Death from PE was a common finding in our analysis, accounting for 5.2% of adult necropsies at King’s College Hospital, London, UK, in the 10 year period from 1991 to 2000. In the analysis of the adult population who underwent necropsy, fatal PE was found more often in non-surgical patients than in surgical patients. Previous retrospective postmortem studies have described similar findings in medical patients.10,11
Of the 10% of deaths in hospital as a result of PE, Sandler and Martin showed that about three quarters of these occurred in patients who had not undergone a surgical procedure linked to their last illness.11
Acute infection was the most common medical illness found in patients who had died from PE, in particular patients with respiratory infection. In a postmortem study of non-surgical patients dying in the infectious diseases department of a Swedish hospital, high numbers of patients with respiratory tract infections were also found to have died from fatal PE.12
The pathophysiology of VTE in the presence of acute infection remains to be fully defined, but recent evidence suggests that respiratory viruses are capable of infecting endothelial cells and causing a shift from anticoagulant to procoagulant activity that is associated with induction of tissue factor expression.13
The association between cancer and thrombosis is well characterised and was described more than a century ago.14
Our results appear to support Trousseau’s original observations, with about one in four patients who had necropsy confirmed fatal PE suffering from cancer. These findings are in keeping with a recent clinical trial undertaken in a broad range of surgical patients,15
which used necropsy confirmed fatal PE as the primary study endpoint. An additional analysis of the primary trial findings revealed that PE was responsible for almost four times the number of deaths in patients undergoing cancer surgery compared with those undergoing comparable surgical procedures without cancer.16
Increased age closely mirrored increases in the numbers of fatal PE in our study. There were no cases of fatal PE in patients under age 18 years. Fatal PE was not common in the 3rd, 4rth, or 5th decades, but greatly increased during the 6th to 9th decades, peaking in the 9th decade. Age is accepted as an independent risk factor for VTE. The risk of thrombosis increases greatly with age, from approximately 1/10 000 people each year before the age of 40, to 1/100 each year for those aged 75 years and over.17
It has been suggested that the association between age and VTE relates to a combination of decreased mobility and muscle tone with increased morbidity and degenerative vascular changes.17
“Our study shows that pulmonary embolism is a cause of a substantial number of deaths in hospital patients, despite advances in the diagnosis and treatment of venous thromboembolic disease”
Only three patients died of PE after MI during the 10 year study period presented here. This is in contrast to a previous study for the period 1972 to 1978 in which 31% of patients with necropsy verified fatal PE had suffered a recent MI.18
The low levels of fatal PE found in our study after MI probably reflect improvements in cardiac patient care, such as rapid mobilisation, more efficient treatment of heart failure, and the provision of some form of thrombolytic, antithrombotic, and/or antiplatelet treatment.
Take home messages
- Thromboembolic events are still a relatively common cause of death in hospitalised patients, despite advances in the diagnosis and treatment of venous thromboembolic disease, and appear to occur more frequently in non-surgical than in surgical patients
- Those patients who are acutely ill, especially with an acute infectious disease or active cancer, are an obvious group to identify and target with appropriate thromboprophylaxis
Necropsy and organ retention have become a contentious issue in the UK. The issue first came to public attention with the Bristol Royal Infirmary19
and Alder Hey inquiries,20
which have resulted in the provision of strict guidelines on consent for postmortem examinations, in particular the retention of organs and tissue.21,22
It is thought that this publicity will significantly reduce the number of necropsies undertaken,23
which will limit future studies of the relation between hospitalisation, PE, and death. From a high of 71% in the period 1966 to 1970, the necropsy rate fell, particularly in the adult population, in the last three years of our study (1998–2000) to a low of 29.9%. These findings mirror closely those of the National Confidential Enquiry into Perioperative Deaths (NCEPOD). The pathology advisors to NCEPOD described a fall from 41% in 1988–1989 to 31% in 1999–2000, and note that the number of necropsies will fall even further as a result of the organ retention issues.23
In our study, the necropsy rate in children less than 18 years of age dipped considerably in 1998–1999, but returned to a higher level (79%) in 2000.
There are clear limitations to our study and also potential sources of error. Without denominator numbers for the surgical and medical patient groups, no interpretation is possible regarding the actual incidence of fatal PE. The lower number of cases of fatal PE in the surgical population could reflect a lower number of necropsies performed in deaths associated with surgical intervention. The necropsy rate was falling significantly towards the end of the 10 year study period, and this limits the strength of the conclusions that can be drawn. Because our study is retrospective it was not possible to use a uniform classification of PE. It is difficult to distinguish between fatal, contributory, and incidental emboli when the definitions and interpretations are based on pathologists’ opinions across a long time period (35 years). In an attempt to minimise the number of false positives included in our analysis, only postmortem examinations describing emboli in the main pulmonary trunk or proximal pulmonary arteries as the main cause of death are included.
Our study shows that PE is a cause of a substantial number of deaths in hospital patients, despite advances in the diagnosis and treatment of VTE. We would suggest that a fatal PE rate of 5% in adult hospital patients is unacceptably high, given the potential to prevent and treat VTE. Those patients who are acutely ill, especially with an acute infectious disease or active cancer, are an obvious group to identify and target with appropriate thromboprophylaxis, as recommended by international, national, and local guidelines. This is not happening in our hospital24
or other institutions,25,26
but would have an impact on these potentially preventable deaths.