A pulmonary embolism (PE) is a common disease accounting for the hospitalization or death of more than 65 000 people in Canada every year . The diagnosis of PE remains one of the most difficult problems confronting physicians. PE is considered in the differential diagnosis of many clinical presentations and in a wide variety of clinical settings.
In the last decade, computed tomographic pulmonary angiography (CTPA) has been introduced as a diagnostic test for a suspected PE. Its use has been steadily increasing over time . The number of detectors used during CTPA has also rapidly evolved from a single detector to multiple detectors. Multiple-detector CTPA allows better visualization of segmental and subsegmental pulmonary arteries [3,4], hence the proportion of patients with a suspected PE in whom isolated subsegmental PE (SSPE) is reported is rising with the increased use of multiple-detector CTPA [2,5]. A recent systematic review reported that the rate of SSPE diagnosis with multiple-detector CTPA was 9.4% (95% confidence interval [CI]: 5.5–14.3) . A recently published cohort study assessing 64 detector CTPA in patients with a suspected PE, and either likely pre-test probability (PTP) of PE (Wells Model) or unlikely PTP in combination with a positive D-dimer, has also reported that 12.4% of the confirmed PE were isolated to the sub-segmental pulmonary arteries .
The clinical significance of SSPE is unknown. A PE that is diagnosed by CTPA has been shown to be associated with a lower severity of illness and lower mortality [2,5]. A recent randomized controlled trial comparing the utility of CTPA with ventilation/perfusion (V/Q) scanning for the diagnosis of patients with a suspected PE showed that CTPA resulted in a significantly greater number of venous thromboembolism (VTE) diagnoses than did VQ scans; hence, more patients diagnosed by CTPA were treated with anticoagulants . In spite of this, the rate of VTE during the 3-month follow-up period was similar in untreated patients (i.e. in whom PE was excluded) who were randomized to the V/Q scan group . This suggests that the additional cases of PE detected by CTPA were clinically unimportant (i.e. represent actual PE that does not require anticoagulants, imaging artifacts or non-thrombotic intra-luminal filling defects). Given the increased incidence of SSPE and the controversy regarding the risks and benefits of anticoagulation in this patient population, we sought to ascertain the current diagnostic and therapeutic management of SSPE among Canadian thrombosis physicians.
In January 2011, members of the Thrombosis Interest Group of Canada (TIGC) were surveyed using a cross-sectional survey design. Physician members were identified through the membership list. The TIGC is a group of health care professionals whose primary interest is investigation and management of arterial and venous thrombosis as well as related issues. The group consists of 60 active members including 53 physicians. The survey was conducted on-line using Survey Monkey® and an invitation to complete the survey was sent out via email (http://www.surveymonkey.com/s/8TBD6ZW). A total of two reminders were also sent out at 1-week intervals. The survey consisted of two parts: (i) management of SSPE and segmental PE (using short descriptions of hypothetical patients and using five-point Likert scales); and (ii) assessment of the ‘absolute’ threshold of recurrent VTE risk after 3 months of follow-up below which one would not anticoagulate a patient with ‘PE’. The management of isolated SSPE was assessed using a case report of a patient presenting with symptomatic unprovoked single SSPE and no contraindication to anticoagulant therapy or relevant past medical history. Physicians were asked to describe their clinical management from a list of five possible choices ranging from no anticoagulant therapy or further diagnostic imaging to initiation of anticoagulation for at least 3 to 6 months (See Table 1). Then, changing one variable at a time (VTE risk factor, number or location of PE), physicians were asked to re-evaluate their clinical management. Management choices using the five-point Likert scale were identical for all cases. The order of the different management choices available was randomly assigned. Finally, respondents were asked to choose an ‘absolute’ threshold of recurrent VTE risk after 3 months of follow-up below which they would not anticoagulate a patient with PE. The ‘absolute’ threshold was meant to correspond to the upper bond of the 95% CI of the recurrent VTE risk below which physicians would feel comfortable not to start anticoagulant therapy. ‘Absolute’ risks ranged from 0% to 10% (0%, 0.5%, 1%, 2%, 3%, 5% and 10%).
|Management options||Single isolated SSPE|
No other risk factor (%)
|Single isolated SSPE + metastatic cancer (%)||Two SSPE|
No other risk factor (%)
|Single segmental PE (%)||Single lobar PE (%)|
|No anticoagulation + No further diagnostic imaging||7.1||4.8||2.4||2.4||0.0|
|No anticoagulation + VQ scan as next diagnostic test||28.6||16.7||28.6||9.5||4.8|
|No anticoagulation + Serial compressive U/S of lower extremities||40.5||31.0||11.9||0.0||0.0|
|Anticoagulation for at least 3–6 months||11.9||42.9||54.8||83.3||92.9|
The survey was pre-tested by hematologists and general internists to ensure face validity and accuracy (M.K., S.K., P.W., D.A., G.L. and M.R.). Data were collected online and entered into an EXCEL database. Not all respondents answered all questions and, therefore, proportions were calculated on the basis of the total number of respondents for any particular question.
A total of 42 (79% response rate) physicians completed the survey. Among respondents, 63% were male, 55% manage more than 20 patients with thrombosis per month and 39% manage 5 to 10 patients with SSPE per year.
The responses to the five clinical scenarios are depicted in Table 1. A total of 33% of respondents said they are comfortable with a threshold of 2% rate of recurrent VTE at 3 months below which they would not initiate anticoagulation for PE (range: 0.5–5%). Finally, approximately 97% of respondents either strongly agree or agree that clinical studies assessing the management of SSPE are needed.
In this cross-sectional survey of practicing Canadian thrombosis physicians, we found that, in spite of sparse data in the literature and consensus guidelines, a large proportion of patients with either single- or multiple-isolated SSPE is managed without the use of anticoagulation using alternative diagnostic imaging modalities (i.e. US or V/Q scans) or by withholding anticoagulation and following patients closely. Physicians seem to be comfortable withholding anticoagulation therapy if the perceived risk of recurrent VTE at 3 months is < 2%. Clinical management studies assessing the management of SSPE without anticoagulation using the above threshold are urgently needed to ensure the safety of this management strategy.
Isolated SSPE might be safely managed without the initiation of anticoagulation. Sub-segmental PE was shown to be most prevalent among patients with low-probability VQ scans in the PIOPED study . Several prospective cohort studies have demonstrated that some patients with low or intermediate V/Q scan results can be safely managed without anticoagulation using a non-invasive diagnostic strategy combining clinical assessment, D-dimer testing and US of the lower extremities [10,11]. Many of the latter patients would presumably have been diagnosed with isolated SSPE if CTPA were conducted and presumably these isolated SSPE do not require anticoagulation.
The increased incidence of SSPE diagnosed by CTPA could have important consequences for patient care. Potential radiation exposure with CTPA, especially if repeated, needs to be considered in patients with suspected PE and clinical monitoring of such outcomes should be part of future clinical trials.
The risk/benefit ratio of anticoagulant therapy is also important to assess, as an increase in the diagnosis of PE will result in more patients being exposed to anticoagulants and their associated risks. To date, a total of 52 patients with SSPE diagnosed by CTPA who did not receive anticoagulation treatment have been reported in the literature [12,13]. None of these patients had a recurrent fatal PE. A retrospective cohort study reported that approximately 5.3% of patients with isolated SSPE receiving anticoagulant therapy will experience a bleeding episode . The case-fatality rate of major bleeding in patients taking oral anticoagulant therapy for VTE is 11.3% (95% CI: 7.5–15.9) . Furthermore, resource allocation for anticoagulant therapy (including drug costs, monitoring and follow-up care) and potential costs associated with major bleeding complications need to be considered. Anticoagulant therapy also imposes inconvenience for the patient, with potential dietary restrictions, possible activity restrictions and frequent follow-up appointments.
In summary, the present results indicate that the management of SSPE is controversial among thrombosis experts. Clinical equipoise exists regarding the management of single and multiple isolated SSPE. Diagnostic and therapeutic management studies of patients with single and multiple isolated SSPE are needed to address whether anticoagulant treatment is of net clinical benefit. Studies identifying patients with SSPE at high risk of recurrent VTE are also required to assess if anticoagulation is warranted in some subgroups of patients.