Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
For Patients with Acute Pulmonary Embolism (PE) who Exhibit High-Risk Clinical Features (Right Ventricular Dysfunction and/or Elevated Cardiac Biomarkers), But are Hemodynamically Stable (i.e. AHA/ACC Pulmonary Embolism Categories C3-D), Transferring to a Center Which Can Provide Advanced Therapies May Be Considered to Ensure Access to Appropriate Interventions (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.1.3)
Unstable Patients with Acute Pulmonary Embolism (PE) (AHA/ACC Pulmonary Embolism Category E) Should Not Be Transferred to Another Medical Center Before Stabilizing Their Condition (Class of Recommendation: 3 = Harm; Level of Evidence: C-EO; Section 4.1.3)
Hospital Units
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patients with Acute Pulmonary Embolism (PE) who are Receiving Thrombolytic Therapy (Systemic or Catheter-Directed Thrombolysis), Placement in a Unit Which Can Provide Close Monitoring (Such as an Intensive Care Unit or Intermediate Level of Care Unit) is Recommended to Monitor for Adverse Events (Class of Recommendation: 1; Level of Evidence: C-EO; Section 4.1.2)
In Patients Admitted to the Hospital with Acute Pulmonary Embolism (PE) who Undergo Mechanical Thrombectomy and are Hemodynamically Stable, Admission to a Level of Care Which Can Provide Continuous Telemetry and Nursing Care Familiar with the Postprocedural Complications of the Device Used is Reasonable (Class of Recommendation: 2a; Level of Evidence: B-R; Section 4.1.2)
Pulmonary Embolism Response Team (PERT)
General Comments
Pulmonary Embolism Response Teams (PERT) Have Been Put into Practice in Many Centers to Facilitate the More Eficient Management of Patients with Acute Pulmonary Embolism (Particularly with Regard to Rapid Identification and Deployment of Systemic Thrombolytics, Catheter-Directed Thrombolysis, and Surgical Embolectomy)
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]
Set-Up of a Multidisciplinary Team and Program for the Management of High-Risk (and in Selected Cases, Intermediate-Risk Acute Pulmonary Embolism) Should Be Considered, Depending on the Resources and Expertise Available in Each Hospital (Class IIa, Level C)
Recommendations (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
Utilize a Multidisciplinary Pulmonary Embolism Response Team (PERT) in Patients with Intermediate or High-Risk Acute Pulmonary Embolism, as Well as for Acute Pulmonary Embolism Patients in Whom There is Uncertainty Regarding Treatment
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patients with Acute Pulmonary Embolism (PE) Who are at Increased Risk of Adverse Outcomes (i.e. AHA/ACC Pulmonary Embolism Categories C-E), a Multidisciplinary Pulmonary Embolism Response Team (PERT) Assessment is Recommended to Improve In-Hospital Clinical Care Delivery (Class of Recommendation: 1; Level of Evidence: B-NR; Section 4.1.4)
AHA/ACC Pulmonary Embolism Categories A or B with Multiple Comorbidities May Also Benefit from a PERT Evaluation
For Example: Category B with Intracranial Hemorrhage
Respiratory Support (Supplemental Oxygen and/or Mechanical Ventilatory Support)
Randomized Trial of Supplemental Oxygen in Non-Hypoxemic Intermediate-Risk Pulmonary Embolism (Chest, 2024) [MEDLINE]: n = 70 (trial stopped prematurely, due to the COVID pandemic)
48 hrs h After Randomization, Normalization of the Right Ventricle Size Occurred in 42.4% of the Patients Assigned to Oxygen and 21.6% of the Patients Assigned to Ambient Air (p = 0.08)
In the Oxygen Group, the Mean Right Ventricle/Left Ventricle Ratio Decreased from 1.28 ± 0.28 at Baseline to 1.01 ± 0.16 at 48 hrs (p < 0.001)
In the Ambient Air Group, Mean Right Ventricle/Left Ventricle Ratios were 1.21 ± 0.18 at Baseline and 1.08 ± 0.19 at 48 hrs (p < 0.01)
At 90 Days, One Major Bleeding Event and One Death (Both in the Ambient Air Group) Had Occurred
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
Sedation and Ventilatory Strategies
In Patients with Acute Pulmonary Embolism (PE) in AHA/ACC Pulmonary Embolism Categories C-E Who Require Sedation for Intubation, Hemodynamic Supportive Therapies (Vasopressors, Inotropes, and/or Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) Should Be Available to Support the Patient in the Event the Patient Becomes Unstable (Class of Recommendation: 1; Level of Evidence: C-LD; Section 4.2.3)
For Patients with Acute Pulmonary Embolism (PE) and Moderate-Severe Hypoxemia, the Use of Heated High-Flow Nasal Cannula (HFNC) Oxygenation Rather than Standard Nasal Cannula Oxygenation Can Be Beneficial to Improve Oxygenation (Class of Recommendation: 2a; Level of Evidence: C-LD; Section 4.2.3)
In Patients with Acute Pulmonary Embolism (PE) in AHA/ACC Pulmonary Embolism Categories C-E, Deep Sedation and Mechanical Ventilation Should Not Be Performed, Unless Clinically Indicated, in Order to Avoid Hemodynamic Collapse (Class of Recommendation: 3 = Harm; Level of Evidence: C-LD; Section 4.2.3)
General Goals of Anticoagulation in Venous Thromboembolism
Prevention of Early Complications of Venous Thromboembolism
General Comments
The Benefits of Anticoagulation are the Greatest During the Initial Period of Anticoagulation
Anticoagulation Decreases Risk of Deep Venous Thrombosis Recurrence and the Decreases the Mortality Rate (Lancet, 1960) [MEDLINE]
In Patients Admitted for Acute Pulmonary Embolism Through the Emergency Department, Early Anticoagulation was Associated with Decreased Mortality Rate (Chest, 2010) [MEDLINE]: n = 400 emergency department patients with acute pulmonary embolism (treated with unfractionated heparin from 2002-2005)
Overall, the In-Hospital Mortality Rate was 3.0% and 30-Day Mortality Rate was 7.7% in the Study
Patients Who Received Heparin in the Emergency Department Had Decreased In-Hospital Mortality Rate (1.4% vs 6.7%; P = 0.009) and Decreased 30-Day Mortality Rate (4.4% vs 15.3%; P < 0.001), as Compared to Patients Who Received Heparin After Admission
Patients Who Achieved a Therapeutic PTT within 24 hrs Had Decreased In-Hospital Mortality Rate (1.5% vs 5.6%; P = 0.093) and Decreased 30-Day Mortality Rate (5.6% vs 14.8%; P = .037), as Compared to Patients Who Achieved a Therapeutic PTT After 24 hrs
In Multiple Logistic Regression Models, Receiving Heparin in the Emergency Department Remained Predictive of Decreased Mortality Rate, and Intensive Care Unit Admission Remained Predictive of Increased Mortality Rate
Large Prospective Cohort Study of the Effects of Anticoagulation on Major Cardiovascular Events in Patients with Venous Thromboembolism (Chest, 2022) [MEDLINE]: n = 3,790
Treatment of Venous Thromboembolism for >3 Months was Associated with a Decreased Risk of Major Cardiovascular Events (Non-Fatal Acute Coronary Syndrome, Non-Fatal Stroke, and All-Cause Mortality)
Treatment of Venous Thromboembolism with Direct Oral Anticoagulant (DOAC) vs Coumadin was Associated with Decreased Risk of Major Cardiovascular Events
Prevention of Late Complications of Venous Thromboembolism
Prevention of Recurrent Deep Venous Thrombosis (DVT)
Anticoagulation Decreased Risk of DVT Recurrence and Mortality Rate (Lancet, 1960) [MEDLINE]
Anticoagulation Decreased the Risk of Recurrent Venous Thromboembolism to 3.4% and Risk of Fatal Venous Thromboembolism to 0.4% (Ann Intern Med, 2010) [MEDLINE]
Systematic Review and Meta-Analysis of Anticoagulation Regimens for Venous Thromboembolism (JAMA, 2014) [MEDLINE]: n = 45 trials (44,989 patients)
No Statistically Significant Differences (in Terms of Safety/Efficacy) Between Anticoagulation Regimens (Low Molecular Weight Heparin/Coumadin, Unfractionated Heparin/Coumadin, Fondaparinux/Coumadin, Low Molecular Weight Heparin with Dabigatran/Edoxaban, Apixaban, Rivaroxaban, or Low Molecular Weight Heparin Alone)
Combination of Unfractionated Heparin/Coumadin Appeared to Have the Highest Risk of Venous Thromboembolism Recurrence (Hazard Ratio 1.42)
Apixaban/Rivaroxaban Regimens were Associated with the Lowest Risk of Hemorrhage
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]
Intermediate/Low-Risk Pulmonary Embolism
In Patient without Hemodynamic Instability and with Intermediate/High Clinical Probability of Acute Pulmonary Embolism, Initiation of Anticoagulation is Recommended without Delay While Diagnostic Work-Up is in Progress (Class I, Level C)
If Anticoagulation is Initiated Parenterally, Low Molecular Weight Heparin or Fondaparinux is Recommended Over Unfractionated Heparin for Most Patients (Class I, Level A)
When Oral Anticoagulation is Started in a Patient with Acute Pulmonary Embolism Who is Eligible for a Direct Oral Anticoagulant (Apixaban, Dabigatran, Edoxaban, Rivaroxaban), a Direct Oral Anticoagulant is Recommended in Preference to Coumadin (Class I, Level A)
When Patients are Treated with Coumadin, Overlapping with Parenteral Anticoagulation is Recommended Until an INR of 2.5 (Range 2-3) is Reached (Class I, Level A)
Direct Oral Anticoagulant are Not Recommended in Patients with Severe Renal Impairment, During Pregnancy and Lactation, and in Patients with Antiphospholipid Antibody Syndrome (Class III, Level C)
Routine Use of Primary Systemic Thrombolysis is Not Recommended in Patients with Low-Intermediate Risk Acute Pulmonary Embolism (Class III, Level B)
Recommendations (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
Anticoagulation
Anticoagulation Should Be Initiated as Soon as Acute Pulmonary Embolism is Diagnosed (Unless Contraindicated)
Anticoagulation Should Be Initiated Even Prior to the Confirmed Diagnosis When the Clinical Suspicion of Acute Pulmonary Embolism is High and the Bleeding Risk is Low
Utilize Evidence-Based Institution-Specific Anticoagulation Guidelines to Assist in Anticoagulant Choice, Dosing, Administration, and Appropriate Laboratory Monitoring Strategies to Achieve Therapeutic Anticoagulation as Quickly as Possible
Risk Stratification for Anticoagulation-Associated Hemorrhage (Chest Antithrombotic Therapy for VTE Disease 2016 Guidelines) (Chest, 2016) [MEDLINE]
Risk Factors for Anticoagulation-Associated Hemorrhage
Apixaban and Rivaroxaban Utilize Higher Doses During the Initiation Phase of Anticoagulation (Precluding the Need for Initial Heparin Therapy)
Apixaban Initiation Phase: 10 mg BID x 7 days
Rivaroxaban Initiation Phase: 15 mg BID x 21 days
Cautions
If a Delay in Initiation of Oral Therapy is Possible (or Anticipated), Low Molecular Weight Heparin Should Be Administered in the Interim to Assure Prompt Initiation of Anticoagulation
This is Especially Critical Since the Peak Onset of Action of Apixaban is 3-4 hrs
Contraindications
Importantly, Oral Factor Xa Inhibitors or Oral Direct Thrombin Inhibitors are Contraindicated for the Initial Treatment of Hemodynamically Unstable Pulmonary Embolism Patients or Patients with Massive Iliofemoral Deep Venous Thrombosis (i.e. Phlegmasia Cerulea Dolens) in Which Their Efficacy Has Not Been Adequately Studied and Their Use May Interfere with Potential Interventional Therapy (Such as Thrombolytic Therapy)
In Hemodynamically Unstable Pulmonary Embolism, Low Molecular Weight Heparin (Usually Enoxaparin) Used Initially with Later Initiation of Treatment Phase Therapy After Interventions and/or Stabilization of the Patient
In Phlegmasia Cerulea Dolens, Unfractionated Heparin Drip is Generally Used Initially with Later Initiation of Treatment Phase Therapy After Interventions and/or Stabilization of the Patient
Because Dabigatran and Edoxaban Have Not Been Studied Using Higher Doses for Initiation of Anticoagulation, a Parenteral Anticoagulant (Such as Enoxaparin) Must Be Utilized for at Least 5 Days, After Which the Patient is Then Transitioned to Dabigatran or Edoxaban for the Treatment Phase
Medications are Not Given Concomitantly (i.e. No Overlap)
When Using Coumadin, Parenteral Anticoagulation (Usually Unfractionated Heparin or Low Molecular Weight Heparin) is Required with the Initiation of Coumadin on the Same Day (Both Agents are Overlapped Until at Least 5 Days of Concomitant Therapy Have Elapsed; Parenteral Agent is Continued Until the INR Has Been ≥2.0 for at Least 24 hrs)
Inability to Take Oral Anticoagulant (Due to Malabsorption, Ileus, etc)
Selected Patients with Cancer-Associated Thrombosis
These Patients Utilize Low Molecular Weight Heparin (Enoxaparin, etc) for Initiation Phase Therapy with Continuation of This Agent for Ongoing Treatment Phase
Depending on the specific Low Molecular Weight Heparin Utilized, the Daily Dose May Be Adjusted After the First 30 days of Administration
Choice of Anticoagulant (Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report) (Chest, 2016) [MEDLINE] (Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report) (Chest, 2021) [MEDLINE] (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
Advantages of Low Molecular Weight Heparin Over Unfractionated Heparin Drip (Meta-Analysis; 29 Studies) (Cochrane Database Syst Rev, 2017) [MEDLINE]
Fewer Thrombotic Complications (Recurrence, Extension, Embolization) (3.7 vs 5.1%; Odds Ratio 0.7; 95% CI 0.56-0.9)
Improved Thrombus Regression (51 vs 42%; Odds Ratio 0.71l; 95% CI 0.61-0.82)
Reduced Rates of Major Hemorrhage (1.5 vs 2.1%; Odds Ratio 0.69; 95% CI 0.5-0.95)
Non-Significant Reduction in Mortality Rate (4.8 vs 5.7%; Odds Ratio 0.84; 95% CI 0.7-1.01)
Recommendations (American Society of Hematology Guidelines for the Management of Venous Thromboembolism, 2020) (Blood Adv, 2020) [MEDLINE]
For Patients with Venous Thromboembolism, Use of Direct Oral Anticoagulants (DOAC’s) is Recommended Over Coumadin (Conditional Recommendation; Moderate Certainty in the Evidence)
This Recommendation May Not Apply to Patients with the Following
For Patients with Venous Thromboembolism, There is No Recommendation of One Direct Oral Anticoagulant (DOAC) Over Another (Conditional Recommendation; Very Low Certainty in the Evidence)
Factors Which May Influence the Selection of a Specific Direct Oral Anticoagulant (DOAC)
Cancer
Concomitant Medications (Need for a Concomitant Drug Metabolized Through the CYP3A4 Enzyme or P-Glycoprotein)
Once vs Twice Daily Dosing
Out-of-Pocket Cost
Renal Function
Requirement for Lead-In Parenteral Anticoagulation
For Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism with Stable Cardiovascular Disease Who Initiate Anticoagulation and were Previously Taking Aspirin for Cardiovascular Risk Modification, Suspending Aspirin is Recommended Over Continuing it for the Duration of Anticoagulation Therapy (Conditional Recommendation; Very Low Certainty in the Evidence)
A Critical Review of the Indication for Aspirin Therapy is Needed at the Time Anticoagulant Therapy is Initiated, Considering the Increased Risk of Bleeding vs the Potential Benefit in Terms of Cardiovascular Prevention
This Recommendation Does Not Apply to Patients with a Recent Acute Coronary Event or Coronary Intervention
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
Parenteral Therapy
In Patient with Acute Pulmonary Embolism (PE) in AHA/ACC Categories C1-E1 Who Requires Parenteral Anticoagulant Therapy Initially, Low Molecular Weight Heparin is Recommended Over Unfractionated Heparin to Decrease Recurrent Venous Thromboembolism and the Risk of Major Bleeding (Class of Recommendation: 1; Level of Evidence: B-R; Section 4.2.1)
Oral Therapy
In Patient with Acute Pulmonary Embolism (PE) Who is Eligible for Oral Anticoagulation, Direct Oral Anticoagulants (DOAC) is Recommended Over Vitamin K Antagonists (Coumadin), Unless Contraindicated, to Prevent Recurrent Venous Thromboembolism and Decrease the Risk of Major Bleeding (Class of Recommendation: 1; Level of Evidence: B-R; Section 4.2.1)
Breastfeeding
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Acute Pulmonary Embolism (PE) Who is Breastfeeding and Requires Anticoagulation, Low-Molecular Weight Heparin, Unfractionated Heparin, or Coumadin are Recommended Over a Direct Oral Anticoagulant (DOAC) to Prevent Potential Bleeding in the Infant (Class of Recommendation: 3 = Harm; Level of Evidence: C-LD; Section 4.2.1)
In Patients with Venous Thromboembolism (Lower Extremity Deep Venous Thrombosis or Acute Pulmonary Embolism) in the Setting of Cancer (Cancer-Associated Thrombosis), Oral Xa Inhibitors (Apixaban, Edoxaban, Rivaroxaban) are Recommended Over Low Molecular Weight Heparin for the Initiation and Treatment Phases of Anticoagulant Therapy (Strong Recommendation; Moderate-Certainty Evidence)
Edoxaban and Rivaroxaban Appear to Be Associated with a Higher Risk of Gastrointestinal Major Bleeding than Low Molecular Weight Heparins in Patients with Cancer-Associated Thrombosis and a Luminal Gastrointestinal Malignancy, While Apixaban Does Not
Consequently, Apixaban or Low Molecular Weight Heparins May Be the Preferred Options in Patients with Luminal Gastrointestinal Malignancies
Systematic Review/Meta-Analysis Comparing Rates of Hemorrhage of Direct Oral Anticoagulants (DOAC’s) vs Coumadin When Used in the Setting of Renal Insufficiency (Chest, 2016) [MEDLINE]
CrCl 50-80 mL/min: direct oral anticoagulants had a significantly decreased risk of major bleeding, as compared to coumadin
CrCl <50 mL/min: direct oral anticoagulants had a non-significantly decreased risk of major bleeding, as compared to coumadin
Apixaban Had the Lowest Rate of Major Bleeding in this Subgroup
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Mild-Moderate (Stage 2-3) Chronic Kidney Disease (CKD) and Acute Pulmonary Embolism (PE) Who Requires Oral Anticoagulation, a Direct Oral Anticoagulant (DOAC) is Recommended Over a Vitamin K Antagonist (Coumadin) to Decrease Major Bleeding (Class of Recommendation: 1; Level of Evidence: A; Section 4.2.1)
In Patient with Severe Kidney Disease (Stage 4-5) or Endstage Kidney Disease on Hemodialysis and Confirmed Acute Pulmonary Embolism (PE) Who Requires Oral Anticoagulation, it is Uncertain Whether Apixaban is Better than a Vitamin K Antagonist (Coumadin) to Decrease Major Bleeding (Class of Recommendation: 2b; Level of Evidence: B-NR; Section 4.2.1)
In Patient with Acute Pulmonary Embolism (PE) Who Have Severe Chronic Kidney Disease (CKD) (CrCl <30 mL/min) and is Being Treated with Low-Molecular Weight Heparin, it is Reasonable to Monitor Anti-Xa Levels to Guide Dose Adjustment in Order to Decrease the Risk of Bleeding (Class of Recommendation: 2a; Level of Evidence: C-LD; Section 4.2.1)
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Child-Pugh Class A Chronic Liver Disease and Acute Pulmonary Embolism (PE), Treatment with a Direct Oral Anticoagulant (DOAC) Instead of a Vitamin K Antagonist (Coumadin) is Reasonable to Decrease the Risk of Bleeding (Class of Recommendation: 2a; Level of Evidence: C-LD; Section: 4.2.1)
In Patient with Child-Pugh Class B Chronic Liver Disease and Acute Pulmonary Embolism (PE), Treatment with a Direct Oral Anticoagulant (DOAC) Instead of a Vitamin K Antagonist (Coumadin) May Be Reasonable to Decrease the Risk of Bleeding (Class of Recommendation: 2b; Level of Evidence: C-LD; Section: 4.2.1)
In Patient with Child-Pugh Class C Chronic Liver Disease and Acute Pulmonary Embolism (PE), Treatment with a Direct Oral Anticoagulant (DOAC) Instead of a Vitamin K Antagonist (Coumadin) is Not Recommended Due to Potential for an Increased Risk of Bleeding (Class of Recommendation: 3 = Harm; Level of Evidence: C-LD; Section: 4.2.1)
Coronary Artery Events Occur More Frequently with Dabigatran than with Coumadin
This is Not Seen with Other Direct Oral Anticoagulants (DOAC’s)
If Possible, Antiplatelet Therapy (for Coronary Artery Disease) Should Be Avoided in Patients on Anticoagulants Because of Increased Risk of Bleeding
Cost/Coverage Issues
Preferred Agents
Variable
Clinical Data
Cost-Effectiveness of Rivaroxaban Compared to Enoxaparin/Coumadin in Treatment of Venous Thrombembolism (J Med Econ, 2014) [MEDLINE]
Rivaroxaban Cost $2,448 Per-Patient Less and was Associated with 0.0058 More QALY’s, as Compared with Enoxaparin + Coumadin
Cost-Effectiveness of Novel Oral Anticoagulants, Compared to Coumadin, in Non-Valvular Atrial Fibrillation and Venous Thromboembolism (J Med Econ, 2015) [MEDLINE]
Medical Costs are Reduced When Direct Oral Anticoagulants are Used Instead of Coumadin for the Treatment of Non-Valvular Atrial Fibrillation/Venous Thromboembolism, with Apixaban Being Associated with the Greatest Reduction in Medical Costs
UK Study of Cost-Effectiveness of Rivaroxaban Compared to Enoxaparin/Coumadin in Treatment of Venous Thromboembolism (Thromb J, 2015) [MEDLINE]
Rivaroxaban was a Cost-Effective Choice for Acute Treatment of Venous Thromboembolism and Secondary Prevention of Venous Thromboembolism, as Compared with Low Molecular Weight Heparin/Coumadin Treatment, Regardless of the Treatment Duration
Dabigatran, Rivaroxaban, and Edoxaban May Be Associated with Higher Risk of Gastrointestinal Hemorrhage than Coumadin
Data Supporting This is from Atrial Fibrillation Trials (But Venous Thromboembolism Trials Do Not Support This)
Metastatic Brain Tumor
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Primary or Metastatic Brain Tumors and Acute Pulmonary Embolism (PE) Who is Otherwise Eligible for Oral Anticoagulation, a Direct Oral Anticoagulant (DOAC) May Be Considered Over Low Molecular Weight Heparin to Decrease the Risk of Intracranial Hemorrhage (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Obesity (Body Mass Index/BMI >30 kg/m2) and Acute Pulmonary Embolism (PE) Who is Receiving Oral Anticoagulant Therapy, Treatment with a Direct Oral Anticoagulant (DOAC) (Unless Contraindicated) Over a Vitamin K Antagonist (Coumadin) is Reasonable to Prevent Recurrent Pulmonary Embolism and Decrease the Risk of Major Bleeding (Class of Recommendation: 2a; Level of Evidence: B-NR; Section 4.2.1)
In Patient with Class III Obesity (Body Mass Index/BMI >40 kg/m2) and Acute Pulmonary Embolism (PE) Who is Receiving Low Molecular Weight Heparin Therapy, Decreasing the Dose of Low Molecular Weight Heparin May Be Reasonable to Decrease the Risk of Bleeding (Class of Recommendation: 2a; Level of Evidence: B-NR; Section 4.2.1)
In Patients Who Weigh >150 kg or Have a Body Mass Index (BMI) >40 kg/m2 and are Receiving Low-Molecular Weight Heparin for Treatment of Acute Pulmonary Embolism (PE), the Benefit of Monitoring Anti-Factor Xa Levels is Not Established to Avoid Supratherapeutic Levels of Low-Molecular Weight Heparin After Initial Therapy (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Pregnant Patient with Acute Pulmonary Embolism (PE) Who Can Receive Anticoagulation, Either Low-Molecular Weight Heparin or Unfractionated Heparin are Recommended to Prevent Recurrent Venous Thromboembolism (Class of Recommendation: 1; Level of Evidence: C-LD; Section 4.2.1)
In Pregnant Patient with Acute Pulmonary Embolism (PE), Direct Oral Anticoagulants (DOAC’s) and Coumadin are Potentially Harmful and May Result in Miscarriages or Fetal Anomalies (Class of Recommendation: 3 = Harm; Level of Evidence: C-LD; Section 4.2.1)
In Pregnant Patients Treated with Low-Molecular Weight Heparin for Acute Pulmonary Embolism (PE), the Usefulness of Monitoring the Peak Anti-Factor Xa Level at Least Once Per Trimester is Not Well Established to Guide Dose Adjustment and Decrease the Risk of Bleeding and/or Thromboembolism (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
In Patient with Acute Pulmonary Embolism (PE) and Established Thrombotic Antiphospholipid Antibody Syndrome, a Vitamin K Antagonist (Coumadin) is Recommended in Preference to a Direct Oral Anticoagulant (DOAC) for the Prevention of Venous and Arterial Thrombosis (Class of Recommendation: 1; Level of Evidence: A; Section 4.2.1)
In Patient with Acute Pulmonary Embolism (PE) Determined to Have Only a Single Anticardiolipin Antibody or a β2-Glycoprotein Antibody, a Direct Oral Anticoagulant (DOAC) Might Be a Reasonable Alternative to a Vitamin K Antagonist (Coumadin) to Prevent Recurrent Pulmonary Embolism (PE) (Class of Recommendation: 2b; Level of Evidence: B-R; Section 4.2.1)
Recommendations (2026 AHA/ACC/ACCP/ACEP/CHEST/SCAI/SHM/SIR/SVM/SVN Guideline for the Evaluation and Management of Acute Pulmonary Embolism in Adults: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines) (Circulation, 2026) [MEDLINE]
Use of Factor Xa Levels to Guide Low-Molecular Weight Heparin Therapy (see Enoxaparin)
General
In Patient with Acute Pulmonary Embolism (PE) in whom Low-Molecular Weight Heparin is Monitored, Measuring a Peak Anti-Factor Xa Level 3-5 hrs After an Low-Molecular Weight Heparin Dose Once a Steady State is Reached (≥3 Doses) is Recommended in Preference to Checking Trough or Random Levels in Order to Most Accurately Determine if the Patient is within the Expected Therapeutic Range (Class of Recommendation: 1; Level of Evidence: C-LD; Section 4.2.1)
In Most Patients with Acute Pulmonary Embolism (PE) Treated with Weight-Based Low-Molecular Weight Heparin, Laboratory Monitoring of Anti-Factor Xa Levels and Dose Adjustment is Not Indicated to Decrease the Risk of Bleeding and/or Recurrent Venous Thromboembolism (Class of Recommendation: 3 = No Benefit; Level of Evidence: A; Section 4.2.1)
In Patient with Acute Pulmonary Embolism (PE) Who Has Severe Chronic Kidney Disease (CKD) (CrCl <30 mL/min) and are Being Treated with Low-Molecular Weight Heparin, it is Reasonable to Monitor Anti-Factor Xa Levels to Guide Dose Adjustment in Order to Decrease the Risk of Bleeding (Class of Recommendation: 2a; Level of Evidence: C-LD; Section 4.2.1)
In Pregnant Patient Treated with Low-Molecular Weight Heparin for Acute Pulmonary Embolism (PE), the Usefulness of Monitoring the Peak Anti-Factor Xa Level at Least Once Per Trimester is Not Well Established to Guide Dose Adjustment and Decrease the Risk of Bleeding and/or Thromboembolism (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
In Patient Who Weighs >150 kg or Have a Body Mass Index (BMI) >40 kg/m2 and are Receiving Low-Molecular Weight Heparin for Treatment of Acute Pulmonary Embolism (PE), the Benefit of Monitoring Anti-Factor Xa Levels is Not Established to Avoid Supratherapeutic Levels of Low-Molecular Weight Heparin After Initial Therapy (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
Intensive Care Unit (ICU) Setting
In Patient with Acute Pulmonary Embolism (PE) Treated with Low-Molecular Weight Heparin in the Intensive Care Unit (ICU), the Benefit of Monitoring Anti-Factor Xa Levels is Not Established to Avoid Supratherapeutic and/or Subtherapeutic Levels (Class of Recommendation: 2b; Level of Evidence: C-LD; Section 4.2.1)
Switching Between Anticoagulants
Reasons for Switching Between Anticoagulants
Development of Acute/Chronic Kidney Disease, Which Prolongs the Half-Life of Low Molecular Weight Heparin, Fondaparinux, Factor Xa Inhibitors/Direct Thrombin Inhibitors (Direct Oral Anticoagulants/DOAC’s)
Burdens of Laboratory International Normalized Ratio (INR) Testing for Coumadin
Poor Compliance or Difficulty with International Normalized Ratio (INR) Testing for Coumadin
Cost/Changes in Medication Coverage
Need for Repeated Invasive Procedures (Which Require Interruption of Long-Acting Anticoagulants)
Pain/Inflammation at Injection Sites
Recurrence Despite Therapeutic Anticoagulation
Resolution of Active Cancer
Initial Treatment of Venous Thromboembolism (VTE) (Deep Venous Thrombosis or Acute Pulmonary Embolism)
Requirements for Initial Parenteral Anticoagulation with Specific Long-Term Anticoagulants
Parenteral Anticoagulation is Indicated Prior to Coumadin (see Coumadin)
Conversion from Parenteral Anticoagulation to Coumadin
Coumadin Should Be Started Concurrently with Parenteral Anticoagulation, Rather Than Waiting (Grade 2C Recommendation) (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]: start coumadin 5 mg qday (with a lower dose used in elderly or those with a high risk of bleeding, malnutrition, debility, congestive heart failure, or liver disease)
Coumadin Should Be Overlapped with Parenteral Anticoagulation for at Least 4-5 Days
Parenteral Anticoagulation Can Be Discontinued When INR Remains >2 for at Least 2 Consecutive Days
Parenteral Anticoagulation is Indicated Prior to Dabigatran (Pradaxa) (see Dabigatran)
Conversion from Unfractionated Heparin Drip/Argatroban Drip to Dabigatran: start dabigatran as soon as heparin drip is stopped
Conversion from Low Molecular Weight Heparin (Enoxaparin, Dalteparin, Tinzaparin) or Fondaparinux to Dabigatran: start dabigatran approximately 2 hrs prior to next scheduled dose of subcutaneous anticoagulant
Parenteral Anticoagulation is Indicated Prior to Edoxaban (Savaysa, Lixiana) (see Edoxaban)
Conversion from Unfractionated Heparin/Argatroban Drip to Edoxaban (Savaysa, Lixiana): discontinue heparin/argatroban drip and initiate edoxaban 4 hrs later
Conversion from Low Molecular Weight Heparin (Enoxaparin, Dalteparin, Tinzaparin) to Edoxaban: discontinue low molecular weight heparin and initiate edoxaban at the time of the next scheduled administration of low molecular weight heparin
Parenteral Anticoagulation is Not Indicated Prior to Apixaban (Eliquis)/Rivaroxaban (Xarelto) (see Apixaban and Rivaroxaban): monotherapy with these agents is considered safe and effective when administered as monotherapy (without heparin pre-treatment) to outpatients
EINSTEIN Trial Demonstrated that in Acute Symptomatic Deep Venous Thrombosis, Rivaroxaban “Monotherapy” was Non-Inferior to Enoxaparin (SQ) Followed by Coumadin (NEJM, 2010) [MEDLINE]
AMPLIFY Trial Demonstrated that in Acute Symptomatic Venous Thromboembolism, Apixaban “Monotherapy” was Non-Inferior to Enoxaparin (SQ) Followed by Coumadin and was Associated with Significantly Lower Risk of Bleeding (NEJM, 2013) [MEDLINE]
Parenteral Anticoagulant Dosing in Morbid Obesity (see Obesity)
Dosing Weight = Ideal Body Weight + 0.3 (Actual Body Weight – Ideal Body Weight)
Dosing weight = Ideal Body Weight + 0.4 (Actual Body Weight – Ideal Body Weight)
Long-Term Treatment of Venous Thromboembolism (VTE) (Deep Venous Thrombosis or Acute Pulmonary Embolism) without Cancer
Agents
First-Line Agents (Oral Anticoagulants)
General Comments
Risk of Bleeding with DOAC’s (and Particularly Intracranial Bleeding) is Less with DOAC’s than with Coumadin Therapy (Chest, 2021) [MEDLINE]
On the Basis of Patients with Atrial Fibrillation, Gastrointestinal Bleeding May Be Higher with Dabigatran, Edoxaban, and Rivaroxaban than with Coumadin Therapy, Although This Has Not Been Seen in Patients with Venous Thromboembolism (Chest, 2021) [MEDLINE]
However, on the Basis of Indirect Comparisons and Studies Reporting on DOAC’s for the Treatment of Cancer-Associated Thrombosis, the Risk of Bleeding May Be Lower with Apixaban than with Other DOAC’s (Chest, 2021) [MEDLINE]
Specific Reversal Agents for DOAC’s Have Been Approved (Yet Even Before the Availability of These, the Risk that a Major Bleed Will Be Fatal Appears to Be No Higher for DOAC’s than for Coumadin Therapy) (Chest, 2021) [MEDLINE]
Direct Comparison Between DOAC’s is Very Limited, But Suggests that Apixaban May Carry a Lower Risk of Bleeding than Other DOAC’s (Chest, 2021) [MEDLINE]
Recommendations (American Society of Hematology Guidelines for the Management of Venous Thromboembolism, 2020) (Blood Adv, 2020) [MEDLINE]
For Patients with Venous Thromboembolism, Use of Direct Oral Anticoagulants (DOAC’s) is Recommended Over Coumadin (Conditional Recommendation, Moderate Certainty in the Evidence)
This Recommendation May Not Apply to Patients with the Following
For Patients with Venous Thromboembolism, There is No Recommendation of One DOAC Over Another (Conditional Recommendation, Very Low Certainty in the Evidence)
Factors Which May Influence the Selection of a Specific DOAC
Cancer
Concomitant Medications (Need for a Concomitant Drug Metabolized Through the CYP3A4 Enzyme or P-Glycoprotein)
Once vs Twice Daily Dosing
Out-of-Pocket Cost
Renal Function
Requirement for Lead-In Parenteral Anticoagulation
For Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism with Stable Cardiovascular Disease Who Initiate Anticoagulation and were Previously Taking Aspirin for Cardiovascular Risk Modification, Suspending Aspirin is Recommended Over Continuing it for the Duration of Anticoagulation Therapy (Conditional Recommendation, Very Low Certainty in the Evidence)
A Critical Review of the Indication for Aspirin Therapy is Needed at the Time Anticoagulant Therapy is Initiated, Considering the Increased Risk of Bleeding vs the Potential Benefit in Terms of Cardiovascular Prevention
This Recommendation Does Not Apply to Patients with a Recent Acute Coronary Event or Coronary Intervention
In Patients with Venous Thromboembolism (Lower Extremity Deep Venous Thrombosis or Acute Pulmonary Embolism), Apixaban/Dabigatran/Edoxaban/Rivaroxaban are Recommended Over Coumadin as the Treatment-Phase (First 3 Months) Anticoagulant Therapy (Strong Recommendation, Moderate-Certainty Evidence)
Long-Term Treatment of Venous Thromboembolism (VTE) (Deep Venous Thrombosis or Acute Pulmonary Embolism) with Cancer
Agents
First-Line Agents (Oral Xa Inhibitors)
General Comments
Risk of Bleeding with DOAC’s (and Particularly Intracranial Bleeding) is Less with DOAC’s than with Coumadin Therapy (Chest, 2021) [MEDLINE]
On the Basis of Patients with Atrial Fibrillation, Gastrointestinal Bleeding May Be Higher with Dabigatran, Edoxaban, and Rivaroxaban than with Coumadin Therapy, Although This Has Not Been Seen in Patients with Venous Thromboembolism (Chest, 2021) [MEDLINE]
However, on the Basis of Indirect Comparisons and Studies Reporting on DOAC’s for the Treatment of Cancer-Associated Thrombosis, the Risk of Bleeding May Be Lower with Apixaban than with Other DOAC’s (Chest, 2021) [MEDLINE]
Specific Reversal Agents for DOAC’s Have Been Approved (Yet Even Before the Availability of These, the Risk that a Major Bleed Will Be Fatal Appears to Be No Higher for DOAC’s than for Coumadin Therapy) (Chest, 2021) [MEDLINE]
In Patients with Venous Thromboembolism and Cancer (Cancer-Associated Thrombosis, There is a Higher Risk for Recurrence as Well as a Higher Risk for Major Bleeding than in Patients with Venous Thromboembolism without Cancer (Chest, 2021) [MEDLINE]
Systematic Review and Meta-Analysis of Treatment of Venous Thromboembolism in Patients with Cancer (Lancet Oncol, 2008) [MEDLINE]
Long-Term Full-Dose Low Molecular Weight Heparin is More Effective than Coumadin in the Secondary Prophylaxis of Venous Thromboembolism in Patients with Cancer of Any Stage, Performance Status, or Prognosis
Optimum Treatment Duration is Unclear, But Because the Prothrombotic Tendency Will Persist in Patients with Advanced Cancer, Indefinite Treatment is Generally Recommended
Unblinded, Comparative Effectiveness, Noninferiority Randomized CANVAS Trial of Direct Oral Anticoagulants vs Low Molecular Weight Heparin in Patients with Diagnosis of New Venous Thromboembolism and Cancer (JAMA, 2023) [MEDLINE]: n = 638 (from 67 oncology practices in the US)
Rates of Recurrent Venous Thromboembolism were 6.1% in the Direct Oral Anticoagulant Group and 8.8% in the Low Molecular Weight Heparin Group (Difference -2.7%; 1-sided 95% CI: -100% to 0.7%) Consistent with the Prespecified Noninferiority Criterion
Of the 6 Prespecified Secondary Outcomes, None were Statistically Significant
Major Bleeding Occurred in 5.2% of Participants in the Direct Oral Anticoagulant Group and 5.6% in the Low Molecular Weight Heparin Group (Difference -0.4%; 1-sided 95% CI: -100% to 2.5%) and Did Not Meet the Noninferiority Criterion
Severe Adverse Events Occurred in 33.8% of Participants in the Direct Oral Anticoagulant Group and 35.1% in the Low Molecular Weight Heparin Group
The Most Common Serious Adverse Events were Anemia and Death
Recommendations (American Society of Hematology Guidelines for the Management of Venous Thromboembolism, 2020) (Blood Adv, 2020) [MEDLINE]
For Patients with Venous Thromboembolism, Use of Direct Oral Anticoagulants (DOAC’s) is Recommended Over Coumadin (Conditional Recommendation, Moderate Certainty in the Evidence)
This Recommendation May Not Apply to Patients with the Following
For Patients with Venous Thromboembolism, There is No Recommendation of One DOAC Over Another (Conditional Recommendation, Very Low Certainty in the Evidence)
Factors Which May Influence the Selection of a Specific DOAC
Cancer
Concomitant Medications (Need for a Concomitant Drug Metabolized Through the CYP3A4 Enzyme or P-Glycoprotein)
Once vs Twice Daily Dosing
Out-of-Pocket Cost
Renal Function
Requirement for Lead-In Parenteral Anticoagulation
In Patients with Venous Thromboembolism (Lower Extremity Deep Venous Thrombosis or Acute Pulmonary Embolism) in the Setting of Cancer (Cancer-Associated Thrombosis), Oral Xa Inhibitors (Apixaban, Edoxaban, Rivaroxaban) are Recommended Over Low Molecular Weight Heparin for the Initiation and Treatment Phases of Anticoagulant Therapy (Strong Recommendation, Moderate-Certainty Evidence)
Edoxaban and Rivaroxaban Appear to Be Associated with a Higher Risk of Gastrointestinal Major Bleeding than Low Molecular Weight Heparins in Patients with Cancer-Associated Thrombosis and a Luminal Gastrointestinal Malignancy, While Apixaban Does Not
Consequently, Apixaban or Low Molecular Weight Heparins May Be the Preferred Options in Patients with Luminal Gastrointestinal Malignancies
Duration of Anticoagulation
General Comments
Subgroups of Patients with Venous Thromboembolism (Chest, 2021) [MEDLINE]
Venous Thromboembolism Provoked by Surgery (a Major Transient Risk Factor): 3% recurrence rate at 5 yrs
Venous Thromboembolism Provoked by a Nonsurgical Transient Risk Factor (Estrogen Therapy, Pregnancy, Leg Injury, Flight of >8 hrs): 15% recurrence rate at 5 yrs
Unprovoked (Idiopathic) Venous Thromboembolism (Not Meeting Criteria for Provocation by a Transient Risk Factor or by Cancer): 30% recurrence rate at 5 yrs
Recommendations (American Society of Hematology Guidelines for the Management of Venous Thromboembolism, 2020) (Blood Adv, 2020) [MEDLINE]
For Primary Treatment of Patients with Venous Thromboembolism (Whether Provoked by a Transient Risk Factor or by a Chronic Risk Factor or Unprovoked, Use of a Shorter Course of Anticoagulation for Primary Treatment (3-6 mos) is Recommended Over a Longer Course of Anticoagulation for Primary Treatment (6-12 mos) (Conditional Recommendations, Moderate Certainty in the Evidence
These Recommendations are Intended to Address the Duration of Primary Anticoagulant Treatment for All Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism, Defined as the Minimal Length of Time for Treatment of the Initial Venous Thromboembolism
Most Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Provoked by Temporary Risk Factors Will Discontinue Anticoagulant Therapy After Completion of the Primary Treatment
In Contrast, Many Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Provoked by Chronic Risk Factors, as Well as Patients with Unprovoked Deep Venous Thrombosis and/or Acute Pulmonary Embolism, May Continue Anticoagulant Therapy Indefinitely for Secondary Prevention After Completion of the Primary Treatment
However, if Patient and Clinician Decides to Stop Anticoagulation, Use of a Longer Course of Primary Anticoagulant Therapy (6-12 mos) is Not Recommended
For Selected Patients with a Chronic Risk Factor for Which Some Improvement is Expected Over Time (Due to Improved Mobility with Rehabilitation, etc), a Longer Course of Anticoagulation for the Primary Treatment Phase (6-12 mos) Could Be Justified
For Patients with Unprovoked Deep Venous Thrombosis and/or Acute Pulmonary Embolism, Routine Use of Prognostic Scores, D-Dimer Testing, or Ultrasound to Detect Residual Vein Thrombosis are Not Recommended to Guide the Duration of Anticoagulation (Conditional Recommendations, Very Low Certainty in the Evidence)
Indefinite Anticoagulation is Probably Appropriate for the Majority of Patients with Unprovoked Venous Thromboembolism
However, in Certain Circumstances, Such as When Patients are Undecided or the Balance Between Risks and Benefits is Uncertain, Clinicians and Patients May Use Prognostic Scores, D-Dimer Testing, or Ultrasound Assessment for Residual Thrombosis from an Initial Deep Venous Thrombosis to Aid in Reaching a Final Decision
After Completion of Primary Treatment of Deep Venous Thrombosis and/or Acute Pulmonary Embolism Provoked by a Chronic Risk Factor, Indefinite Antithrombotic Therapy is Recommended Over Stopping Anticoagulation (Conditional Recommendation, Moderate Certainty in the Evidence)
Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Provoked by a Transient Risk Factor Typically Do Not Require Antithrombotic Therapy after Completion of Primary Treatment
This Recommendation Refers to Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Provoked by a Chronic Persistent Risk Factor
However, This Recommendation Does Not Apply to Patients Who Have a High Risk for Bleeding Complications
After Completion of Primary Treatment for Patients with Unprovoked Deep Venous Thrombosis and/or Acute Pulmonary Embolism, Indefinite Antithrombotic Therapy is Recommended Over Stopping Anticoagulation (Conditional Recommendation, Moderate Certainty in the Evidence)
This Recommendation Does Not Apply to Patients Who Have a High Risk for Bleeding Complications
For Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Who Have Completed Primary Treatment and Will Continue to Receive Secondary Prevention, the Use of Anticoagulation is Recommended Over Aspirin (Conditional Recommendation, Moderate Certainty in the Evidence)
For Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Who Have Completed Primary Treatment and Will Continue Coumadin as Secondary Prevention, the Use of International Normalized Ratio (INR) Range of 2-3 is Recommended Over a Lower INR Range (1.5-1.9) (Strong Recommendation, Moderate Certainty in the Evidence)
For Patients with Deep Venous Thrombosis and/or Acute Pulmonary Embolism Who Have Completed Primary Treatment and Will Continue with a DOAC for Secondary Prevention, Use of Either a Standard-Dose DOAC or a Lower-Dose DOAC is Recommended (Conditional Recommendation, Moderate Certainty in the Evidence)
Lower-Dose DOAC Regimens Which May Be Considered for Patients Who Have Completed Primary Treatment and Will Continue with a DOAC Include the Following
In Patients with Acute Venous Thromboembolism Who Do Not Have a Contraindication, a 3 Month Treatment Phase of Anticoagulation is Recommended (Strong Recommendation, Moderate-Certainty Evidence)
Upon Completion of the 3 Month Treatment Phase of Therapy, All Patients Should Be Assessed for Extended-Phase Therapy
In Patients with Venous Thromboembolism Diagnosed in the Setting of a Major Transient Risk Factor, Extended-Phase Anticoagulation is Not Recommended (Strong Recommendation, Moderate-Certainty Evidence)
Confinement to Bed in Hospital (Only “Bathroom Privileges”) for ≥3 Days with an Acute Illness
Surgery with General Anesthesia for >30 min
In Patients with Venous Thromboembolism Diagnosed in the Setting of a Minor Transient Risk Factor, Extended-Phase Anticoagulation is Not Recommended (Weak Recommendation, Moderate-Certainty Evidence)
Minor Transient Risk Factors
Admission to Hospital for <3 Days with an Acute Illness
Confinement to Bed Out of Hospital for ≥3 Days with an Acute Illness
Leg Injury Associated with Reduced Mobility for ≥3 Days
In Patients with Venous Thromboembolism Diagnosed in the Absence of Transient Provocation (Unprovoked Venous Thromboembolism or Provoked by Persistent Risk Factor), Extended-Phase Anticoagulation with a DOAC is Recommended (Strong Recommendation, Moderate-Certainty Evidence)
In Patients with Venous Thromboembolism Diagnosed in the Absence of Transient Risk Factor (Unprovoked Venous Thromboembolism or Provoked by a Persistent Risk Factor) Who Cannot Receive a DOAC, Extended-Phase Anticoagulation with Coumadin is Recommended (Weak Recommendation, Moderate-Certainty Evidence)
The Recommendation to Offer Extended-Phase Anticoagulation Would Not Automatically Imply that All Patients with Unprovoked Venous Thromboembolism Receive Extended Therapy
Patient Preference and Predicted Risk of Recurrent Venous Thromboembolism or Bleeding Should Also Influence the Decision to Proceed with, or Continue, Extended-Phase Anticoagulation Therapy
Patients Who Receive Extended-Phase Anticoagulation Should Have This Decision Reevaluated at Least Annually, and at Times of Significant Change in Health Status
Extended-Phase anticoagulation Does Not Have a Predefined Stop Date
However, Studies of Extended-Phase anticoagulation Monitored Patients for Durations of About 2-4 yrs
Although Most Patients in These Studies Did Not Stop Anticoagulation Therapy at the End of Follow-Up, the Risk-to-Benefit Balance of Continuing Extended Anticoagulation Therapy Beyond THis Time is Uncertain
In Patients Offered Extended-Phase Anticoagulation, Use of Reduced-Dose Apixaban (2.5 mg BID) or Rivaroxaban (10 mg qday) is Recommended Over Full-Dose Apixaban or Rivaroxaban (Weak Recommendation, Very Low-Certainty Evidence)
In Patients Offered Extended-Phase Anticoagulation, Reduced-Dose DOAC (Apixaban 2.5 mg BID or Rivaroxaban 10 mg qday) is Recommended Over Aspirin or No Therapy (Strong Recommendation, Low-Certainty Evidence) and Rivaroxaban is Recommended Over Aspirin (Weak Recommendation, Moderate-Certainty Evidence)
Rivaroxaban is the Only DOAC to Be Directly Compared to Aspirin for Secondary Prevention of Venous Thromboembolism
Several Other DOACs, as Well as Coumadin, are Also Acceptable for Secondary Prevention (Extended-Phase Therapy) After Venous Thromboembolism
In Patients with an Unprovoked Proximal Deep Venous Thrombosis or Acute Pulmonary Embolism Who are Stopping Anticoagulation and Do Not Have a Contraindication to Aspirin, Aspirin is Recommended Over No Aspirin to Prevent Recurrent Venous Thromboembolism (Weak Recommendation, Low-Certainty Evidence)
Because Aspirin Has Been Shown to Be Much Less Effective at Preventing Recurrent Venous Thromboembolism than Anticoagulants, and Because Some Anticoagulants Confer a Similar Risk of Bleeding to Aspirin, We Do Not Consider Aspirin a Reasonable Alternative to Anticoagulation in Patients Who Want Extended Therapy
However, if a Patient Has Decided to Stop Anticoagulation, Prevention of Recurrent Venous Thromboembolism is One of the Benefits of Aspirin Which Needs to Be Balanced Against Aspirin’s Risk of Bleeding and Inconvenience
Use of Aspirin Should Also Be Reevaluated
Treatment of Acute Pulmonary Embolism with Hypotension (i.e. High-Risk or “Massive” Acute Pulmonary Embolism)
Therapeutic Choices
Systemic Thrombolytic Therapy
Systemic Thrombolytic Therapy Accelerates Resolution of Pulmonary Embolism (with More Rapid Lowering of Pulmonary Artery Pressure, Improved Hypoxemia, and Resolution of Perfusion Scan Defects)
However, Systemic Thrombolytic Therapy Also Increases the Risk of Hemorrhage
Catheter-Based (Mechanical-Only) Techniques for Thrombus Removal Involve Fragmentation of the Thrombus Using Various Types of Catheters (Some of Which are Designed for this Purpose)
Thrombus Fragmentation Results in Distal Displacement of the Thrombus with/without Suctioning and Removal of Some of the Thrombus Through the Catheter
Catheter-Directed Thrombolysis Uses Approximately 33% of the Dose of Thrombolytic That Systemic Thrombolysis Uses (Lowering the Risk of Hemorrhage in Brain, Gastrointestinal Trac, etc)
Catheter-Directed Thrombolysis Achieves Higher Local Concentrations of Thrombolytics at the Site of the Pulmonary Embolism and Also Facilitates Thrombus Fragmentation and Permeability Via the Catheter
Systematic Review of Venoarterial Extracorporeal Membrane Oxygenation in Massive Acute Pulmonary Embolism (Crit Care Med, 2021) [MEDLINE]
Venoarterial Extracorporeal Membrane Oxygenation Has an Emerging Role in the Management of Massive Acute Pulmonary Embolism-Related Cardiac Arrest with 61% Survival
Systemic Thrombolysis Preceding Venoarterial Extracorporeal Membrane Oxygenation Did Not Confer a Statistically Significant Increase in the Risk of Death, Yet Age >65 y/o and Cannulation During Cardiopulmonary Resuscitation were Associated with a 3-Fold and 6-Fold Risks of Death, Respectively
Absolute Contraindications to Systemic Thrombolytic Therapy (Chest Antithrombotic Therapy and Prevention of Thrombosis 2012 Guidelines) [MEDLINE]
History of Ischemic Cerebrovascular Accident (CVA) within Last 3 mos (Excluding Cerebrovascular Accident within the Last 3-4.5 hrs) (see Ischemic Cerebrovascular Accident)
Malignant Intracranial Neoplasm
History of Traumatic Brain Injury (TBI)/Facial Trauma within Last 3 mos (see Traumatic Brain Injury)
Severe Uncontrolled Hypertension on Presentation (Systolic BP >180 mm Hg, Diastolic BP >100 mm Hg)
Traumatic/Prolonged (>10 min) Cardiopulmonary Resuscitation (CPR) within Last 3 wks (see Cardiopulmonary Resuscitation)
For Streptokinase/Anistreplase, Prior Exposure (>5 Days Prior) or Prior Allergic Reaction to these Agents
Clinical Efficacy of Systemic Thrombolysis in Acute Pulmonary Embolism
Meta-Analysis of Thrombolysis in Acute PE (JAMA, 2014) [MEDLINE]: meta-analysis (16 trials, n = 2115)
Thrombolysis Decreased the Mortality Rate (2.17%), as Compared to Anticoagulation Alone (3.89%)
No Mortality Benefit was Observed in Patients >65 y/o, a Population in Whom the Risk of Hemorrhage was the Greatest
Thrombolysis Decreased the Risk of Recurrent PE (1.17%) as Compared to Anticoagulation Alone (3.04%)
Thrombolysis Increased the Risk of Major Hemorrhage (9.2%), as Compared to Anticoagulation Alone (3.4%)
No Significant Difference in Major Hemorrhage in Patients ≤65 y/o
Thrombolysis Increased the Risk of Intracranial Hemorrhage (1.5%), as Compared to Anticoagulation Alone (0.2%)
PEITHO Randomized Controlled Trial of Tenecteplase Thrombolysis (30-50 mg) in Normotensive Intermediate-Risk Pulmonary Embolism (Right Ventricular Dysfunction on Echocardiogram or CT PA Angiogram, Elevated Serum Troponin) (NEJM, 2014) [MEDLINE]: n = 1006 (mean age: 66.15 y/o; SD: 15.29)
Intention-to-Treat Analysis
Tenecteplase Thrombolysis Decreased Hemodynamic Decompensation/Death (2.6%), as Compared to Placebo Group (Anticoagulation Alone) (5.6%) (Odds Ratio 0.44; 95% CI: 0.23–0.87; P = 0.02)
Tenecteplase Thrombolysis (1.2%) Had No Impact on 7-Day Mortality Rate, as Compared to Placebo Group (Anticoagulation Alone) (1.8%) (P = 0.42)
Tenecteplase Thrombolysis (2.4%) Had No Impact on 30-Day Mortality Rate, as Compared to Placebo Group (Anticoagulation Alone) (3.2%) (P = 0.42)
Extracranial Bleeding Occurred in 6.3% in the Tenecteplase Group vs 1.2% in the Placebo Group (P < 0.001)
Stroke Occurred in 2.4% in the Tenecteplase Group (Hemorrhagic in 10 Patients vs 0.2% in the Placebo Group (Hemorrhagic in 1 That One Patient) (P = 0.003)
Mean Time Between Randomization and Death/Hemodynamic Compensation was 1.79 ± 1.6 Days in the Heparin Only (Placebo) Arm
Therefore, in Patients with Intermediate Risk Acute Pulmonary Embolism, Anticoagulation with Unfractionated Heparin/Low Molecular Weight Heparin for 2-3 Days Seems Reasonable Before Switching to Oral Anticoagulation (Eur Heart J, 2020) [MEDLINE]
Clinical Efficacy of Catheter-Directed Therapy in Acute Pulmonary Embolism
Catheter-Based Thrombus Removal Without Thrombolytic Therapy (Suction Thrombectomy)
Percutaneous Mechanical Thrombectomy with the FlowTriever System was Safe and Effective in Patients with Acute Intermediate-Risk Pulmonary Embolism, with Significant Improvement in RV/LV Ratio and Minimal Major Bleeding
Indigo
EXTRACT PE Trial (JACC Cardiovasc Interv, 2021) [MEDLINE]
In this Prospective, Multicenter Study, the Indigo Aspiration System was Associated with a Significant Reduction in the RV/LV Ratio and a Low Major Adverse Event Rate in Submassive Pulmonary Embolism
Intraprocedural Thrombolytic Drugs were Avoided in 98.3% of Patients
Catheter-Directed Thrombolysis
EKOSonic
ULTIMA Randomized Trial of Ultrasound-Assisted Catheter-Directed Thrombolysis in Acute Pulmonary Embolism (Circulation, 2014) [MEDLINE]:
In Intermediate Risk Patients, Catheter-Directed Thrombolysis was Superior to Anticoagulation Alone in Reversing Right Ventricular Dilatation at 24 hrs (With No Increase in Risk of Bleeding Complications)
SEATTLE II Trial (JACC Cardiovasc Interv, 2015) [MEDLINE]
Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis Decreased RV Dilation, Reduced Pulmonary Hypertension, Decreased Anatomic Thrombus Burden, and Minimized Intracranial Hemorrhage in Patients with Acute Massive and Submassive Pulmonary Embolism
Treatment with Using a Ultrasound Catheter-Directed Thrombolysis with Shorter Delivery Duration and Lower-Dose tPA was Associated with Improved Right Ventricular Function and Reduced Clot Burden, as Compared with baseline
Major Bleeding Rate was Low, But One Intracranial Hemorrhage Event Did Occur
Systematic Review and Meta-Analysis Comparing Catheter-Directed Thrombolysis, Systemic Thrombolysis, and Anticoagulation in the Treatment of Intermediate Risk or High Risk Pulmonary Embolism (CMAJ, 2023) [MEDLINE]: n = 20,006 (44 studies)
Compared with Systemic Thrombolysis, Catheter-Directed Thrombolysis was Associated with Decreased Mortality Rate (Odds Ratio 0.43; 95% CI: 0.32-0.57), Intracerebral Hemorrhage (Odds Ratio 0.44; 95% CI 0.29-0.64), Major Bleeding (Odds Ratio 0.61; 95% CI 0.53-0.70), and Blood Transfusion (Odds Ratio 0.46; 95% CI 0.28-0.77)
No Difference in Minor Bleeding was Observed Between the 2 Therapeutic Options (Odds Ratio 1.11; 95% CI 0.66-1.87)
Compared with Anticoagulation, Catheter-Directed Thrombolysis was Associated with Decreased Mortality Rate (Odds Ratio 0.36; 95% CI 0.25-0.52), with No Increased Risk of Intracerebral Hemorrhage (Odds Ratio 1.33; 95% CI 0.63-2.79) or Major Bleeding (Odds Ratio 1.24; 95% CI 0.88-1.75)
Conclusions
With Moderate Certainty of Evidence, the Mortality Rate and Major Bleeding Complications were Lower with Catheter-Directed Thrombolysis than with Systemic Thrombolysis
With Moderate Certainty of Evidence, as Compared to Anticoagulation, Catheter-Directed Thrombolysis was Associated with a Probable Lower Mortality Rate and a Similar Risk of Intracerebral Hemorrhage
These Findings are Largely Based on Observational Data
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]
High-Risk Acute Pulmonary Embolism (Characterized by Hemodynamic Instability)
In Suspected High-Risk Acute Pulmonary Embolism, Intravenous Anticoagulation with Unfractionated Heparin (Including Weight-Adjusted Bolus) is Recommended without Delay (Class I, Level C)
Systemic Thrombolytic Therapy is Recommended (Class I, Level B)
In Patients in Whom Thrombolysis is Contraindicated or Has Failed, Surgical Pulmonary Embolectomy is Recommended (Class I, Level C)
In Patients in Whom Thrombolysis is Contraindicated or Has Failed, Percutaneous Catheter-Directed Treatment Should Be Considered (Class IIa, Level C)
Norepinephrine and/or Dobutamine Should Be Considered (Class IIa, Level C)
In Patients with Refractory Circulatory Collapse or Cardiac Arrest, Venoarterial Extracorporeal Membrane Oxygenation (VA-ECMO) May Be Considered, in Combination with Surgical Embolectomy or Catheter-Directed Treatment (Class IIb, Level C)
In Patients with Hemodynamic Deterioration on Anticoagulation Treatment, Rescue Thrombolytic Therapy (Class I, Level B) or Alternatively, Surgical Embolectomy or Percutaneous Catheter-Directed Treatment (Class IIa, Level C), are Recommended
Recommendations for Systemic Thrombolysis (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
Consider Full-Dose Systemic Thrombolytics in the Following Groups
High-Risk Acute Pulmonary Embolism without Contraindications to Systemic Thrombolytics
Consider Reduced-Dose Systemic Thrombolytics in the Following Groups
High-Risk Acute Pulmonary Embolism with Relative Contraindications to Thrombolysis
Selected Intermediate to High-Risk Acute Pulmonary Embolism with Evidence of or Risk of Clinical Deterioration Based on Vital Signs, Severity of Right Ventricular Dysfunction, Tissue Perfusion, and/or Gas Exchange, and Presence of Low Bleeding Risk
Consider Systemic Thrombolytics in Patients with Cardiac Arrest and Suspected Acute Pulmonary Embolism
Consider Systemic Thrombolytics in Selected Patients with Intermediate or High-Risk Acute Pulmonary Embolism with Thrombus-in-Transit
Recommendations for Catheter-Directed Therapy (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
Consider Catheter-Directed Thrombolysis in the Following Groups
Intermediate to High-Risk Acute Pulmonary Embolism with Risk for Clinical Deterioration Based on Vital Signs, Severity of Right Ventricular Dysfunction, Tissue Perfusion, and/or Gas Exchange, and without Absolute Contraindication to Thrombolysis
High-Risk Acute Pulmonary Embolism with Relative Contraindications to Systemic Thrombolysis<
Consider Catheter Embolectomy in the Following Groups
Intermediate to High-Risk Acute Pulmonary Embolism with Risk for Clinical Deterioration Based on Vital Signs, Severity of Right Ventricular Dysfunction, Tissue Perfusion, and/or Gas Exchange, with Absolute or Relative Contraindications to Thrombolysis
High-Risk Acute Pulmonary Embolism with Absolute Contraindications to Systemic Thrombolysis
After Failed Systemic Thrombolysis or Catheter-Directed Thrombolysis
Thrombus-in-Transit in the Right Atrium or Right Ventricle (AngioVac System)
Recommendations for Surgical Embolectomy (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
High-Risk Acute Pulmonary Embolism with Contraindications to, or Failure of Systemic Thrombolysis or Catheter-Directed Thrombolysis
Intermediate to High Risk Acute Pulmonary Embolism, with Contraindications to, or Failure of Systemic Thrombolysis or Catheter-Directed Thrombolysis, with Risk for Clinical Deterioration Based on Vital Signs, Severity of Right Ventricular Dysfunction, Tissue Perfusion, and/or Gas Exchange
Right Heart Thrombi, Especially with Large Thromboembolic Burden
Thrombus-in-Transit Across a Patent Foramen Ovale (PFO)
Recommendations for Mechanical Hemodynamic Support (Consensus Practice from the PERT Consortium, 2019) (Clin Appl Thromb Hemost, 2019) [MEDLINE]
Consider Mechanical Mechanical Hemodynamic Support in High-Risk Acute Pulmonary Embolism with Cardiac Arrest, Refractory Shock, and/or Contraindications to or Failure of Systemic Thrombolysis
Recommendations (American Society of Hematology Guidelines for the Management of Venous Thromboembolism, 2020) (Blood Adv, 2020) [MEDLINE]
For Patients with Acute Pulmonary Embolism and Hemodynamic Compromise, Use of Thrombolytic Therapy Followed by Anticoagulation is Recommended Over Anticoagulation Alone (Strong Recommendation, Low Certainty in the Evidence
In this Case, the High Mortality of Patients with Acute Pulmonary Embolism and Hemodynamic Compromise, as Well as the Potential Lifesaving Effect of Thrombolytics, Warranted a Strong Recommendation
For Patients with Acute Pulmonary Embolism with Echocardiography and/or Biomarkers Compatible with Right Ventricular Dysfunction But without Hemodynamic Compromise (Submassive Pulmonary Embolism), Anticoagulation Alone is Recommended Over the Routine Use of Thrombolysis in Addition to Anticoagulation (Conditional Recommendation, Low Certainty in the Evidence
Thrombolysis is Reasonable to Consider for Submassive Pulmonary Embolism and Low Risk for Bleeding in Selected Younger Patients or for Patients at High Risk for Decompensation Due to Concomitant Cardiopulmonary Disease
Patients with Submassive Pulmonary Embolism Should Be Monitored Closely for the Development of Hemodynamic Compromise
For Patients with Acute Pulmonary Embolism in Whom Thrombolysis is Considered Appropriate, Use of Systemic Thrombolysis is Recommended Over Catheter-Directed Thrombolysis (Conditional Recommendation, Very Low Certainty in the Evidence)
This Recommendation Reflects Uncertainty About Catheter-Directed Thrombolysis for Acute Pulmonary Embolism Rooted in the Paucity of Randomized Trial Data and Variability in Procedural Experience Across Centers
In Centers with the Appropriate Infrastructure, Clinical Staff, and Procedural Experience, Catheter-Directed Thrombolysis May Be an Alternative to Systemic Thrombolysis, Especially for Patients with an Intermediate to High Risk for Bleeding, Because the Total Dose and Duration of Administration of Thrombolytic Agents are Lower When Delivered by Catheter
In Patients with Acute Pulmonary Embolism Associated with Hypotension (Systolic Blood Pressure <90 mm Hg) Who Do Not Have a High Bleeding Risk, Systemic Thrombolytic Therapy is Recommended (Weak Recommendation, Low-Certainty Evidence)
Studies of Systemically Administered Thrombolytic Therapy Have Utilized Different Agents at Varying Doses
Due to Lack of Comparative Data Between These Approaches, No Agent/Dosing Strategy is Favored Over Another
In Most Patients with Acute Pulmonary Embolism Which is Not Associated with Hypotension, Systemic Thrombolytic Therapy is Not Recommended (Strong Recommendation, Low-Certainty Evidence
In Selected Patients with Acute Pulmonary Embolism Who Clinically Deteriorate After Starting Anticoagulation But Have Yet to Develop Hypotension and Who Have an Acceptable Bleeding Risk, Systemically Administered Thrombolytic Therapy is Recommended (Weak Recommendation, Low-Certainty Evidence)
Deterioration (Which Has Not Resulted in Hypotension) May Include Any of the Following
Progressive Tachycardia
Decrease in Systolic Blood Pressure (But Remains >90 mm Hg)
Increase in Jugular Venous Pressure
Worsening Gas Exchange
Signs of Shock (Cold Sweaty Skin, Reduced Urine Output, Confusion)
Progressive Right Heart Dysfunction (on Echocardiogram)
Increase in Cardiac Biomarkers
In Patients with Acute Pulmonary Embolism Who are Treated with a Thrombolytic Agent, Systemic Thrombolytic Therapy Using a Peripheral Vein is Recommended Over Catheter-Directed Thrombolysis (Weak Recommendation, Low-Certainty Evidence)
No Randomized Trials or Observational Studies Have Compared Contemporary Catheter-Assisted Thrombus Removal with Systemic Thrombolytic Therapy
In Patients with Acute Pulmonary Embolism Associated with Hypotension Who Also Have High Bleeding Risk, Failed Systemic Thrombolysis, or Shock Which is Likely to Cause Death Before Systemic Thrombolysis Can Take Effect (within Hours), if Appropriate Expertise and Resources are Available, Catheter-Directed Therapy is Suggested (Weak Recommendation, Low-Certainty Evidence)
Treatment of Thrombus in Transit (Clot in Transit)
General Comments
Thrombus in Transit May Be Found in the Inferior Vena Cava, Right Atrium, or Right Ventricle (Circulation, 2019) [MEDLINE]
Thrombus in Transit Accounts for a 5-Fold Increase in Death Resulting from Acute Pulmonary Embolism
Thrombus in Transit is Usually Identified on CT PA Angiogram or Echocardiogram (May Appear as Either Adherent or Free-Floating)
Thrombus in Transit is Present in 4% of Patients with Acute Pulmonary Embolism
Clinical Efficacy
Observational Pooled Analysis of the Treatment of Thrombus in Transit (Vasc Med, 2015) [MEDLINE]: n = 328
Thrombolysis (Odds Ratio 4.8; 95% CI: 1.5–15.4) and Surgical Embolectomy (Odds Ratio 2.6; 95% CI: 0.9–7.6]) were More Often Associated with a Favorable Outcome than Anticoagulation Alone
Study of Treatment of Thrombus in Transit (Am J Med, 2017) [MEDLINE]: n = 255 treated with anticoagulation, n = 70 treated with reperfusion
Comparing Anticoagulation with Reperfusion, There was No Difference in All-Cause Mortality (6.2% vs 14%; P = 0.15) or Pulmonary Embolism-Related Mortality (4.7% vs 7.8%; P = 0.47)
Analysis of Risk Factors for Pulmonary Embolism with Clot in Transit (Thromb Res, 2020) [MEDLINE]: n = 57
Clot in Transit was Present in 8.6% of Patients Who Had an Echocardiogram
Multivariate Analysis Demonstrated Heart Failure (OR 2.8; 95% CI: 1.2-6.5, P = 0.01), a Pre-existing Central Venous Catheter (OR 2.5; 95% CI: 1.1-5.7, P = 0.03), and Hypotension (OR 2.1; 95% CI: 1.1-3.7, P = 0.02) to Be Independently Associated with Clot in Transit
All-Cause Mortality by 7 Days was Higher in Clot in Transit Patients (12.5% vs 5.1%, P = 0.02)
Clot in Transit Patients Who Died were More Likely to Have Presented with Hemodynamic Collapse (57.1% vs 14.0%, P = 0.02), Mental Status Change (100% vs 22.0%, P < 0.001), and to Be Intubated (100% vs 36.0%, P = 0.001)
Review of Considerations in the Setting of Pulmonary Embolism with Clot in Transit (Crit Care Clin, 2020) [MEDLINE]
Clot in Transit is Believed to Be Associated with High Mortality
Case Series of 3 Cases of Catheter-Directed Embolectomy (with Inari FlowTriever) for Right Atrial Clot in Transit (Catheter Cardiovasc Interv, 2021) [MEDLINE]
All of the Patients Had Contraindications to Surgical Thrombo-Embolectomy and Thrombolytic Therapy
Successful Catheter-Based Thrombo-Embolectomy Can Be Perfomed in High-Risk Patients with Right Arial Clot in Transit with or without Acute Pulmonary Embolism
Review of Endovascular Therapies for Clot in Transit (Semin Intervent Radiol, 2022) [MEDLINE]
Review of the Current Endovascular Devices for the Treatment of Right Heart Thrombus and Clot in Transit
Treatment of Asymptomatic Acute Pulmonary Embolism (PE)
Rationale
Asymptomatic Pulmonary Embolism is Diagnosed in About 1% of Outpatients and About 4% of Inpatients Who Have Contrast-Enhanced Chest CT Scans (Chest, 2021) [MEDLINE]
Most Asymptomatic Pulmonary Emboli are Found in Patients with Known Malignancy and are Reported on CT Scans Which Have Been Obtained for Another Indication (Such as Cancer Staging, Surveillance, or Treatment Response Evaluation) (Chest, 2021) [MEDLINE]
About 50% Involve the Lobar or More Central Pulmonary Arteries, While the Remaining 50% Involve More Distal Pulmonary Arteries (Chest, 2021) [MEDLINE]
In Patients Who are Incidentally Found to Have Asymptomatic Pulmonary Embolism, the Standard Initiation and Treatment with Anticoagulation is Recommended, as for Patients with Symptomatic Acute Pulmonary Embolism (Weak Recommendation, Moderate-Certainty Evidence)
Treatment of Acute Subsegmental Pulmonary Embolism (PE)
Rationale/Background
Improvements in Computed Tomography (CT Angiography) Have Led to Increased Diagnosis of Subsegmental Pulmonary Emboli
Subsegmental Pulmonary Emboli Have Increased from Approximately 5% to >10% of All Detected Pulmonary Emboli
Due to Small Size of Subsegmental Pulmonary Emboli, They are More Likely to Be a False-Positive Finding than a Pulmonary Embolism in the Segmental/More Proximal Pulmonary Arteries
Subsgmental Pulmonary Embolism is More Likely to Be a Real Finding if the Following Features are Present
Computed Tomography (CT) Pulmonary Artery Angiogram is of High Quality with Good Opacification of the Distal Pulmonary Arteries
Presence of Multiple Intraluminal Defects
Defects Involve More Proximal (Larger) Subsegmental Arteries
Defects are Seen on >1 Image
Defects are Surrounded by Contrast, Rather than Adherent to Pulmonary Artery Walls
Defects are Seen on >1 Projection
Patient is Symptomatic (as Opposed to Pulmonary Embolism Being an Incidental Finding)
Presence of High Clinical Pretest Probability for Pulmonary Embolism
Elevated Plasma D-Dimer without Another Explanation
Since a True Subsegmental Pulmonary Embolism is Likely to Have Arisen From a Small Deep Venous Thrombosis, the Risk of Progressive or Recurrent Venous Thromboembolism Without Anticoagulation is Expected to Be Lower Than in Patients with a Larger Pulmonary Emboli
Subsequent Evaluation of Acute Subsegmental Pulmonary Embolism Should Include Lower Extremity Venous Doppler Studies to Classify the Patient According to One of the Following
Subsegmental Acute Pulmonary Embolism + No Lower Extremity Proximal Deep Venous Thrombosis + Low Risk of Recurrent Venous Thromboembolism
Factors Associated with Low Risk of Recurrent Venous Thromboembolism
Absence of Active Cancer
Normal Mobility
Outpatient Status
Presence of Reversible Risk Factor for Venous Thromboembolism (Recent Surgery, etc)
Clinical Surveillance (with Serial Lower Extremity Dopplers, etc) is Recommended Over Anticoagulation (Weak Recommendation, Low-Certainty Evidence)
Presence of High Risk of Bleeding May Favor Clinical Surveillance Strategy Over Anticoagulation
Subsegmental Acute Pulmonary Embolism + No Lower Extremity Proximal Deep Venous Thrombosis + High Risk of Recurrent Venous Thromboembolism
Factors Associated with High Risk of Recurrent Venous Thromboembolism
Active Cancer (Especially if Metastatic or on Chemotherapy)
Decreased Mobility
Hospitalization
Absence of Reversible Risk Factor for Venous Thromboembolism (Recent Surgery, etc)
Anticoagulation is Recommended Over Clinical Surveillance (Weak Recommendation, Low-Certainty Evidence)
Presence of Low Cardiopulmonary Reserve May Favor Anticoagulation Over Surveillance Strategy
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A Prospective, Single-Arm, Multicenter Trial of Ultrasound-Facilitated, Catheter-Directed, Low-Dose Fibrinolysis for Acute Massive and Submassive Pulmonary Embolism: The SEATTLE II Study. JACC Cardiovasc Interv 2015;8:1382-92 [MEDLINE]
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Thrombolytics
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Thrombus in Transit
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