Embolism, it is Recommended to Accept the Diagnosis of Venous Thromboembolism (and Acute Pulmonary Embolism) (Class I, Level A)
If Compression Ultrasound Study Demonstrates Only Distal Deep Venous Thrombosis, Further Testing Should Be Considered to Confirm Acute Pulmonary Embolism (Class IIa, Level B)
If a Positive Proximal Compression Ultrasound Study is Used to Confirm Acute Pulmonary Embolism, Assessment of Acute Pulmonary Embolism Severity Should Be Considered to Permit Risk-Adjusted Management (Class IIa, Level C)
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
CT Venogram is an Alternative to Compression Lower Extremity Venous Doppler Ultrasound for the Diagnosis of Lower Extremity Deep Venous Thrombosis When Ultrasound is Impractical (Patients with Lower Extremity Casting, Significant Lower Extremity Edema or Wounds, etc)
Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]
CT Venography is Not Recommended as an Adjunct to CT Pulmonary Artery Angiogram for the Diagnosis of Acute Pulmonary Embolism (Class III, Level B)
Recommendations for Diagnostic Testing Suspected Upper Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
If Upper Extremity Compression Venous Doppler Ultrasound is Negative with High Clinical Suspicion, Moderate/High-Sensitivity D-Dimer, Serial Ultrasound, CT Upper Extremity Venogram, or Gadolinium-Enhanced Magnetic Resonance Upper Extremity MRI Venogram is Recommended (Grade 2C Recommendation)
Gadolinium-Enhanced Magnetic Resonance Venogram and Pulmonary Artery Angiogram (MRA) (see Magnetic Resonance Imaging)
Advantages
No Exposure to Iodinated Radiographic Contrast
No Radiation Exposure
Disadvantages
Magnetic Resonance Venogram and Pulmonary Artery Angiogram Have High Rates of Technically Inadequate Studies [MEDLINE]: technically inadequate studies were found in 25% (range: 11-52%) of studies performed in the PIOPED III Study (2010), depending on the center
Due to the large number of technically inadequate studies in PIOPED III, magnetic resonance venography and pulmonary angiogram only identified 57% of patients with pulmonary embolism
Vascular opacification and motion artifact are the principal factors which influence interpretability of MRA [MEDLINE]: some centers appear to obtain better images (for unclear reasons)
Technically Adequate Magnetic Resonance Pulmonary Angiogram
Sensitivity: 78%
Specificity: 99%
Technically Adequate Magnetic Resonance Pulmonary Angiogram + Magnetic Resonance Venogram: combination has significantly higher sensitivity than magnetic resonance pulmonary angiogram alone (however, only 52% of patients had technically inadequate results)
Sensitivity: 92%
Specificity: 96%
Recommendations
Magnetic Resonance Pulmonary Artery Angiogram and Venogram Studies Should Only be Performed in Centers with Local Expertise
Recommendations (European Society of Cardiology and European Respiratory Society Guidelines for the Diagnosis and Management of Acute Pulmonary Embolism, 2019) (Eur Heart J, 2020) [MEDLINE]
Magnetic Resonance Pulmonary Artery Angiogram is Not Recommended to Rule Out Acute Pulmonary Embolism (Class III, Level A)
Recommendations for Diagnostic Testing Suspected Upper Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
If Upper Extremity Compression Venous Doppler Ultrasound is Negative with High Clinical Suspicion, Moderate/High-Sensitivity D-Dimer, Serial Ultrasound, CT Upper Extremity Venogram, or Gadolinium-Enhanced Magnetic Resonance Upper Extremity MRI Venogram is Recommended (Grade 2C Recommendation)
Lower Extremity Impedance Plethysmography (IPG)
Indications
Sensitive for Above the Knee Deep Venous Thrombosis
Lower Extremity Radiofibrinogen Study
Indications
Sensitive for Calf/Lower Thigh Deep Venous Thrombosis
Recommendations for Diagnostic Testing for Suspected Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Recommended Diagnostic Testing for Suspected First Lower Extremity Deep Venous Thrombosis if Risk Stratification is NOT USED to Classify Patient (By Pretest Probability)
Recommendations for Diagnostic Testing for Patients with No Risk Stratification with First Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Proximal or Whole Leg Lower Extremity Compression Venous Doppler Ultrasound is Recommended (Grade 1B Recommendation vs No Testing, Grade 2B vs D-Dimer Testing)
CT Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Not Recommended as the Routine Initial Diagnostic Test (Grade 1C Recommendation)
Gadolinium-Enhanced Magnetic Resonance Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Not Recommended as the Routine Initial Diagnostic Test (Grade 1C Recommendation)
Recommended Diagnostic Testing for Suspected First Lower Extremity Deep Venous Thrombosis if Risk Stratification is USED to Classify Patient (By Pretest Probability)
Recommendations for Diagnostic Testing for Patients with Low Pretest Probability of First Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]: one of the following
Moderate-Sensitivity D-Dimer (Grade 1B Recommendation): D-dimer is the preferred initial diagnostic test if there are no comorbid conditions which might be expected to elevate the D-dimer (Grade 2C Recommendation)
If D-Dimer is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
If D-Dimer is Positive, Compression Proximal Lower Extremity Venous Doppler Ultrasound is Recommended (Grade 2C Recommendation)
High-Sensitivity D-Dimer (Grade 1B Recommendation): D-dimer is the preferred initial diagnostic test if there are no comorbid conditions which might be expected to elevate the D-dimer (Grade 2C Recommendation)
If D-Dimer is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
If D-Dimer is Positive, Compression Proximal Lower Extremity Venous Doppler Ultrasound is Recommended (Grade 2C Recommendation)
Proximal Lower Extremity Compression Venous Doppler Ultrasound (Grade 1B Recommendation): ultrasound is the preferred initial diagnostic test if there are comorbid conditions which might be expected to elevate the D-dimer
If Proximal Ultrasound is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
CT Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Gadolinium-Enhanced Magnetic Resonance Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Recommendations for Diagnostic Testing for Patients with Moderate Pretest Probability of First Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]: one of the following
High-Sensitivity D-Dimer (Grade 1B Recommendation): high-sensitivity D-dimer is the preferred initial diagnostic test if there are no comorbid conditions which might be expected to elevate the D-dimer (Grade 2C Recommendation)
If D-Dimer is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
If D-Dimer is Positive, Proximal or Whole Leg Ultrasound is Recommended (Grade 1B Recommendation)
Proximal or Whole Leg Lower Extremity Compression Venous Doppler Ultrasound (Grade 1B Recommendation): ultrasound is the preferred initial diagnostic test if there are comorbid conditions which might be expected to elevate the D-dimer
If Proximal Ultrasound is Performed First and is Negative, Moderate/High-Sensitivity D-Dimer Immediately or Repeat Ultrasound in 7 Days is Recommended (Grade 1C Recommendation)
If Proximal Ultrasound is Negative, But D-Dimer is Positive, Repeat Ultrasound in 7 Days is Recommended (Grade 1B Recommendation)
If Whole Leg Ultrasound is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
If Isolated Distal DVT is Detected, Serial Lower Extremity Ultrasound to Rule Out Proximal Extension is Recommended (Grade 2C Recommendation): patients with severe symptoms and risk factors for extension are more likely to benefit from treatment over repeat ultrasound (see treatment below)
CT Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Gadolinium-Enhanced Magnetic Resonance Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Recommendations for Diagnostic Testing for Patients with High Pretest Probability of First Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Moderate/High-Sensitivity D-Dimer Should Not Be Used as Standalone Tests in Patients with High Pretest Probability of DVT (Grade 1B Recommendation)
Proximal or Whole Leg Lower Extremity Compression Venous Doppler Ultrasound is Recommended (Grade 1B Recommendation)
Whole Leg Ultrasound is Preferred Over Proximal Ultrasound in Patients Who are Unable to Return for Serial Lower Extremity Ultrasound Testing and Those with Severe Symptoms Consistent with Distal DVT
CT Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
Gadolinium-Enhanced Magnetic Resonance Lower Extremity Venogram: may be alternatively used when lower extremity venous ultrasound is not practical or possible
If Proximal Lower Extremity Compression Venous Doppler Ultrasound is Negative, Repeat Proximal/Whole Leg Lower Extremity Compression Venous Doppler Ultrasound or High Sensitivity D-Dimer in 7 Days is Recommended (Grade 1B Recommendation)
If Proximal Lower Extremity Compression Venous Doppler Ultrasound is Negative, But D-Dimer is Positive, Repeat Proximal/Whole Leg Lower Extremity Compression Venous Doppler Ultrasound in 7 Days is Recommended (Grade 1B Recommendation)
If Whole Leg Lower Extremity Compression Venous Doppler Ultrasound is Negative, No Further Testing is Recommended (Grade 1B Recommendation)
If Unexplained Lower Extremity Swelling is Present with Negative Lower Extremity Ultrasound and Negative/Positive D-Dimer, Iliac Veins Should Be imaged to Exclude Isolated Iliac Vein DVT
Recommended Diagnostic Testing for Suspected Recurrent Lower Extremity Deep Venous Thrombosis
Recommendations for Diagnostic Testing for Patients with Recurrent Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Proximal Lower Extremity Compression Venous Doppler Ultrasound or High-Sensitivity D-Dimer is Recommended (Grade 1B Recommendation)
If High-Sensitivity D-Dimer is Positive, Proximal Lower Extremity Compression Venous Doppler Ultrasound is Recommended (Grade 1B Recommendation)
If Proximal Lower Extremity Compression Venous Doppler Ultrasound is Negative, Repeat Proximal Lower Extremity Compression Venous Doppler Ultrasound or High-Sensitivity D-Dimer in 7 Days is Recommended (Grade 1B Recommendation)
Recommended Diagnostic Testing for Suspected Pregnancy-Associated Lower Extremity Deep Venous Thrombosis
Recommendations for Diagnostic Testing for Pregnant Patients with Suspected Lower Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
If Proximal Lower Extremity Compression Venous Doppler Ultrasound is Negative, Repeat Proximal Lower Extremity Compression Venous Doppler Ultrasound in 3 and 7 Days (Grade 1B Recommendation) or Sensitive D-Dimer at Time of Presentation (Grade 2B Recommendation) is Recommended
If Isolated Iliac Vein DVT is Suspected, But Proximal Lower Extremity Compression Venous Doppler Ultrasound is Negative, Ultrasound of Iliac Vein (Grade 2C Recommendation), Venography (Grade 2C Recommendation), or Direct MRI (Grade 2C Recommendation) is Recommended
Recommendations for Diagnostic Testing for Suspected Upper Extremity Deep Venous Thrombosis
Recommendations for Diagnostic Testing Suspected Upper Extremity Deep Venous Thrombosis (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
If Upper Extremity Compression Venous Doppler Ultrasound is Negative with High Clinical Suspicion, Moderate/High-Sensitivity D-Dimer, Serial Ultrasound, CT Upper Extremity Venogram, or Gadolinium-Enhanced Magnetic Resonance Upper Extremity MRI Venogram is Recommended (Grade 2C Recommendation)
Clinical Use of Diagnostic Algorithms in Upper Extremity Deep Venous Thrombosis
Use of Diagnostic Algorithm for Upper Extremity DVT (2014) [MEDLINE]
Study: multi-center international study (n = 406 inpatients) in Europe/US using algorithm with sequential application of a clinical decision score, D-dimer testing, and ultrasonography
Main Findings: combination of a clinical decision score, D-dimer testing, and ultrasonography can safely and effectively exclude the diagnosis of upper extremity DVT
Clinical Evaluation for Suspected Pulmonary Embolism in Pregnancy (see Pregnancy)
Clinical Efficacy
Markov Decision Model Study of Six International Societal Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy (Chest, 2022) [MEDLINE]
Base-Case Analysis Demonstrated that the American Thoracic Society/Society of Thoracic Radiology (ATS-STR) Guidelines Yielded the Highest Health Benefits (22.90 QALYs) and was Cost-Effective (ICER of $7,808) Over the Australian Society of Thrombosis and Haemostasis Guidelines and the Society of Obstetric Medicine of Australia and New Zealand (ASTH-SOMANZ) Guidelines
Recommendations (American Thoracic Society/Society of Thoracic Radiology Clinical Practice Guidelines for the Evaluation of Suspected Pulmonary Embolism in Pregnancy) (Am J Respir Crit Care Med, 2011) [MEDLINE]
In Pregnant Women with Suspected Acute Pulmonary Embolism, D-Dimer Should Not Be Used to Exclude Acute Pulmonary Embolism (Weak Recommendation, Very Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and Symptoms/Signs of Deep Venous Thrombosis, Bilateral Venous Compression Ultrasound of Lower Extremities is Recommended (Weak Recommendation, Very Low Quality Evidence)
If Positive, Anticoagulation Treatment is Recommended (Weak Recommendation, Very Low Quality Evidence)
If Negative, Further Testing is Recommended (Weak Recommendation, Very Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and No Symptoms/Signs of Deep Venous Thrombosis, Studies of the Pulmonary Vasculature are Recommended Rather than Venous Compression Ultrasound of the Lower Extremities (Weak Recommendation, Very Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism, Chest X-Ray is Recommended as the First Radiation-Associated Procedure in the Imaging Work-Up (Strong Recommendation, Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and a Normal Chest X-Ray, V/Q Scan is Recommended as the Next Imaging Test Rather than CT Pulmonary Artery Angiogram (Strong Recommendation, Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and a Non-Diagnostic V/Q Scan, Further Diagnostic Testing is Recommended Over Clinical Management Alone (Weak Recommendation, Low Quality Evidence)
In Patients with a Non-Diagnostic V/Q Scan in Whom a Decision is Made to Further Investigate, CT Pulmonary Artery Angiogram is Recommended Over Digital Subtraction Angiography (Strong Recommendation, Very Low Quality Evidence)
In Pregnant Women with Suspected Acute Pulmonary Embolism and an Abnormal Chest X-Ray, CT Pulmonary Artery Angiogram is Suggested as the Next Imaging Test Rather than V/Q Scan (Weak Recommendation, Very Low Quality Evidence)
Clinical Manifestations of Lower Extremity Deep Venous Thrombosis
General Comments
Anatomic Site of Deep Venous Thrombosis (DVT)
Proximal Deep Venous Thrombosis (DVT)
Femoral Veins
Iliac Veins
Popliteal Veins
Distal (Calf) Deep Venous Thrombosis (DVT)
Crural Calf Veins
Anterior Tibial Veins
Posterior Tibial Veins
Peroneal Veins
Muscular Calf Veins
Gastrocnemius Veins
Soleal Veins
Other Muscular Calf Veins
Provoked vs Unprovoked Deep Venous Thrombosis (DVT)
Provoked Deep Venous Thrombosis: deep venous thrombosis attributable to an identifiable etiology or provoking event
Unprovoked Deep Venous Thrombosis: deep venous thrombosis with no identifiable etiology or provoking event
Symptomatic vs Asymptomatic Deep Venous Thrombosis (DVT)
Asymptomatic Deep Venous Thrombosis: DVT diagnosed with a lack of clinical symptoms (ie incidentally diagnosed on radiologic study performed in an asymptomatic patient)
Symptomatic Deep Venous Thrombosis: presence of clinical symptoms that would lead to the radiologic diagnosis of DVT
Norwegian Tromso Study of the Association Between Venous Thromboembolism and Atrial Fibrillation (J Am Heart Assoc, 2014) [MEDLINE]
Venous Thromboembolism was Associated with an Increased Future Risk of Atrial Fibrillation: 9.3% of patients with venous thromboembolism developed subsequent atrial fibrillation
Risk of Atrial Fibrillation was Particularly High in the First 6 Months After the Venous Thomboembolism Event (Hazard Ratio 4.00, 95% CI: 2.21-7.25) and in Those with Pulmonary Embolism (Hazard Ratio 1.78, 95% CI: 1.13-2.8)
Peripheral Edema (Particularly Unilateral) is Common
Free-Floating Deep Venous Thrombosis
Clinical Data
Study of Clinical Significance of Free-Floating Thrombus (J Vasc Surg, 1990) [MEDLINE]
Free-Floating Thrombus Occurred in 10% of Cases of Acute Deep Venous Thrombosis
Only 13% of Free-Floating Thrombi were Associated with Clinically Significant Pulmonary Embolism (by Ventilation-Perfusion Scanning)
When Followed by Serial Lower Extremity Dopplers, Most Free-Floating Thrombi Do Not Embolize, But Rather They Become Attached to the Vein Wall or Resolve
French Prospective Trial Examining the Impact of Detecting Free-Floating Thrombus (on Lower Extremity Doppler Ultrasound) in Deep Venous Thrombosis (Arch Intern Med, 1997) [MEDLINE]
Doppler Ultrasound Had a Sensitivity of 68% and a Specificity of 86% for the Diagnosis of Free-Floating Thrombus on Doppler Ultrasound
In the Setting of Appropriate Anticoagulation Therapy (Almost All of the Subjects Received the Low Molecular Weight Heparin, Nadroparin, and Only One Subject Received Unfractionated Heparin Drip), the Presence of Free-Floating Thrombus on a Lower Extremity Doppler Study Did Not Increase the Risk of Acute Pulmonary Embolism (At Day 10, the Incidence of Pulmonary Embolism was 3% in Free-Floating Group vs 4% in the Occlusive Group; p = 0.92)
Importantly, the Trial was Performed in 1992-1993 (Using Only Unfractionated Heparin and Low Molecular Weight Heparin) and the Results Cannot Be Applied to Patients Who Receive Direct Oral Anticoagulants (DOAC’s), Which Were Not Available for Use at That Time
Study of Data from the RIETE Registry of Symptomatic Deep Venous Thrombosis Cases (J Thromb Thrombolysis, 2011) [MEDLINE]: n = 14,480
Fever was Present (at Presentation) in 4.9% of Symptomatic Deep Venous Thrombosis Cases
Patients Initially Presenting with Fever Had a Higher Mortality Rate, as Compared to Those without Fever (5.8% vs 2.9%; Odds Ratio 2.6; 95% CI: 1.9-3.5)
Among the Causes of Death, Pulmonary Embolism (0.7% vs 0.1%) and Infection (1.1% vs 0.3%) were Significantly More Common in Symptomatic Deep Venous Thrombosis Patients Presenting with Fever
Multivariate Analysis Confirmed that Deep Venous Thrombosis Patients with Fever Had an Increased Mortality (Hazard Ratio 2.00; 95% CI: 1.44-2.77), Irrespective of the Patient Age, Body Weight, and Risk Factors for Venous Thromboembolism
Clinical Manifestations of Upper Extremity Deep Venous Thrombosis
Sequential Compression Devices (SCD’s) Have Not Been Rigorously Evaluated in Critically Ill Patient Populations (Ann Surg, 2010) [MEDLINE]
Clinical Efficacy-General
Randomized EXCLAIM Trial of Extended-Duration Enoxaparin (28 +/- 4 Days, After Receiving Open Label Enoxaparin for an Initial 10 +/4 Days) in Acutely Ill Medical Patients with Decreased Mobility (Ann Intern Med, 2010) [MEDLINE]
Extended-Duration Enoxaparin Decreases Venous Thromboembolism More than it Increases Major Bleeding Events in Acutely Ill Medical Patients with Level 1 Immobility, Tose >75 y/o, and Women
International Economic Evaluation of Pharmacologic Deep Venous Thrombosis Prophylaxis vs Weekly Ultrasound Screening in Intensive Care Unit Patients in Canada/US/Australia (Am J Resp Crit Care Med, 2011) [MEDLINE]
Study Used Markov Decision Analysis Comparing Weekly Ultrasound Screening (Case Finding) to Pharmacologic Prophylaxis (Limitation: There are No Randomized Trials Examining Screening for Deep Venous Thrombosis in Critically Ill Patients)
In ICU Patients Who Received Standard Deep Venous Thrombosis Prophylaxis, Weekly Doppler Compression Ultrasound Screening Cost >$200k/QALY (At >50-$100k/QALY, This is Not Considered Cost-Effective)
Although Increased Venous Thromboembolism Detection was Noted, Screening was Associated with More Bleeding Events (Due to a Greater Frequency of Anticoagulation and Higher Number of False-Positive Studies for Deep Venous Thrombosis)
Very Small Improvements in Quality-Adjusted Survival Did Not Justify the Additional Costs of Routine Weekly Screening
Appropriate Pharmacologic Prophylaxis Combined with Deep Venous Thrombosis Case Finding was at Least as Effective, Less Time-Consuming, and Less Expensive than Routine Weekly Ultrasound Screening
Agrees with Prior Study Which Failed to Demonstrate Benefit of Routine Ultrasound Deep Venous Thrombosis Screening in Critically Ill Patients (Although Weekly Ultrasound Screening was Found Effective in Subset with Femoral Central Venous Catheters) (Am J Resp Crit Care Med, 2003) [MEDLINE]
However, when the Risk of Proximal Deep Venous Thrombosis During Critical Illness was ≥16%, Ultrasound Screening Cost <$50k/QALY and was Cost-Effective
In Patients with Multiple Trauma, Acute Brain/Spinal Cord Injury, Cancer, and in Critically Ill Patients Who Do Not Receive Pharmacologic Prophylaxis, the Risk of Deep Venous Thrombosis May Approach the 16% Level (Arch Intern Med, 2001) [MEDLINE]
In a Study of Critically Injured Trauma Patients Who Did Not Receive Pharmacologic Prophylaxis, the Risk of Proximal DVT was 18% (NEJM, 1994) [MEDLINE]
Therefore, in Intensive Care Unit Patients, Pharmacologic Deep Venous Thrombosis Prophylaxis Should Be Provided (if Possible)
However, in Select High-Risk Patient Populations (as Noted Above), Weekly Ultrasound Screening May Be Cost-Effective
LIFENOX Trial of Enoxaparin with Elastic Graduated Compression Stockings vs Elastic Graduated Compression Stockings Alone in Hospitalized Acutely Ill Medical Patients (NEJM, 2011) [MEDLINE]: RCT (n = 8307)
In Hospitalized Acutely Ill Medical Patients, Enoxaparin Plus Elastic Graduated Compression Stockings, as Compared with Elastic Graduated Compression Stockings Alone, was Not Associated with Decreased All-Cause Mortality Rate
PROTECT Trial of Dalteparin vs Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (NEJM, 2011) [MEDLINE]: n = 1873
Dalteparin was Not Superior to Unfractionated Heparin Deep Venous Thrombosis Prophylaxis, in Terms of Incidence of Proximal Deep Venous Thrombosis
Economic Evaluation of Data Derived from the PROTECT Trial (JAMA, 2014) [MEDLINE]: n = 2,344 (23 centers in 5 countries)
In Critically Ill Medical-Surgical Patients Undergoing Pharmacologic Deep Venous Thrombosis Prophylaxis, Dalteparin Had a Lower Acute Pulmonary Embolism Rate, Lower Heparin-Induced Thrombocytopenia (HIT) Rate, and Similar or Lower Cost, as Compared to Unfractionated Heparin Deep Venous Thrombosis Prophylaxis
Systematic Review and Network Meta-Analysis of Deep Venous Thrombosis Prophylaxis in Acutely Ill Hospitalized Inpatients (BMJ, 2022) [MEDLINE]: n = 90,095 (44 randomized controlled trials)
Evidence of Low-Moderate Quality Indicated that None of the Interventions Decreased All-Cause Mortality, as Compared to Placebo
Low-Molecular Weight Heparin in an Intermediate Dose Conferred the Best Balance of Benefits/Harms for Prevention of Venous Thromboembolism
Unfractionated Heparin (in Particular the Intermediate Dose) and Direct Oral Anticoagulants Had the Least Favorable Profile
Main Limitations of This Study Include the Quality of Evidence (Which was Generally Low-Moderate Due to Imprecision and Within-Study Bias) and Statistical Inconsistency
Clinical Efficacy-Deep Venous Thrombosis Prophylaxis in the Setting of Critical Illness
Systematic Review and Meta-Analysis of Venous Thromboembolism Prophylaxis in Critically Ill Adults (Chest, 2022) [MEDLINE]: n = 9,619 (from 13 randomized controlled trials)
Low Molecular Weight Heparin Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.59; 95% Credible Interval: 0.33-0.90; High Certainty), as Compared to Control (Either No Prophylaxis, Placebo, or Compression Stockings Only)
Unfractionated Heparin May Have Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.82; 95% Credible Interval: 0.47-1.37; Low Certainty), as Compared to Control
Mechanical Compressive Devices May Have Decreased the Incidence of Deep Venous Thrombosis (Odds Ratio 0.85; Credible Interval: 0.50-1.50; Low Certainty), as Compared to Control
Low Molecular Weight Heparin was Probably More Effective than Unfractionated Heparin in Decreasing the Incidence of Deep Venous Thrombosis (Odds Ratio 0.72 [95% Credible Interval: 0.46-0.98; Moderate Certainty)
Low Molecular Weight Heparin Should Be Considered the Primary Pharmacologic Agent for Thromboprophylaxis
Combination Pharmacologic Therapy and Mechanical Compressive Devices Demonstrated an Unclear Effect on the Incidence of Deep Venous Thrombosis, as Compared with Either Therapy Alone (Very Low Certainty)
Clinical Efficacy-Deep Venous Thrombosis Prophylaxis in the Setting of Low Body Weight and Obesity
Study of High-Dose Heparin Deep Venous Thrombosis Prophylaxis in Hospitalized Morbidly Obese Patients (>100 kg and BMI ≥40) (Thromb Haemost, 2014) [MEDLINE]: n = 3,928
High-Dose Heparin Deep Venous Thrombosis (Unfractionated Heparin 7500 U TID or Enoxaparin 40 mg BID) Halved the Odds of Symptomatic Venous Thromboembolism (0.77%), as Compared to Standard Dose Heparin Deep Venous Thrombosis (Unfractionated Heparin 5000 U BID/TID or Enoxaparin 40 mg qday) (1.48%) (Odds Ratio 0.52; 95% Confidence Interval: 0.27-1.00; p = 0.050)
Bleeding Rates were Similar in Both Groups
Retrospective Study of High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis in Overweight Neurocritical Care Patients (>100 kg) (J Thromb Thrombolysis, 2015) [MEDLINE]
High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis Group (7500 U q8hrs) and Standard Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis Group (5000 U q8hrs) Had Similar Venous Thromboembolism Rates
Both Groups Had Similar Rates of Bleeding Complications
Single-Center Retrospective Studies of DVT Prophylaxis in Hospitalized Overweight/Obese Patients (>100 kg) (Pharmacotherapy, 2016) [MEDLINE]: n = 1,335
High-Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (7500 U q8hrs), as Compared to Standard Dose Unfractionated Heparin Deep Venous Thrombosis Prophylaxis (5000 U q8hrs) Had Similar Venous Thromboembolism Rates for All BMI Classes (BMI 25-29.9 kg/m2, BMI 30-34.9 kg/m2, BMI 35-39.9 kg/m2, and BMI ≥ 40 kg/m2)
Bleeding Rate was Higher in the High-Dose Group
Literature Review of Enoxaparin Dosing for Patients at Extremes of Weight (Ann Pharmacother, 2018) [MEDLINE]
Low Body Weight Patients May Benefit from Enoxaparin 30 mg SQ qday for Venous Thromboembolism Prophylaxis, and Standard Weight-Based Dosing for Venous Thromboembolism Treatment
In Patients with BMI ≥40 kg/m2, Enoxaparin 40 mg SQ BID is Recommended for Venous Thromboembolism Prophylaxis
In Patients with BMI ≥50 kg/m2, Consideration Should Be Given for Higher Doses for Venous Thromboembolism Prophylaxis
Clinical Efficacy-Apixaban (Eliquis) (see Apixaban)
ADOPT Trial Examining Prolonged Apixaban (For 30 Days) vs Enoxaparin (For ≥6 Days) for Deep Venous Thrombosis Prophylaxis After Hospital Discharge in Medical Patients (NEJM, 2011) [MEDLINE]: double-blind, double-dummy, placebo-controlled trial (n = 6528)
In Medically Ill Patients, an Extended Course of Apixaban Deep Venous Thrombosis Prophylaxis was not Superior to a Shorter Course with Enoxaparin
Apixaban was Associated with Significantly More Major Bleeding Events (0.47%) than Enoxaparin (0.19%) at Day 30
APEX Trial of Extended-Duration Betrixaban (35-42 Days) After Initial Enoxaparin (x 10 +/- 4 Days) for DVT Prophylaxis in Hospitalized, Acutely Ill Medical Patients (Am Heart J, 2017) [MEDLINE]: randomized, double-blind, double-dummy, active-controlled, multi-national
Betrixaban (Only at the Higher Dose of 80 mg) + Initial Enoxaparin (x 10 +/- 4 Days) was Superior to Initial Enoxaparin Alone (x 10 +/- 4 Days), in Terms of Venous Thromboembolism at Day 42, without an Increased Risk of Bleeding
Clinical Efficacy-Rivaroxaban (Xarelto) (see Rivaroxaban)
MAGELLAN Non-Inferiority Trial Comparing Rivaroxaban (x 35 +/- 4 Days) to Enoxaparin (x 10 +/- 4 Days) for DVT Prophylaxis in Acutely Ill Medical Patients (NEJM, 2013) [MEDLINE]: multi-center, randomized ( n = 8101)
At Day 10: Rivaroxaban was Equivalent (2.7%) to Enoxaparin (2.7%), in Terms of Venous Thromboembolism
At Day 35: Rivaroxaban was Superior (4.4%) to Enoxaparin (5.7%), in Terms of Venous Thromboembolism
At Day 10: Rivaroxaban Had Significantly Higher Bleeding Risk (2.8%) vs Enoxaparin (1.2%)
At Day 35: Rivaroxaban Had Significantly Higher Bleeding Risk (4.1%) vs Enoxaparin (1.7%)
MARINER Trial of Prophylactic Rivaroxaban Begun and Continuing After Hospital Discharge (x 45 Days) in High-Risk Medical Patients (Thromb Haemost, 2016) [MEDLINE]: randomized, double-blind, placebo-controlled
In Process: endpoints of symptomatic VTE and VTE-related death
Clinical Efficacy-Use of Sequential Compression Devices (SCD’s) in Addition to Pharmacologic Deep Venous Thrombosis Prophylaxis (see Sequential Compression Device)
Systematic Review and Meta-Analysis of the Use of Sequential Compression Devices (SCD’s) in Addition to Pharmacologic Deep Venous Thrombosis Prophylaxis in Hospitalized Adults (Crit Care Explor, 2022) [MEDLINE]: n = 8,796 (17 trials)
Intermittent Pneumatic Compression Device was Mostly Applied Tp to the Thigh and Pharmacological Thromboprophylaxis Consisted of Primarily Low-Molecular-Weight Heparin
Adjunctive Intermittent Pneumatic Compression was Associated with a Decreased Risk of Venous Thromboembolism (15 Trials, RR = 0.53; 95% CI: 0.35-0.81]) and Deep Venous Thrmbosis (14 Trials, RR = 0.52; 95% CI: 0.33-0.81), But Not Pulmonary Embolism (7 Trials, RR = 0.73; 95% CI: 0.32-1.68)
The Quality of Evidence was Graded as Low, Downgraded by Risk of Bias and Inconsistency
Moderate and Very Low Quality Evidence Respectively, Suggests that Adjunctive Intermittent Pneumatic Compression is Unlikely to Change the Risk of All-Cause Mortality or Adverse Events
Subgroup Analyses Indicate a More Evident Apparent Benefit in Industry-Funded Trials
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Asymptomatic Hypercoagulable State
Mechanical/Pharmacologic Prophylaxis is Not Recommended (Grade 1C Recommendation)
Chronically Immobilized Patients
Pharmacologic Prophylaxis is Not Recommended (Grade 2C Recommendation)
Critically Ill Patients
For Critically Ill Patients Routine Ultrasound Screening for Deep Venous Thrombosis is Not Recommended (Grade 2B Recommendation)
Low Molecular Weight Heparin or Low Dose Unfractionated Heparin Prophylaxis is Recommended (Grade 2C Recommendation)
For Critically Ill Patients with High Risk for Major Hemorrhage, Graduated Compression Stockings/Sequential Compression Devices are Recommended Until Bleeding Risk Decreases (at Which Time Pharmacologic Prophylaxis Should Be Substituted for Mechanical Prophylaxis) (Grade 2C Recommendation)
Hospitalized Acutely Ill Medical Patients
Hospitalized Acutely Ill Medical Patients with High Risk of Thrombosis, Low Molecular Weight Heparin, Low Dose Unfractionated Heparin Prophylaxis BID/TID, or Fondaparinux is Recommended (Grade 1B Recommendation)
For Hospitalized Acutely Ill Medical Patients with High Risk of Thrombosis and High Risk for Major Hemorrhage, Graduated Compression Stockings/Sequential Compression Devices are Recommended Until Bleeding Risk Decreases (at Which Time Pharmacologic Prophylaxis Should Be Substituted for Mechanical Prophylaxis) (Grade 2C Recommendation)
Hospitalized Acutely Ill Medical Patients with Low Risk of Thrombosis, No Pharmacologic or Mechanical Prophylaxis is Recommended
For Hospitalized Acutely Ill Medical Patients Who Receive an Initial Course of Prophylaxis, Extension of Duration Beyond the Period of Patient Immobilization or the Acute Hospital Stay is Not Recommended (Grade 2B Recommendation)
Persons Traveling Long Distance with Increased Risk of Venous Thrombembolism (Active Malignancy, Advanced Age, Estrogen Use, Known Hypercoagulable State, Limited Mobility, Pregnancy, Previous Venous Thromboembolism, Recent Surgery/Trauma, Severe Obesity)
Graduated Venous Compression Stockings (with 15-30 mm Hg of Pressure at the Ankle) are Recommended (Grade 2C Recommendation)
Other Recommendations
Deep Venous Thrombosis Prophylaxis in the Setting of Obesity
High Venous Thromboembolism-Risk Bariatric Surgery with BMI ≤50 kg/m2: enoxaparin 40 mg q12hrs
High Venous Thromboembolism-Risk Bariatric Surgery with BMI >50 kg/m2: enoxaparin 60 mg q12hrs
Abdominal-Pelvic Surgery Patients
Clinical Efficacy
Systematic Review of Risk of Heparin-Induced Thrombocytopenia in Post-Operative Patients Comparing Unfractionated Heparin vs Low Molecular Weight Heparin DVT Prophlaxis (Cochrane Database Syst Rev, 2012) [MEDLINE]
Lower incidence of HIT and HIT Complicated by Venous Thromboembolism in Postoperative Patients Undergoing Low Molecular Weight Heparin DVT Prophylaxis, as Compared to Unfractionated Heparin DVT Prophylaxis
Economic Evaluation Data Derived from PROTECT Trial (JAMA, 2014) [MEDLINE]: economic evaluation of dalteparin vs unfractionated heparin prophylaxis in medical and surgical critically ill patients (n = 2344 in 23 centers in 5 countries)
In Critically Ill Medical-Surgical Patients Undergoing Pharmacologic DVT Prophylaxis, Dalteparin Exhibited a Lower PE Rate, Lower Heparin-Induced Thromobcytopenia (HIT) Rate, and Similar or Lower Cost, as Compared to Unfractionated Heparin DVT Prophylaxis
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Cardiac Surgery with Uncomplicated Post-Operative Course: mechanical prophylaxis (preferably sequential compression devices) is recommended (Grade 2C Recommendation)
Cardiac Surgery with Hospital Course Complicated by One or More Non-Hemorrhagic Surgical Complications: mechanical prophylaxis (preferably sequential compression devices) AND either low-dose unfractionated heparin or low molecular weight heparin prophylaxis is recommended (Grade 2C Recommendation)
Thoracic Surgery Patients
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Thoracic Surgery with Moderate Risk of Venous Thromboembolism (Without Risk for Post-Operative Hemorrhage): sequential compression devices (Grade 2C Recommendation), low-dose unfractionated heparin (Grade 2B Recommendation), or low molecular weight heparin prophylaxis (Grade 2B Recommendation) is recommended
Craniotomy Patients
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Craniotomy with Very High Risk for Venous Thromboembolism (Craniotomy Performed for Malignant Disease): mechanical prophylaxis (preferably sequential compression devices) is recommended with addition of pharmacologic prophylaxis once hemostasis is established and the risk of bleeding decreases (Grade 2C Recommendation)
Spinal Surgery Patients
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Spinal Surgery with Very High Risk for Venous Thromboembolism (Spinal Surgery Performed for Malignant Disease or Surgery with Combined Anterior-Posterior Approach): mechanical prophylaxis (preferably sequential compression devices) is recommended with addition of pharmacologic prophylaxis once hemostasis is established and the risk of bleeding decreases (Grade 2C Recommendation)
Major Trauma Patients (Traumatic Brain Injury, Traumatic Spinal Injury, Spine Surgery for Trauma)
Clinical Efficacy
Cost-Effectiveness Retrospective Analysis of DVT Surveillance in Trauma Patients (n = 4234) in the ICU (PLoS One, 2014) [MEDLINE]
Ultrasound Screening of Trauma Patients is Cost-Effective: cost is $29,102/QALY
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Major Trauma: sequential compression devices (Grade 2C Recommendation), low-dose unfractionated heparin (Grade 2C Recommendation), or low molecular weight heparin prophylaxis (Grade 2C Recommendation) is recommended
Major Trauma with Very High Risk for Venous Thromboembolism: mechanical prophylaxis (preferably sequential compression devices) should be added to pharmacologic prophylaxis if not contraindicated by lower extremity injury (Grade 2C Recommendation)
Major Trauma with Contraindications to Low-Dose Unfractionated Heparin/Low Molecular Weight Heparin: mechanical prophylaxis (preferably sequential compression devices) is recommended (when not contraindicated by presence of lower extremity injury) (Grade 2C Recommendation), with addition of low-dose unfractionated heparin/low molecular weight heparin when bleeding risk decreases or contraindication heparin resolves (Grade 2C)
IVC Filter Placement as Primary Prevention of Venous Thromboembolism in Major Trauma: not recommended (Grade 2C Recommendation)
Screening Lower Extremity Doppler Ultrasound in Major Trauma: not recommended (Grade 2C Recommendation)
Orthopedic Surgery Patients (Total Hip Arthroplasty, Total Knee Arthroplasty, Hip Fracture Surgery)
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
Type of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty: one of the following is recommended for a minimum of 10-14 days
Apixaban (Eliquis) (see Apixaban) (Grade 1B Recommendation)
Dabigatran (Pradaxa) (see Dabigatran) (Grade 1B Recommendation)
Low Molecular Weight Heparin (Grade 1B Recommendation): low molecular weight heparin (if started pre-operatively, started 12 hrs before surgery) is suggested as the preferred agent for DVT prophylaxis (in terms of bleeding risk, efficacy, and long-term safety data) for total hip arthroplasty/total knee arthroplasty (Grade 2C Recommendation vs apixaban/dabigatran/fondaparinux/low-dose unfractionated heparin/rivaroxaban; Grade 2C Recommendation vs aspirin/coumadin)
Fondaparinux (Arixtra) (see Fondaparinux) (Grade 1B Recommendation)
Low-Dose Unfractionated Heparin Prophylaxis (see Heparin) (Grade 1B Recommendation)
Rivaroxaban (Xarelto) (see Rivaroxaban) (Grade 1B Recommendation)
Sequential Compression Device (SCD) (see Sequential Compression Device) (Grade 1C Recommendation): suggested to be used alone if bleeding risk contraindicates use of an antithrombotic agent (Grade 2C Recommendation)
Type of DVT Prophylaxis Hip Fracture Surgery: one of the following is recommended for 10-14 days
Low Molecular Weight Heparin (Grade 1B Recommendation): low molecular weight heparin (if started pre-operatively, started at least 12 hrs before surgery) is suggested as the preferred agent for DVT prophylaxis (in terms of bleeding risk, efficacy, and long-term safety data) for hip fracture surgery (Grade 2C Recommendation vs fondaparinux/low-dose unfractionated heparin; Grade 2C Recommendation vs aspirin/coumadin)
Fondaparinux (Arixtra) (see Fondaparinux) (Grade 1B Recommendation)
Low-Dose Unfractionated Heparin Prophylaxis (see Heparin) (Grade 1B Recommendation)
Sequential Compression Device (SCD) (see Sequential Compression Device) (Grade 1C Recommendation): suggested to be used alone if bleeding risk contraindicates use of an antithrombotic agent (Grade 2C Recommendation)
Dual DVT Prophylaxis with Antithrombotic Agent and Sequential Compression Device for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery During the Hospital Stay: recommended (Grade 2C Recommendation)
Timing of Initiation of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: starting DVT prophylaxis at least 12 hrs pre-operatively or 12 or more hrs post-operatively is recommended (Grade 1B Recommendation)
Duration of DVT Prophylaxis for Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: duration of prophylaxis in the outpatient period for up to 35 days from the date of surgery is suggested (Grade 2B Recommendation)
IVC Filter Placement as Primary Prevention of Venous Thromboembolism in Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery: not recommended (Grade 2C Recommendation)
Screening Lower Extremity Doppler Ultrasound in Asymptomatic Total Hip Arthroplasty/Total Knee Arthroplasty and Hip Fracture Surgery Prior to Hospital Discharge: not recommended (Grade 1B Recommendation)
Isolated Lower Leg Injury (Distal to Knee) Patients
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Isolated Lower Leg Injury Requiring Immobilization: no prophylaxis is recommended (Grade 2C Recommendation)
Knee Arthroscopy Patients
Recommendations (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) (Chest, 2012) [MEDLINE]
Knee Arthroscopy without Prior History of Venous Thromboembolism: no prophylaxis is recommended (Grade 2B Recommendation)
References
American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2012
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American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2016
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European Society of Cardiology/European Respiratory Society Clinical Practice Guidelines 2019
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PERT Consortium Clinical Practice Guidelines 2019
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American Society of Hematology Clinical Practice Guidelines 2020
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American College of Chest Physicians Evidence-Based Clinical Practice Guidelines 2021
Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report. Chest. 2021 Dec;160(6):e545-e608. doi: 10.1016/j.chest.2021.07.055 [MEDLINE]
General
Anticoagulant drugs in the treatment of pulmonary embolism. A controlled trial. Lancet. 1960 Jun 18;1(7138):1309-12 [MEDLINE]
Source of non-lethal pulmonary emboli. Lancet. 1974 Feb 16;1(7851):258-9 [MEDLINE]
A prospective study of venous thromboembolism after major trauma. N Engl J Med 1994; 331:1601–1606 [MEDLINE]
A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Prévention du Risque d’Embolie Pulmonaire par Interruption Cave Study Group. N Engl J Med. 1998;338(7):409 [MEDLINE]
Vena caval filters: a comprehensive review. Blood. 2000;95(12):3669 [MEDLINE]
Predictors of rehospitalization for symptomatic venous thromboembolism after total hip arthroplasty. N Engl J Med. 2000;343(24):1758 [MEDLINE]
Extended-duration prophylaxis against venous thromboembolism after total hip or knee replacement: a meta-analysis of the randomised trials. Lancet. 2001;358(9275):9 [MEDLINE]
Deep vein thrombosis and its prevention in critically ill adults. Arch Intern Med 2001;161:1268–1279 [MEDLINE]
Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med. 2003;163(14):1711 [MEDLINE]
Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005; 172:1041-1046 [MEDLINE]
Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med. 2005 Jul;33(7):1565-71 [MEDLINE]
Effectiveness of managing suspected pulmonary embolism using an algorithm combining clinical probability, D-dimer testing, and computed tomography. JAMA. 2006;295(2):172 [MEDLINE]
Clinical Practice: Acute pulmonary embolism. N Engl J Med 2008;359:2804–2813 [MEDLINE]
Comparative study on risk factors and early outcome of symptomatic distal versus proximal deep vein thrombosis: results from the OPTIMEV study. Thromb Haemost. 2009 Sep;102(3):493-500. doi: 10.1160/TH09-01-0053 [MEDLINE]
RIETE Investigators. Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010; 170: 1383–1389 [MEDLINE]
Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest. 2010;137(5):1145 [MEDLINE]
Gadolinium-enhanced magnetic resonance angiography for pulmonary embolism. A multicenter prospective study (PIOPED III). Ann Intern Med 2010;152:434-443 [MEDLINE]
Reproducibility of CT signs of right ventricular dysfunction in acute pulmonary embolism. AJR Am J Roentgenol 2010; 194:1500-1506 [MEDLINE]
Prognostic factors for pulmonary embolism: the PREP study, a prospective multicenter cohort study. Am J Respir Crit Care Med 2010; 181:168-173 [MEDLINE]
Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med. 2010 May 4;152(9):578-89. doi: 10.7326/0003-4819-152-9-201005040-00008 [MEDLINE]
Deep vein thrombosis: a clinical review. J Blood Med. 2011; 2: 59–69 [MEDLINE]
Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med. 2011;171(9):831 [MEDLINE]
Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants’ data from seven trials. BMJ. 2011 May 24;342:d3036. doi: 10.1136/bmj.d3036 [MEDLINE]
Obesity and pulmonary embolism: the mounting evidence of risk and the mortality paradox. Thromb Res. 2011;128:518–523 [MEDLINE]
Impact of vena cava filters on in-hospital case fatality rate from pulmonary embolism. Am J Med. 2012 May;125(5):478-84. Epub 2012 Feb 4 [MEDLINE]
Factors in the technical quality of gadolinium enhanced magnetic resonance angiography for pulmonary embolism in PIOPED III. Int J Cardiovasc Imaging. 2012 Feb;28(2):303-12. doi: 10.1007/s10554-011-9820-7. Epub 2011 Feb 24 [MEDLINE]
A meta-analysis of anticoagulation for calf deep venous thrombosis. J Vasc Surg. 2012 Jul;56(1):228-37.e1; discussion 236-7. doi: 10.1016/j.jvs.2011.09.087. Epub 2011 Dec 29 [MEDLINE]
Use of Glucocorticoids and Risk of Venous Thromboembolism: A Nationwide Population-Based Case-Control Study. JAMA Intern Med. 2013 Apr 1:1-1 [MEDLINE]
Acute pulmonary embolism: external validation of an integrated risk stratification model. Chest 2013 Jun 13. doi: 10.1378/chest.12-2938 [MEDLINE]
Identification of intermediate-risk patients with acute symptomatic pulmonary embolism. Eur Respir J. 2014 Sep;44(3):694-703. doi: 10.1183/09031936.00006114. Epub 2014 Apr 2 [MEDLINE]
Vena cava filters in unstable elderly patients with acute pulmonary embolism. Am J Med. 2014 Mar;127(3):222-5 [MEDLINE]
Non-steroidal anti-inflammatory drugs and risk of venous thromboembolism: a systematic review and meta-analysis. Rheumatology (Oxford). 2015 Apr;54(4):736-42. doi: 10.1093/rheumatology/keu408. Epub 2014 Sep 24 [MEDLINE]
Diagnostic prediction models for suspected pulmonary embolism: systematic review and independent external validation in primary care. BMJ. 2015;351:h4438 [MEDLINE]
Trends in incidence versus case fatality rates of pulmonary embolism: Good news or bad news? Thromb Haemost. 2016 Jan;115(2):233-5 [MEDLINE]
Diagnosis
An official American Thoracic Society/Society of Thoracic Radiology clinical practice guideline: evaluation of suspected pulmonary embolism in pregnancy. Am J Respir Crit Care Med. 2011 Nov 15;184(10):1200-8. doi: 10.1164/rccm.201108-1575ST [MEDLINE]
Comparison of Guidelines for Evaluation of Suspected Pulmonary Embolism in Pregnancy: A Cost-effectiveness Analysis. Chest. 2022 Jun;161(6):1628-1641. doi: 10.1016/j.chest.2021.11.036 [MEDLINE]
Clinical Decision Rules
Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-20 [MEDLINE]
Criteria for the safe use of D-dimer testing in emergency department patients with suspected pulmonary embolism: a multicenter US study. Ann Emerg Med. 2002;39:144-152 [MEDLINE]
Impact of a rapid rule-out protocol for pulmonary embolism on the rate of screening, missed cases, and pulmonary vascular imaging in an urban US emergency department. Ann Emerg Med. 2004 Nov;44(5):490-502 [MEDLINE]
Clinical gestalt and the diagnosis of pulmonary embolism: does experience matter? Chest. 2005;127:1627-30 [MEDLINE]
Simple and accurate prediction of the clinical probability of pulmonary embolism. Am J Respir Crit Care Med. 2008;178:290-294 [MEDLINE]
Prospective multicenter evaluation of the pulmonary embolism rule-out criteria. J Thromb Haemost. 2008 May;6(5):772-80. doi: 10.1111/j.1538-7836.2008.02944.x [MEDLINE]
Assessment of the pulmonary embolism rule-out criteria rule for evaluation of suspected pulmonary embolism in the emergency department. Am J Emerg Med. 2008;26(2):181 [MEDLINE]
Further validation and simplification of the Wells clinical decision rule in pulmonary embolism. Thromb Haemost. 2008;99:229-34 [MEDLINE]
Critical issues in the evaluation and management of adult patients presenting to the emergency department with suspected pulmonary embolism. Ann Emerg Med. 2011 Jun;57(6):628-652.e75. doi: 10.1016/j.annemergmed.2011.01.020 [MEDLINE]
Performance of 4 clinical decision rules in the diagnostic management of acute pulmonary embolism: a prospective cohort study. Ann Intern Med. 2011;154:709-18 [MEDLINE]
The pulmonary embolism rule-out criteria (PERC) rule does not safely exclude pulmonary embolism. J Thromb Haemost. 2011;9(2):300 [MEDLINE]
Pulmonary embolism rule-out criteria (PERC) in pulmonary embolism—revisited: a systematic review and meta-analysis. Emerg Med J. 2013;30:701-6 [MEDLINE]
Impact of delay in clinical presentation on the diagnostic management and prognosis of patients with suspected pulmonary embolism. Am J Respir Crit Care Med. 2013 Jun 15;187(12):1369-73. doi: 10.1164/rccm.201212-2219OC [MEDLINE]
Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015 Nov 3;163(9):701-11. doi: 10.7326/M14-1772. Epub 2015 Sep 29 [MEDLINE]
Risk stratification of patients with acute symptomatic pulmonary embolism based on presence or absence of lower extremity DVT: systematic review and meta-analysis. Chest. 2016;149:192–200 [MEDLINE]
Wells Rule and d-Dimer Testing to Rule Out Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis. Ann Intern Med. 2016 Aug;165(4):253-61. Epub 2016 May 17 [MEDLINE]
Clinical Decision Rules for Pulmonary Embolism in Hospitalized Patients: A Systematic Literature Review and Meta-analysis. Thromb Haemost. 2017;117(11):2176 [MEDLINE]
Simplified diagnostic management of suspected pulmonary embolism (the YEARS study): a prospective, multicentre, cohort study. Lancet. 2017;390(10091):289 [MEDLINE]
Effect of the Pulmonary Embolism Rule-Out Criteria on Subsequent Thromboembolic Events Among Low-Risk Emergency Department Patients: The PROPER Randomized Clinical Trial. JAMA. 2018 Feb 13;319(6):559-566. doi: 10.1001/jama.2017.21904 [MEDLINE]
Clinical Grading/Risk Stratification of Pulmonary Embolism Severity
Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 2005;172(8):1041–1046 [MEDLINE]
Simplification of the pulmonary embolism severity index for prognostication in patients with acute symptomatic pulmonary embolism. Arch Intern Med 2010;170(15):1383 – 1389 [MEDLINE]
Free-floating thrombus and embolic risk in patients with angiographically confirmed proximal deep venous thrombosis. A prospective study. Arch Intern Med. 1997 Feb 10;157(3):305-8 [MEDLINE]
Fever and deep venous thrombosis. Findings from the RIETE registry. J Thromb Thrombolysis. 2011 Oct;32(3):288-92. doi: 10.1007/s11239-011-0604-7 [MEDLINE]
Venous thromboembolism increases the risk of atrial fibrillation: the Tromso study. J Am Heart Assoc. 2014;3(1):e000483. Epub 2014 Jan 2 [MEDLINE]
Prophylaxis
A comparison of two different prophylactic dose regimens of low molecular weight heparin in bariatric surgery. Obes Surg 2002; 12:19 [MEDLINE]
Cost-effectiveness of ultrasound in preventing femoral venous catheter-associated pulmonary embolism. Am J Respir Crit Care Med 2003;168:1481–1487 [MEDLINE]
Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit. J Intensive Care Med. 2006 Nov-Dec;21(6):352-8 [MEDLINE]
Enoxaparin thromboprophylaxis in gastric bypass patients: Extended duration, dose stratification, and antifactor Xa activity. Surg Obes Relat Dis 2008; 4:625 [MEDLINE]
Intermittent pneumatic compression or graduated compression stockings for deep vein thrombosis prophylaxis? A systematic review of direct clinical comparisons. Ann Surg. 2010 Mar;251(3):393-6. doi: 10.1097/SLA.0b013e3181b5d61c [MEDLINE]
EXCLAIM Trial. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010 Jul 6;153(1):8-18. doi: 10.7326/0003-4819-153-1-201007060-00004 [MEDLINE]
PROTECT Trial: Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med. 2011 Apr 7;364(14):1305-14. doi: 10.1056/NEJMoa1014475 [MEDLINE]
Screening and prevention of venous thromboembolism in critically ill patients: a decision analysis and economic evaluation. Am J Respir Crit Care Med. 2011 Dec 1;184(11):1289-98. doi: 10.1164/rccm.201106-1059OC [MEDLINE]
LIFENOX: Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med. 2011 Dec 29;365(26):2463-72. doi: 10.1056/NEJMoa1111288 [MEDLINE]
ADOPT Trial. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med. 2011 Dec 8;365(23):2167-77. doi: 10.1056/NEJMoa1110899 [MEDLINE]
Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev. 2012 Sep 12;9:CD007557. doi: 10.1002/14651858.CD007557.pub2 [MEDLINE]
Efficacy and safety of high-dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014;111(1):88 [MEDLINE]
DVT Surveillance Program in the ICU: Analysis of Cost-Effectiveness. PLoS One. 2014 Sep 30;9(9):e106793. doi: 10.1371/journal.pone.0106793. eCollection 2014 [MEDLINE]
Cost-effectiveness of Dalteparin vs Unfractionated Heparin for the Prevention of Venous Thromboembolism in Critically Ill Patients. JAMA. 2014 Nov 1. doi: 10.1001/jama.2014.15101 [MEDLINE]
High dose subcutaneous unfractionated heparin for prevention of venous thromboembolism in overweight neurocritical care patients. J Thromb Thrombolysis. 2015;40(3):302 [MEDLINE]
Safety and Efficacy of High-Dose Unfractionated Heparin for Prevention of Venous Thromboembolism in Overweight and Obese Patients. Pharmacotherapy. 2016;36(7):740 [MEDLINE]
The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial. Am Heart J. 2017 Mar;185:93-100. doi: 10.1016/j.ahj.2016.12.004. Epub 2016 Dec 18 [MEDLINE]
Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations. Ann Pharmacother. 2018 Sep;52(9):898-909. doi: 10.1177/1060028018768449 [MEDLINE]
VTE Prophylaxis in Critically Ill Adults: A Systematic Review and Network Meta-analysis. Chest. 2022 Feb;161(2):418-428. doi: 10.1016/j.chest.2021.08.050 [MEDLINE]
Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis. BMJ. 2022 Jul 4;378:e070022. doi: 10.1136/bmj-2022-070022 [MEDLINE]
Effect of Intermittent Pneumatic Compression in Addition to Pharmacologic Prophylaxis for Thromboprophylaxis in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis. Crit Care Explor. 2022 Oct 3;4(10):e0769. doi: 10.1097/CCE.0000000000000769. eCollection 2022 Oct [MEDLINE]
Upper Extremity Deep Venous Thrombosis (DVT)
The long term clinical course of acute deep vein thrombosis of the arm: prospective cohort study. BMJ. 2004;329:484-5 [MEDLINE]
Upper extremity DVT in oncological patients: analysis of risk factors. Data from the RIETE registry. Exp Oncol. 2006;28:245-7
Upper extremity deep venous thrombosis. Semin Thromb Hemost. 2006;32:729-36 [MEDLINE]
Current perspective of venous thrombosis in the upper extremity. J Thromb Haemost. 2008;6:1262-6 [MEDLINE]
Accuracy of diagnostic tests for clinically suspected upper extremity deep vein thrombosis: a systematic review. J Thromb Haemost. 2010;8:684-92 [MEDLINE]
Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet 2013;382(9889):311-325 [MEDLINE]
Safety and feasibility of a diagnostic algorithm combining clinical probability, d-dimer testing, and ultrasonography for suspected upper extremity deep venous thrombosis: a prospective management study. Ann Intern Med. 2014 Apr 1;160(7):451-7. doi: 10.7326/M13-2056 [MEDLINE]
