Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?

Patients admitted to the hospital for acute exacerbation of COPD are generally regarded as being at high risk of venous thromboembolism (VTE) (prevalence 5%-29%), possibly due to the frequent coexistence of other risk factors, such as immobility, history of smoking, and venous stasis.1 The exact mechanism(s) behind this association remains poorly understood, however.

Among patients with moderate-very severe COPD (GOLD criteria stage II-IV),  high BMI, low exercise tolerance, history of pneumothorax, congestive heart failure, and peripheral vascular disease have also been associated with VTE.1

Systemic inflammation has also been implicated in increasing the risk of VTE in patients with COPD. Although the pathophysiology of COPD is largely defined by the local inflammatory response to airway injury, evidence suggests that there is also a systemic inflammatory response in COPD.2,3 This systemic inflammation could in turn contribute to the increased risk of vascular disease, including VTE, coronary artery disease, and cerebrovascular disease.4

Bonus pearl: Did you know that VTE may be 3x more prevalent among patients with COPD exacerbation without known cause (vs those with identifiable cause) and is associated with a 1-year mortality of 61.9%! 5

References:

  1. Kim V, Goel N, Gangar J, et al. Risk factors for venous thromboembolism in chronic obstructive pulmonary disease. Chronic Obstr Pulm Dis 2014;1: 239-249. https://www.ncbi.nlm.nih.gov/pubmed/25844397
  2. Lankeit M, Held M. Incidence of venous thromboembolism in COPD: linking inflammation and thrombosis? Eur Respir J 2016;47(2):369-73. https://www.ncbi.nlm.nih.gov/pubmed/26828045
  3. Sinden NJ1, Stockley RA. Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence. Thorax 2010;65:930-6. https://www.ncbi.nlm.nih.gov/pubmed/20627907
  4. King PT. Inflammation in chronic obstructive pulmonary disease and its role in cardiovascular disease and lung cancer. Clinical and Translational Medicine 2015;4:26. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518022/
  5. Gunen H, Gulbas G, In E, et al. Venous thromboemboli and exacerbations of COPD. Eur Respir J 2010;36:1243-8.  https://www.ncbi.nlm.nih.gov/pubmed/19926740 

Contributed by Camilo Campo, Medical Student, Harvard Medical School, Boston, MA.

Why are patients with acute exacerbation of COPD at higher risk of venous thromboembolism (VTE)?

Should I routinely consider the possibility of pulmonary embolism (PE) in my patients hospitalized for syncope?

Syncope is a well-known initial manifestation of pulmonary embolism (PE)1.  However, given the varied causes of syncope, determining the prevalence of PE among patients hospitalized for syncope is important.   

A multicenter prospective study2 enrolled 560 patients not already on anticoagulation who were hospitalized for a first episode syncope.  Of patients who had either a high pretest probability for PE, positive D-dimer assay or both, PE was diagnosed in 17%, or nearly 1 of 6 of enrolled patients, based on CT or ventilation/perfusion scan. PE was found more frequently among patients with syncope of undetermined cause than those with an alternative explanation (25.4% vs 12.7%). 

Another multicenter prospective study (2019), however, found a much lower prevalence of PE (0.6%) among patients evaluated in the ED for syncope, including those who were not hospitalized.3 A related commentary on the article reported a prevalence of 4.1% in the total study population, assuming a “worst-case scenario calculation.” 4 

Given these divergent results, perhaps the best advice is to consider PE as cause of syncope in the proper context and minimize over testing when suspicion remains low.

 

References 

  1. Thames MD, Alpert JS, Dalen JE. Syncope in patients with pulmonary embolism. JAMA 1977;238:2509-2511. https://www.ncbi.nlm.nih.gov/pubmed/578884
  2. Prandoni P, Lensing AWA, Prins MH, et al. Prevalence of pulmonary embolism among patients hospitalized for syncope. N Engl J Med 2016;375:1524-31. http://www.nejm.org/doi/full/10.1056/NEJMoa1602172
  3. Thiruganasambandamoorthy V, Sivilotti MLA, Rowe BH, et al. Prevalence of pulmonary embolism among emergency department patients with syncope: a multicenter prospective cohort study [published online January 25, 2019]. Ann Emerg Med. doi:10.106/j.annemergmed.2018. https://www.annemergmed.com/article/S0196-0644(18)31535-X/fulltext
  4. Anonymous. Pulmonary embolism uncommon in syncope hospitalizations. Pulmonology Advisor. February 6, 2019.  https://www.pulmonologyadvisor.com/pulmonary-embolism-uncommon-in-syncope-hospitalizations/printarticle/832069/

 

Contributed in part by Rebecca Berger  MD, Department of Medicine, Mass General Hospital, Boston, MA

If you liked this post, sign up under MENU and receive future pearls straight into your mailbox!

Should I routinely consider the possibility of pulmonary embolism (PE) in my patients hospitalized for syncope?

Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?

Although we often think of syncope caused by acute pulmonary embolism (APE) in the setting of submassive or massive APE and right ventricular failure or shock (1,2), less massive APE may potentially cause syncope as well by triggering a vaso-vagal reflex (3).

For sure, a significant association between submassive or massive APE and syncope has been reported (1,2).  More specifically, patients with syncope and APE may be more likely to have systolic blood pressure <90 mmHg, right ventricular dilation and right ventricular hypokinesis (1). Another study reported a higher rate of central embolism (83% vs 43%), right ventricular dysfunction (91% vs 68%) and troponin positivity (80% vs 39%), but not 30 day mortality (2).

In contrast, 1 study found that patients with syncope as a presenting symptom of APE did not show a more serious clinical picture (e.g. shock) than those without syncope (3), while another found EKG signs of acute right ventricle overload in only 25% of patients with syncope (4).  

So while massive APEs may be associated with syncope, they don’t seem to be a prerequisite for this condition.

References

1.  Omar HR, Mirsaeidi M, Weinstock MB, et al. Syncope on presentation is a surrogate for submassive and massive acute pulmonary embolism. Am J Emerg Med 2018;36:297-300. https://www.ncbi.nlm.nih.gov/pubmed/29146419

2. Altinsoy B, Erboy F, Tanriverdi H, et al. Syncope as a presentation of acute pulmonary embolism. Ther Clin Risk Manag 2016;12:1023-28. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930221/

3. Castelli R, Tarsia P, Tantardini G et al. Syncope in patients with pulmonary embolism: comparison between patients with syncope as the presenting symptom of pulmonary embolism and patients with pulmonary embolism without syncope. Vascular Medicine 2003;8:257-261. https://journals.sagepub.com/doi/abs/10.1191/1358863x03vm510oa

4. Miniati M, Cenci, Monti S, et al. Clinical presentation of acute pulmonary embolism: survey of 800 cases. PloS One 2012;7:e30891.

If you liked this post, sign up under MENU and receive future pearls straight into your mailbox!

 

Can syncope be related to acute pulmonary embolism in the absence of hemodynamic instability or right ventricular failure?