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Communications to the Editor |

Clot Burden and Comorbidity in Natural History of Untreated Pulmonary Thromboembolism : Autopsy Data in the Trial by Barritt And Jordan FREE TO VIEW

Stephen Iles
Author and Funding Information

Affiliations: Bristol Royal Infirmary Bristol, UK,  *Tucson, AZ

Correspondence to: Stephen Iles, BSc, Canterbury Respiratory Research Group, Hagley Hostel, Christchurch Hospital, Christchurch, New Zealand; e-mail: steveiles@doctors.org.uk



Chest. 2003;124(3):1178-1179. doi:10.1378/chest.124.3.1178
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Published online

To the Editor:

I read with interest the special report by Dalen (November 2002),1 who discussed the mortality of untreated pulmonary thromboembolism (PE). The only prospective randomized trial2 of anticoagulants vs placebo that showed benefit in acute PE was performed at the Bristol Royal Infirmary in 1957 and published shortly thereafter. Dalen1 quotes mortality of untreated PE as 38%.

In the study by Barritt and Jordan,2 5 of 19 untreated patients died, which equates to 26% mortality, and it is unsure where the 38% quoted comes from. In addition, last year, an audit of the autopsy records of the participants enrolled in this landmark trial was conducted in order to ascertain the findings at death, as the original report was incomplete and has therefore been criticized.3 The findings are shown in Table 1 . The audit, conducted within the Department of Pathology at the Bristol Royal Infirmary, illustrate two observations about the participants enrolled in the trial by Barritt and Jordan,2 and who died with untreated PE: (1) coincidental morbidity and infection was likely to be contributory to their demise, and (2) a large amount of residual thrombus or clot burden was found both in the lung and in other venous sites with potential to embolize to the lung.

These observations should be kept in mind when deciding the cost/benefit ratio of anticoagulation in those patients identified to have small (subsegmental or less) PE with no source of potential thromboemboli and no continuing risk factors for venous thromboembolism. This difficult clinical question needs to be addressed especially in the light of rapidly improving imaging technology such as multidetector spiral CT angiography with which smaller PEs are detected.

Table Graphic Jump Location
Table 1. Autopsy Findings of the Five Patients Who Died With PE Randomized to No Anticoagulation*
* 

From the study by Barritt and Jordan.2 DVT = deep vein thrombosis.

Dalen, JE (2002) Pulmonary embolism: what have we learned since Virchow?Chest122,1801-1817. [PubMed] [CrossRef]
 
Barritt, DW, Jordan, SC Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.Lancet1960;1,1309-1312. [PubMed]
 
Wolfe, TR, Hartsell, SC Pulmonary embolism: making sense of the diagnostic evaluation.Ann Emerg Med2001;37,504-514. [PubMed]
 
To the Editor:

Dr. Iles is correct: the mortality of untreated pulmonary embolism (PE) in the small (but only) randomized clinical trial reported by Barritt and Jordan1 was five deaths among 19 patients (26%), not 38% as shown in Table 1 in my article.2 I apologize for this error. Their findings,1 coupled with the other reports of the mortality of untreated PE,36 would indicate that the mortality of untreated PE is approximately 30%. Given the fact that the mortality of PE in patients treated with heparin and warfarin is < 5%,78 it is unlikely that there will be additional randomized clinical trials comparing heparin to placebo in patients with PE, or additional reports of the mortality of untreated PE.

References
Barritt, DW, Jordan, SC Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.Lancet1960;1,1309-1312. [PubMed]
 
Dalen, JE Pulmonary embolism: what have we learned since Virchow? Treatment and prevention.Chest2002;122,1801-1817. [PubMed] [CrossRef]
 
Coon, WW, Willis, PW, Symous, MJ Assessment of anticoagulant treatment of venous thromboembolism.Am J Surg1969;170,559-567
 
Zilliacus, H On specific treatment of thrombosis and pulmonary embolism with anticoagulants.Acta Med Scand1946;171(suppl),1-221
 
Hermann, RE, Davis, JH, Holden, WD Pulmonary embolism: a clinical and pathological study with emphasis on the effect of prophylactic therapy with anticoagulants.Am J Surg1961;102,19-28. [PubMed]
 
Morrell, MT, Truelove, SC, Barr, A Pulmonary embolism.BMJ1963;2,830-835. [PubMed]
 
Carson, JL, Kelley, MA, Duff, A, et al The clinical course of pulmonary embolism.N Engl J Med1992;326,1240-1245. [PubMed]
 
Douketis, JD, Kearon, C, Bates, S, et al Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.JAMA1998;279,458-462. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Autopsy Findings of the Five Patients Who Died With PE Randomized to No Anticoagulation*
* 

From the study by Barritt and Jordan.2 DVT = deep vein thrombosis.

References

Dalen, JE (2002) Pulmonary embolism: what have we learned since Virchow?Chest122,1801-1817. [PubMed] [CrossRef]
 
Barritt, DW, Jordan, SC Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.Lancet1960;1,1309-1312. [PubMed]
 
Wolfe, TR, Hartsell, SC Pulmonary embolism: making sense of the diagnostic evaluation.Ann Emerg Med2001;37,504-514. [PubMed]
 
Barritt, DW, Jordan, SC Anticoagulant drugs in the treatment of pulmonary embolism: a controlled trial.Lancet1960;1,1309-1312. [PubMed]
 
Dalen, JE Pulmonary embolism: what have we learned since Virchow? Treatment and prevention.Chest2002;122,1801-1817. [PubMed] [CrossRef]
 
Coon, WW, Willis, PW, Symous, MJ Assessment of anticoagulant treatment of venous thromboembolism.Am J Surg1969;170,559-567
 
Zilliacus, H On specific treatment of thrombosis and pulmonary embolism with anticoagulants.Acta Med Scand1946;171(suppl),1-221
 
Hermann, RE, Davis, JH, Holden, WD Pulmonary embolism: a clinical and pathological study with emphasis on the effect of prophylactic therapy with anticoagulants.Am J Surg1961;102,19-28. [PubMed]
 
Morrell, MT, Truelove, SC, Barr, A Pulmonary embolism.BMJ1963;2,830-835. [PubMed]
 
Carson, JL, Kelley, MA, Duff, A, et al The clinical course of pulmonary embolism.N Engl J Med1992;326,1240-1245. [PubMed]
 
Douketis, JD, Kearon, C, Bates, S, et al Risk of fatal pulmonary embolism in patients with treated venous thromboembolism.JAMA1998;279,458-462. [PubMed]
 
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