What are the latest recommendations for the management of venous thromboembolism?

BEEM Bottom Line

Why is this study important?

This guideline presents 9 updated and 3 new recommendations on various aspects of venous thromboembolism (VTE) including both deep venous thrombosis (DVT) and pulmonary embolism (PE).

Which, if any, threats to validity are most likely to have an impact on the results and how?

Of the 54 recommendations, 20 are based on strong evidence. The use of resource implications and patient preferences in formulating recommendations are unclear and there is relatively weak applicability to ED settings.

How do the key results compare with the current evidence?

Updates The recommendations are congruent with previous VTE guidelines although there is variable applicability to ED patients.

How should this study impact the care of ED patients?

This guideline addresses some common scenarios faced in the ED (treatment of new DVT, recurrent DVT, stable/unstable PE). The dosing of oral anticoagulants (OAC) and confounders are not directly addressed in the main paper or online supplements.

Study Summary

Pubmed ID

26867832

Reference

Kearon C, Akl EA, Ornelas J, et al. Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest. 2016 Feb;149(2):315–52.

Study Design

Clinical Practice Guideline

Population

Included: Patients with VTE disease; age, gender and other medical comorbidity modifiers are unspecified.

Excluded: None stated.

Index Tests

History and physical exam; chest x-ray; electrocardiography (ECG); NT-proBNP and BNP; echocardiography; lung US; bioimpedance.

Reference Tests

Adjudication of clinical data by independent reviewers blinded to the study’s primary index test results.

Diagnosis Interest

Acute heart failure.

Scope

Not clearly specified; presumably anyone who treats patients with VTE disease.

Key Results

N = 17,893 patients in 57 studies.

CXR = chest x-ray; LR = likelihood ratio; QUADAS = Quality Assessment of Diagnostic Accuracy Studies; Sn = sensitivity; Sp = specificity.

BEEM Critique

Key Questions and Recommendations

Key Recommendations Recommendations: Strong (Grade 1); Weak (2). Quality of Evidence: High (Grade A); Moderate (B); Weak (C). Emergency Department (ED) Relevant Recommendations

  1. Treat patients with proximal DVT or PE with anticoagulants (AC) for ≥ 3 months (1B).
    1. If no cancer, suggest start with dabigatran, a direct thrombin inhibitor (DTI), or a factor Xa Inhibitor (FXaI: apixaban, rivoroxaban or edoxaban; all 2B) instead of a vitamin K antagonist (VKA: warfarin).
    2. If cancer thrombosis, then consider a low molecular weight heparin (LMWH), a DTI or a FXaI over VKA (all 2C).
 
  1. Treat patients with AC for ≥ 3 months if VTE related to surgery (1B) or some other transient risk factor (1B).
 
  1. Treat patients with AC for ≥ 3 months for first or second proximal DVT or PE, use regardless of bleeding risk (2B).
 
  1. Consider aspirin if AC stopped to avoid recurrent VTE (2B).
 
  1. If isolated distal DVT without extension risk factors or symptoms, consider serial ultrasound (US) every 2 weeks for resolution instead of AC use (2C). If high risk for extension or severe symptoms, then treat with AC.
    1. If using serial US to follow low risk distal DVT, initiate AC use if distal extension (2C) or proximal extension (1B).
 
  1. If acute proximal DVT, may consider catheter-directed thrombolysis (CDT) if cost, comorbidity or risk of post-thrombotic syndrome (PTS) warrant CDT over AC use (2C).
 
  1. In isolated DVT of leg, use of compression stockings to prevent PTS is NOT warranted (2B).
 
  1. In patients with subsegmental PE and distal DVT with low risk of VTE recurrence, AC may be deferred for clinical surveillance (2C).
 
  1. Patients with a low-risk PE and safe home environment need not be admitted (2B).
      CARDIO-RESP (Part I) s Peripheral Vascular Disease  |  PubMed ID: 26867832
  1. In patients with PE and hypotension (sBP < 90), then patient should get thrombolysis vs. no treatment (2B).
    1. Thrombolysis not recommended if not hypotensive (1B).
    2. Patients on AC and deteriorating but not hypotensive, can receive thrombolysis if risk of bleeding risk is low (2C).
    3. Patients should receive thrombolysis through a peripheral intravenous (IV) line rather than CDT (2C).
    4. Hypotensive patients with failed thrombolysis, high bleeding risk, or impending death, warrant catheter-directed thrombectomy if resources and skilled personnel are available (2C).
 
  1. AC is recommended over thrombolysis for patients with acute upper extremity DVT (2C).
 
  1. Patients with recurrent VTE while on therapeutic OAC should be switched to LMWH temporarily (2C).
    1. Patients with recurrent VTE while compliant on long-term LMWH should have dose increased by 2,530% of original.
Risk Factors for Bleeding on AC Therapy Age > 65 years, previous bleeding, cancer (especially metastatic), renal failure, liver failure, thrombocytopenia, prior cerebral vascular accident, diabetes, anemia, antiplatelet treatment, poor AC control, reduced functional capacity, recent surgery, frequent falls, alcohol abuse, nonsteroidal anti-inflammatory drug use. 0 = low risk, 1 = mod risk, 2+ = high risk of bleeding Risk Factors for Extension of Distal DVT Positive D-dimer, extensive thrombosis > 5cm/multiple veins/> 7mm diameter, thrombus close to proximal veins, no reversible provoking factor for DVT, active cancer, prior Hx of VTE, inpatient status. Lower risk if leg DVT in muscular veins (soleus, gastrocnemius) vs. axial veins (true deep, peroneal, tibial).
Risk Factors for Bleeding on AC Therapy Risk Factors for Extension of Distal DVT
Age > 65 Positive D-dimer
Previous bleeding, Extensive thrombosis > 5cm/multiple veins/> 7mm diameter
Cancer (especially metastatic) Thrombus close to proximal veins
Renal or liver failure No reversible provoking factor for DVT
Thrombocytopenia Active cancer
Prior cerebral vascular accident Prior VTE
Diabetes Inpatient status
Anemia Lower risk if leg DVT in muscular veins (soleus, gastrocnemius)
Antiplatelet treatment No lower risk if DVT in axial veins (true deep, peroneal, tibial)
Poor AC control  
Reduced functional capacity  
Recent surgery  
Frequent falls  
Alcohol abuse  
Nonsteroidal anti-inflammatory drug use  
0 = low risk of bleeding, 1 = moderate risk of bleeding, 2+ = high risk of bleeding

Risk of Bias Assessment

Appraisers
A1 A2 A3
1 The research question is sensible and answerable. Yes Yes Yes
2 The search included all languages, databases, abstracts, bibliographies, and expert contact. No No No
3 The search for studies was unbiased and reproducible. Maybe Maybe Maybe
4 The selection of studies was unbiased and reproducible. Maybe Maybe Maybe
5 The data abstraction was unbiased (e.g., conducted independently by 2 researchers). Yes Yes Yes
6 The quality assessment of the primary studies used QUADAS, was unbiased and reproducible. Yes Yes Yes
7 The quality of the primary studies is high. Yes Yes Yes
8 The populations, cut-off thresholds, and reference standards were similar for combined studies. Yes Yes Yes
9 The subgroups were stated a priori and appropriate. Yes Yes Yes
10 The methods of meta-analyses are valid (e.g., summary ROC or bivariate random effects). Yes Yes Yes

A = appraiser; ROC = receiver operating characteristic.

Funding & Conflicts of Interest

Funding

American College of Chest Physicians.

Conflicts of Interest

Unknown.

Potential Threats to Validity

Footnotes

Contributors

Authors

Suneel Upadhye, MD, FRCP(C), MSc
Associate Professor, Division of Emergency Medicine, McMaster University, Hamilton, ON Canada

Appraisers

Worster A; de Wit K; Updahye, S.

Competing Interest Disclosure

Dr. Upadhye - No conflicts of interest (ICMJE)