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Three Part Question

1. In [patients with isolated subsegmental pulmonary emboli]

2. is [oral anticoagulation therapy] necessary

3. [to reduce mortality and morbidity]?

Clinical Scenario

A 36 year-old gentleman presented with pleuritic chest pain to the emergency department of St Vincent’s Hospital, Melbourne. He was low-risk for pulmonary embolism with a modified Well’s score of 0 but had a raised d-dimer of 0.7 mcg/ml. A CT pulmonary artery scan (CTPA) was performed, showing a subsegmental pulmonary embolus . He was subsequently admitted to hospital for anticoagulation and investigation of underlying risk factors.

The prospect of systemic anticoagulation for three months was unappealing for him. He was otherwise clinically well and was a young person with an active lifestyle. This raised the question of whether the use of oral anticoagulation was justified in this gentleman, or whether the potential harm would outweigh the benefits.

Search Strategy

The following search strategy was used:
Medline (54 papers identified): MM Pulmonary Embolism OR TI Pulmonary embol* AND subsegment OR sub segment* AND anticoag* OR MH anticoagulants OR TI therap* OR TI manag* OR TI treat*.
Embase (51 papers identified, nil additional): Pulmonary and embol* AND subsegment OR sub segment* AND anticoag OR anticoagulants OR therap* OR manag* OR treatment.
Cinahl (No additional papers identified): MM Pulmonary Embolism OR TI Pulmonary embol* AND subsegment OR sub segment* AND anticoag* OR MH anticoagulants OR TI therap* OR TI manag* OR TI treat*.
Cochrane database (No additional papers identified): Pulmonary embolus OR embolism AND subsegmental OR peripheral.
Reference lists of major papers identified from this search were scanned for any studies not identified by the database search.

Exclusion criteria:
- Studies assessing patients with clots in larger vessels than the subsegmental arteries.
- Follow-up of less than three months after diagnosis.
- Studies performed prior to the MDCT-era (before 2002).
Exclusion criteria:
- Studies assessing patients with clots in larger vessels than the subsegmental arteries.
- Follow-up of less than three months after diagnosis.
- Studies performed prior to the MDCT-era (before 2002).

Search Outcome

Three studies were identified from the literature search that met the criteria.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Eyer et al 2005 USA	Patients diagnosed with subsegmental pulmonary embolism on CTPA.	A retrospective single-centre study assessed the clinician’s response to 77 MDCTs that were reported positive for ISSPE. The researchers reviewed 1,435 scans and 77 (5%) were reported as showing a subsegmental pulmonary embolism. 130 scans were reported as inconclusive and these patients were also followed-up. 32 patients with ISSPE received no anticoagulation (34%). The decision on whether to anticoagulate was based on individual clinician judgement. No clinical probability scores or protocol were used. It was unclear how many untreated patients were actually misdiagnosed and in what proportion an active decision not to anticoagulant was made. 25 of the 32 patients were followed-up at 3-months. This was done by retrospective analysis of the hospital records. Two of the untreated patients returned with symptoms of recurrent pulmonary embolism but repeat CTPA was negative. None of the patients, treated or untreated with anticoagulants, had recurrence of venous thromboembolism at 3 months.	32 patients with ISSPE (34%) received no anticoagulation. 25 were followed up at three months. None had recurrence of venous thromboembolism.		This study was limited by being performed in a single center. It was a retrospective review of case notes and so may have missed patients who presented to another hospital with pulmonary embolism or who died and were not accounted for. It was limited by small numbers and was designed to assess the response of clinicians to the radiographic diagnosis of ISSPE rather than the safety of withholding anticoagulation. A high proportion of scans were reported as inconclusive (9%). The experience of the radiologist reporting the scan was unclear from the methodology and the scans were not independently reviewed. It is possible that there were a number of false positive and false negative reports in the ISSPE and inconclusive groups. Only 78% of untreated patients had records of having been followed-up at three months and this may have resulted in selection bias.
Donato 2010 USA	Patients diagnosed with subsegmental PE on CTPA.	This was a retrospective single-centre study that reviewed the clinical outcomes of 93 patients who had a positive radiology report for subsegmental PE on CTPA. Fifteen patients who had a co-existing deep vein thrombosis (DVT) were excluded. 10,453 CTPA radiology reports over a 74- month period were analysed, with 1,463 being positive for PE. Patients were followed up over a three-month period to assess outcome and bleeding risk. Twenty-two patients (23.6% of those with ISSPEs) were treated conservatively. 20 out of 22 of the untreated patients had a negative doppler ultrasound scan, excluding DVT. Follow-up was performed by review of clinical records and direct contact with the outpatient physician. The untreated group had no recurrent PE at the end of three months. All patients were accounted for and patients who could not be found had death records requested. All CT scans were reported by a board certified radiologist and the positive scans were then re-reviewed externally to confirm the diagnosis. The decision to anticoagulate depended on individual physicians and there was no protocol to guide this decision. It was unclear whether there was any clinically significant difference between the treatment and non-treatment groups. Eight adverse events due to haemorrhage were reported in the treatment group. Two deaths were reported but thought to be unrelated to thromboembolic disease. Recurrence of subsegmental emboli was reported in one patient who was actively treated. This was at 15 days and following IVC filter placement and warfarin commencement. This was the largest study on clinical outcomes in ISSPE. It involved the interpretation of data over six years and on over 10,000 CT scans. Very few patients were lost to follow-up.	22 out of 93 patients with ISSPE treated conservatively (23.6%). Nil had recurrence of venous thromboembolism at three months.		Single-centre retrospective study. No protocol determining treatment. Limited by small numbers of untreated patients. The majority of patients with ISSPE were treated with anticoagulation.

Comment(s)

Current evidence base consists of retrospective studies including small numbers of patients. There is insufficient evidence to recommend a change from current practice.

Clinical Bottom Line

Maintaining a practice of routine anticoagulation, unless there are contraindications or specific reasons not to, seems a prudent and reasonable strategy with the current evidence base.

References

1. Eyer et al Clinicians’ Response to Radiologists’ Reports of Isolated Subsegmental Pulmonary Embolism or Inconclusive Interpretation of Pulmonary Embolism Using MDCT American Journal of Radiology February 2005; 623-628
2. Donato et al Clinical Outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography Thrombosis Research October 2010 126: 266-270
3. Cha et al Clinical characteristics of patients with peripheral pulmonary embolism. Respiration 2010; 80 (6) 500-508