Reminder of important clinical lesson
CASE REPORT
Recurrent pulmonary embolus despite adequate anticoagulation: the case for routine cancer screening, prompted by an uncommon cause Daniel Bendel,1 Chee Yee Loong2 1
Department of Anaesthetics and Critical Care, Northampton General Hospital, Northampton, UK 2 Department of Cardiovascular Medicine, The Whittington Hospital, London, UK Correspondence to Dr Chee Yee Loong, [email protected] Accepted 8 September 2014
To cite: Bendel D, Loong CY. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2013202295
SUMMARY A middle-aged patient presented with dyspnoea, haemoptysis and weight loss following a recent admission for pulmonary embolus, diagnosed on CT pulmonary angiogram (CTPA). The patient was anticoagulated with warfarin to a therapeutic range 2–3. There was no relevant medical history. On examination, the pulse was 105 bpm and blood pressure was 70/50 mm Hg. Oxygen saturation was 94% on air. Repeat CTPA revealed extension of the clot burden, now a saddle embolus occluding pulmonary outflow. The patient underwent emergency surgical embolectomy, and histology of the excised clot revealed the underlying cause—a malignant, high-grade sarcoma of the pulmonary vasculature. The target international normalised ratio was increased to 3–4. Postoperatively, the patient developed a large malignant pericardial effusion which required urgent percutaneous drainage. The patient eventually underwent targeted chemotherapy, which extended patient survival. The patient passed away a year later from progressive right-sided heart failure as a result of cor pulmonale.
compromised, but deemed stable enough for transfer to the cardiothoracic unit. The serendipitous emergence of an underlying malignancy of the pulmonary vasculature on histology raises questions about the relationship between the clues in the history and the role of cancer screening in recurrent, unheralded venous thromboembolism (VTE). It also raises questions concerning the preferential role of surgery and histology in this context. This case also highlights a rare cause of PE that was only revealed due to the availability of resected clot; a high-grade pleiomorphic sarcoma of the intima of the pulmonary vasculature (grade III). As well as highlighting a rare cause of PE, we discuss the key role surgical embolectomy can play in making a diagnosis. We also discuss the need for extensive cancer screening in cases where VTE is recurrent and unheralded, and consider whether the extent of coverage on the issue in the BTS and National Institute for Health and Care Excellence (NICE) guidelines is adequate.
BACKGROUND
CASE PRESENTATION
The present case reports how surgical embolectomy was utilised in preference to thrombolysis in treating a massive pulmonary embolus (PE). It proved to be both therapeutic and diagnostic, revealing an unexpected underlying cause. Surgical embolectomy and subsequent histology of the resected clot provided the definitive diagnosis and enabled lifeprolonging chemotherapy. This case also raises questions about screening for malignancy in unheralded PE, recurrent or otherwise. The initial presentation was that of hypoxia alone, and PE was treated with warfarin at a target international normalised ratio (INR) of 2.5. However, the patient presented for a second time with breathlessness and haemodynamic compromise, with evidence of extension of the pulmonary emboli on CT, despite adequate anticoagulation. This was now in the context of weight loss and fatigue. The patient’s case was discussed at an MDT comprising of cardiological, respiratory, cardiothoracic and intensive care health professionals. On account of the severity of the patient’s symptoms, the progression of the disease and the availability of a local cardiothoracic surgical centre, the decision was made to refer for surgical embolectomy. This was in preference to thrombolysis, which is usually first-line management for haemodynamically significant PE, as per the British Thoracic Society (BTS) guidelines. The patient was haemodynamically
A patient in their 60s presented to a hospital with a week-long history of worsening dyspnoea and a marked reduction in exercise tolerance to 30 yards. There was concomitant fresh frank haemoptysis, fatigue, anorexia and unintentional weight loss of 9 kg over the course of a month. This was in the context of a previous admission a month beforehand, where dyspnoea and hypoxia was shown to be due to a PE on CT pulmonary angiogram (CTPA). There was a clot extending from the main pulmonary artery, extending into the right pulmonary artery and branches (figure 1). The patient was treated with warfarin, with a target INR set
Figure 1 CT pulmonary angiogram during first presentation.
Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
1
Reminder of important clinical lesson between 2 and 3. This was within the target range on readmission. Other history included chronic lymphocytic leukaemia (CLL) stage 0, mumps and tonsillectomy. The patient’s mother was diagnosed with breast cancer in her 60 s. On examination, there were reduced breath sounds in the right upper zone of the lung. The jugular venous pulse was elevated at 6 cm from the sternal angle. The patient had a tachycardia of 105 bpm, a blood pressure of 70/50 mm Hg, a respiratory rate of 30 breaths per minute and saturations of 94% on room air. Saturations increased to 97% on 2 L/min of O2. There were no signs of lymphadenopathy, or of deep vein thrombosis. Arterial blood gas on 2 L of O2 demonstrated pH 7.46, pCO2 4.2 kPa, pO2 12.5 kPa and HCO3 22.3 mmol/L. Blood tests revealed a white cell count of 18.2×109/L (lymphocytes 7.5×109/L, neutrophils 9.1×109/L) and a C reactive protein of 21 mg/L. The INR remained within the therapeutic range. The patient received emergency intravenous fluid resuscitation, though this had only a modest effect on blood pressure. The patient was then transferred to the intensive care unit for close monitoring. An urgent repeat CTPA revealed a saddle embolus, with propagation of the clot from the pulmonary valve extending into both main pulmonary arteries (figure 2). There was occlusion of pulmonary artery outflow as well as signs of right ventricular failure, with reflux of contrast into the inferior vena cava and the hepatic veins. There were numerous cavitating lesions within the right upper lobe. These were reported as pulmonary infarcts, consistent with a large and unresolved PE. These changes were new in comparison to the CTPA performed during the previous admission and were felt to be in keeping with the clinical progression of the patient’s clot burden. On account of the marked increase in clot burden, the patient was restarted on intravenous heparin until the INR reached a new target range 3–4. The case was discussed at a multidisciplinary meeting, comprising of radiologists, cardiologists, respiratory physicians, cardiothoracic surgeons and intensive care physicians. The combination of continuing clot propagation despite adequate anticoagulation, haemodynamic compromise and the availability of cardiothoracic surgery locally shifted the balance in favour of emergency pulmonary embolectomy. Despite hypotension, the blood pressure remained stable and neither inotropes nor fluid challenges were deemed necessary. As such, the patient was considered stable enough for an interhospital transfer. At embolectomy, a 6 cm clot was resected and sent for histology (figure 3).
Figure 3 The excised clot (a cast of the pulmonary trunk and left and right pulmonary arteries).
INVESTIGATIONS CTPA on first presentation revealed a large clot within the root of the pulmonary artery close to the pulmonary valve, with a large thrombus extending down to the lobar branches of all three right-sided lobes. There were no other features (figure 1). CTPA on readmission demonstrated extension of original clot, now occluding both the right and left main pulmonary arteries and the main pulmonary artery; a saddle embolus. Large cavitating filling defects were evident and were reported as pulmonary infarcts. There was evidence of right heart strain. There was no mediastinal lymphadenopathy (figure 2). Histology of the resected clot showed evidence of a highgrade pleiomorphic sarcoma of the intima of the pulmonary vasculature (grade III; figure 3).
DIFFERENTIAL DIAGNOSIS ▸ A repeat episode of pulmonary embolism ▸ Hypovolaemic shock from haemoptysis due to PE/pulmonary infarction ▸ Sepsis from pulmonary infarction
TREATMENT The target INR was increased from 2–3 to 3–4, bridged with intravenous heparin. The patient was transferred to a nearby cardiothoracic centre for urgent surgical embolectomy.
OUTCOME AND FOLLOW-UP
Figure 2 CT pulmonary angiogram on readmission showing marked extension of clot. 2
Following surgical embolectomy, the patient developed marked peripheral oedema. Intravenous furosemide initially had a limited effect. Echocardiography demonstrated a new large global pericardial effusion, measuring up to 4.3 cm at the right ventricular base, with signs of early right ventricular diastolic Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
Reminder of important clinical lesson
Figure 4 Postoperative global pericardial effusion with signs of diastolic right ventricular collapse.
collapse (figure 4). The patient underwent urgent percutaneous pericardiocentesis, which provided good symptomatic relief and allowed for a successful diuresis. Although improved, the patient remained hypoxic throughout the postoperative period and was initiated on long-term oxygen therapy. The patient was referred to oncology in view of the histology findings, and eventually started on chemotherapy when fit. The patient completed four cycles of doxyrubicin. Two months later, the patient presented with a collapse and CTPA demonstrated an increased clot burden despite adequate anticoagulation. There were also new lung metastases with multiple enlarged mediastinal and iliac lymph nodes. The patient suffered from progressively worsening dyspnoea, pulmonary hypertension and right ventricular failure. This resulted in worsening peripheral oedema which was refractory to diuretics. The patient was started on an oral morphine solution for palliation of dyspnoea and a reducing regimen of dexamethasone. His clinical condition continued to deteriorate and the patient passed away due to cor pulmonale, secondary to pulmonary sarcoma. Despite the expected outcome, the additional time bought by chemotherapy allowed the patient to organise a number of personal matters, including writing a will and making other preparations for his death.
DISCUSSION The 2003 BTS guidance on the treatment of PE does not elaborate on the investigation and management of massive PE. It cites thrombolysis as first-line treatment and says that invasive approaches such as thrombus fragmentation and IVC filter insertion should be considered where the ‘facilities and expertise are readily available’. A distinction between the use and suitability of the two treatment modalities in different clinical scenarios is not made. With regard to investigating for an occult cancer in idiopathic VTE, further investigations are warranted “when it is suspected clinically, on chest radiography, or on routine blood tests.”1 These guidelines have since been superceded by the 2012 NICE guidance on venous thromboembolic diseases. The fullguidance document notes the role of surgical embolectomy in haemodynamically unstable patients, particularly in patient subgroups where pharmacological thrombolytic therapy is Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
contra-indicated or has failed. However, when assessing the efficacy and safety of a number of thrombolytic therapies (both pharmacological and mechanical), surgical embolectomy was excluded from the analysis on account of the fact that only a small number of clinical trials have been performed. As such, surgical embolectomy is neither promoted nor discouraged by current NICE guidance.2 However, a recent study in the European Journal of Cardiothoracic Surgery found that early mortality rates between thrombolysis and surgical embolectomy were comparable. It also found that the risk of bleeding with surgical embolectomy was far less than that of thrombolysis, which stands at 22%.3 Up until recently, there has been a paucity of guidance in the area of unheralded VTE and the routine screening of patients for malignancy. This is despite half of all cases of VTE having an underlying cause. A recent multicentre randomised controlled trial (The SOMIT trial) randomised 200 patients with idiopathic VTE to ‘no further diagnostic studies’ and ‘extensive cancer diagnostic screen’ (including CT imaging). Thirteen of the 99 patients randomised to ‘extensive cancer diagnostic screen’ were found to have cancer during their admission with a high degree of sensitivity. Cancers were detected primarily in those over the age of 60 and at a much earlier and less advanced stage. The study therefore concluded that patients over the age of 60 presenting with unheralded VTE should be extensively screened for cancer.4 This is partially reflected in the recent 2013 NICE quality standards publication, which asserts that these patients should be managed on the 2-week pathway. However, the diagnostic screen recommended by NICE is limited to physical examination, blood tests, a chest X-ray and urinalysis. Imaging
Learning points ▸ Unheralded or recurrent venous thromboembolism should raise the possibility of a malignancy as the underlying cause. There is now both evidence and guidance to suggest that it should be investigated extensively, and in a timely manner. ▸ The first-line management of haemodynamically significant pulmonary embolus (PE) is usually thrombolysis. However, there are certain clinical circumstances when surgical embolectomy is a more appropriate course of management. Unheralded or recurrent PE that is refractory to anticoagulation is one of these circumstances, as it provides both histology as well as relief from the clot burden. Other less invasive approaches such as transcatheter sampling provide an alternative route to yield sample histology and should also be considered. ▸ Other differential diagnoses for haemodynamic compromise in this context include extension of clot, sepsis from pulmonary infarction and frank haemoptysis. However, the failure to respond to adequate anticoagulation and the presence of progressive cavitating lung nodules are additional clues that point towards a malignancy. ▸ Although rare, primary pleiomorphic sarcoma of the pulmonary vasculature is one such cause and should be excluded. A high index of suspicion is required in these cases, as the sarcoma can be masked by a secondary PE. Ongoing clot extension despite apparently adequate anticoagulation should prompt the clinician to consider this rare but important diagnosis. 3
Reminder of important clinical lesson modalities such as CT scan are not mentioned.5 The NICE quality standards fall short in recommending exactly how far to screen patients for malignancy. This is in contrast to the SOMIT trial, where CT scanning was actively offered. The evidence base exists to suggest that patients with unheralded VTE in general require extensive cancer screening. This coupled with the utility and safety of surgical embolectomy opens up new pathways of investigation and management for the physician managing patients with recurrent, unheralded PE. We would suggest that massive PE in patients over the age of 60, reporting of anorexia and unintentional weight loss and/or the recurrence of VTE, especially in the presence of adequate anticoagulation, should prompt the suspicion of a malignancy and initiate an extensive cancer screen, including CT scanning. We would also suggest offering surgical embolectomy with clot histology as the treatment of choice in preference to thrombolysis, should the expertise be locally available, and the patient be stable enough for transfer. In this manner, is it not only possible to quickly remove large clots but also provide an opportunity for histological or radiological diagnosis. This is not explicitly mentioned in current BTS or NICE guidelines.
Acknowledgements The authors thank Dr Batia Friedmann. Contributors DB was conceiver and primary author of the article. CYL acted as senior author, making revisions where necessary and approving the final draft. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
2 3
4
5
British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58: 470–83. National Institute for Health and Care Excellence. Venous thromboembolic diseases. CG144. London: National Institute for Health and Care Excellence, 2012. Aymard T, Kadner A, Widmer A, et al. Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy—should surgical indications be revisited? Eur J Cardiothorac Surg 2013;43:90–4. Piccioli A, Lensing AWA, Prins MH, et al; SOMIT Investigators Group. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost 2004;2: 884–9. National Institute for Health and Care Excellence. Quality standard for diagnosis and management of venous thromboembolic diseases. QS29. London: National Institute for Health and Care Excellence, 2013.
Copyright 2014 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
CASE REPORT
Recurrent pulmonary embolus despite adequate anticoagulation: the case for routine cancer screening, prompted by an uncommon cause Daniel Bendel,1 Chee Yee Loong2 1
Department of Anaesthetics and Critical Care, Northampton General Hospital, Northampton, UK 2 Department of Cardiovascular Medicine, The Whittington Hospital, London, UK Correspondence to Dr Chee Yee Loong, [email protected] Accepted 8 September 2014
To cite: Bendel D, Loong CY. BMJ Case Rep Published online: [please include Day Month Year] doi:10.1136/bcr-2013202295
SUMMARY A middle-aged patient presented with dyspnoea, haemoptysis and weight loss following a recent admission for pulmonary embolus, diagnosed on CT pulmonary angiogram (CTPA). The patient was anticoagulated with warfarin to a therapeutic range 2–3. There was no relevant medical history. On examination, the pulse was 105 bpm and blood pressure was 70/50 mm Hg. Oxygen saturation was 94% on air. Repeat CTPA revealed extension of the clot burden, now a saddle embolus occluding pulmonary outflow. The patient underwent emergency surgical embolectomy, and histology of the excised clot revealed the underlying cause—a malignant, high-grade sarcoma of the pulmonary vasculature. The target international normalised ratio was increased to 3–4. Postoperatively, the patient developed a large malignant pericardial effusion which required urgent percutaneous drainage. The patient eventually underwent targeted chemotherapy, which extended patient survival. The patient passed away a year later from progressive right-sided heart failure as a result of cor pulmonale.
compromised, but deemed stable enough for transfer to the cardiothoracic unit. The serendipitous emergence of an underlying malignancy of the pulmonary vasculature on histology raises questions about the relationship between the clues in the history and the role of cancer screening in recurrent, unheralded venous thromboembolism (VTE). It also raises questions concerning the preferential role of surgery and histology in this context. This case also highlights a rare cause of PE that was only revealed due to the availability of resected clot; a high-grade pleiomorphic sarcoma of the intima of the pulmonary vasculature (grade III). As well as highlighting a rare cause of PE, we discuss the key role surgical embolectomy can play in making a diagnosis. We also discuss the need for extensive cancer screening in cases where VTE is recurrent and unheralded, and consider whether the extent of coverage on the issue in the BTS and National Institute for Health and Care Excellence (NICE) guidelines is adequate.
BACKGROUND
CASE PRESENTATION
The present case reports how surgical embolectomy was utilised in preference to thrombolysis in treating a massive pulmonary embolus (PE). It proved to be both therapeutic and diagnostic, revealing an unexpected underlying cause. Surgical embolectomy and subsequent histology of the resected clot provided the definitive diagnosis and enabled lifeprolonging chemotherapy. This case also raises questions about screening for malignancy in unheralded PE, recurrent or otherwise. The initial presentation was that of hypoxia alone, and PE was treated with warfarin at a target international normalised ratio (INR) of 2.5. However, the patient presented for a second time with breathlessness and haemodynamic compromise, with evidence of extension of the pulmonary emboli on CT, despite adequate anticoagulation. This was now in the context of weight loss and fatigue. The patient’s case was discussed at an MDT comprising of cardiological, respiratory, cardiothoracic and intensive care health professionals. On account of the severity of the patient’s symptoms, the progression of the disease and the availability of a local cardiothoracic surgical centre, the decision was made to refer for surgical embolectomy. This was in preference to thrombolysis, which is usually first-line management for haemodynamically significant PE, as per the British Thoracic Society (BTS) guidelines. The patient was haemodynamically
A patient in their 60s presented to a hospital with a week-long history of worsening dyspnoea and a marked reduction in exercise tolerance to 30 yards. There was concomitant fresh frank haemoptysis, fatigue, anorexia and unintentional weight loss of 9 kg over the course of a month. This was in the context of a previous admission a month beforehand, where dyspnoea and hypoxia was shown to be due to a PE on CT pulmonary angiogram (CTPA). There was a clot extending from the main pulmonary artery, extending into the right pulmonary artery and branches (figure 1). The patient was treated with warfarin, with a target INR set
Figure 1 CT pulmonary angiogram during first presentation.
Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
1
Reminder of important clinical lesson between 2 and 3. This was within the target range on readmission. Other history included chronic lymphocytic leukaemia (CLL) stage 0, mumps and tonsillectomy. The patient’s mother was diagnosed with breast cancer in her 60 s. On examination, there were reduced breath sounds in the right upper zone of the lung. The jugular venous pulse was elevated at 6 cm from the sternal angle. The patient had a tachycardia of 105 bpm, a blood pressure of 70/50 mm Hg, a respiratory rate of 30 breaths per minute and saturations of 94% on room air. Saturations increased to 97% on 2 L/min of O2. There were no signs of lymphadenopathy, or of deep vein thrombosis. Arterial blood gas on 2 L of O2 demonstrated pH 7.46, pCO2 4.2 kPa, pO2 12.5 kPa and HCO3 22.3 mmol/L. Blood tests revealed a white cell count of 18.2×109/L (lymphocytes 7.5×109/L, neutrophils 9.1×109/L) and a C reactive protein of 21 mg/L. The INR remained within the therapeutic range. The patient received emergency intravenous fluid resuscitation, though this had only a modest effect on blood pressure. The patient was then transferred to the intensive care unit for close monitoring. An urgent repeat CTPA revealed a saddle embolus, with propagation of the clot from the pulmonary valve extending into both main pulmonary arteries (figure 2). There was occlusion of pulmonary artery outflow as well as signs of right ventricular failure, with reflux of contrast into the inferior vena cava and the hepatic veins. There were numerous cavitating lesions within the right upper lobe. These were reported as pulmonary infarcts, consistent with a large and unresolved PE. These changes were new in comparison to the CTPA performed during the previous admission and were felt to be in keeping with the clinical progression of the patient’s clot burden. On account of the marked increase in clot burden, the patient was restarted on intravenous heparin until the INR reached a new target range 3–4. The case was discussed at a multidisciplinary meeting, comprising of radiologists, cardiologists, respiratory physicians, cardiothoracic surgeons and intensive care physicians. The combination of continuing clot propagation despite adequate anticoagulation, haemodynamic compromise and the availability of cardiothoracic surgery locally shifted the balance in favour of emergency pulmonary embolectomy. Despite hypotension, the blood pressure remained stable and neither inotropes nor fluid challenges were deemed necessary. As such, the patient was considered stable enough for an interhospital transfer. At embolectomy, a 6 cm clot was resected and sent for histology (figure 3).
Figure 3 The excised clot (a cast of the pulmonary trunk and left and right pulmonary arteries).
INVESTIGATIONS CTPA on first presentation revealed a large clot within the root of the pulmonary artery close to the pulmonary valve, with a large thrombus extending down to the lobar branches of all three right-sided lobes. There were no other features (figure 1). CTPA on readmission demonstrated extension of original clot, now occluding both the right and left main pulmonary arteries and the main pulmonary artery; a saddle embolus. Large cavitating filling defects were evident and were reported as pulmonary infarcts. There was evidence of right heart strain. There was no mediastinal lymphadenopathy (figure 2). Histology of the resected clot showed evidence of a highgrade pleiomorphic sarcoma of the intima of the pulmonary vasculature (grade III; figure 3).
DIFFERENTIAL DIAGNOSIS ▸ A repeat episode of pulmonary embolism ▸ Hypovolaemic shock from haemoptysis due to PE/pulmonary infarction ▸ Sepsis from pulmonary infarction
TREATMENT The target INR was increased from 2–3 to 3–4, bridged with intravenous heparin. The patient was transferred to a nearby cardiothoracic centre for urgent surgical embolectomy.
OUTCOME AND FOLLOW-UP
Figure 2 CT pulmonary angiogram on readmission showing marked extension of clot. 2
Following surgical embolectomy, the patient developed marked peripheral oedema. Intravenous furosemide initially had a limited effect. Echocardiography demonstrated a new large global pericardial effusion, measuring up to 4.3 cm at the right ventricular base, with signs of early right ventricular diastolic Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
Reminder of important clinical lesson
Figure 4 Postoperative global pericardial effusion with signs of diastolic right ventricular collapse.
collapse (figure 4). The patient underwent urgent percutaneous pericardiocentesis, which provided good symptomatic relief and allowed for a successful diuresis. Although improved, the patient remained hypoxic throughout the postoperative period and was initiated on long-term oxygen therapy. The patient was referred to oncology in view of the histology findings, and eventually started on chemotherapy when fit. The patient completed four cycles of doxyrubicin. Two months later, the patient presented with a collapse and CTPA demonstrated an increased clot burden despite adequate anticoagulation. There were also new lung metastases with multiple enlarged mediastinal and iliac lymph nodes. The patient suffered from progressively worsening dyspnoea, pulmonary hypertension and right ventricular failure. This resulted in worsening peripheral oedema which was refractory to diuretics. The patient was started on an oral morphine solution for palliation of dyspnoea and a reducing regimen of dexamethasone. His clinical condition continued to deteriorate and the patient passed away due to cor pulmonale, secondary to pulmonary sarcoma. Despite the expected outcome, the additional time bought by chemotherapy allowed the patient to organise a number of personal matters, including writing a will and making other preparations for his death.
DISCUSSION The 2003 BTS guidance on the treatment of PE does not elaborate on the investigation and management of massive PE. It cites thrombolysis as first-line treatment and says that invasive approaches such as thrombus fragmentation and IVC filter insertion should be considered where the ‘facilities and expertise are readily available’. A distinction between the use and suitability of the two treatment modalities in different clinical scenarios is not made. With regard to investigating for an occult cancer in idiopathic VTE, further investigations are warranted “when it is suspected clinically, on chest radiography, or on routine blood tests.”1 These guidelines have since been superceded by the 2012 NICE guidance on venous thromboembolic diseases. The fullguidance document notes the role of surgical embolectomy in haemodynamically unstable patients, particularly in patient subgroups where pharmacological thrombolytic therapy is Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
contra-indicated or has failed. However, when assessing the efficacy and safety of a number of thrombolytic therapies (both pharmacological and mechanical), surgical embolectomy was excluded from the analysis on account of the fact that only a small number of clinical trials have been performed. As such, surgical embolectomy is neither promoted nor discouraged by current NICE guidance.2 However, a recent study in the European Journal of Cardiothoracic Surgery found that early mortality rates between thrombolysis and surgical embolectomy were comparable. It also found that the risk of bleeding with surgical embolectomy was far less than that of thrombolysis, which stands at 22%.3 Up until recently, there has been a paucity of guidance in the area of unheralded VTE and the routine screening of patients for malignancy. This is despite half of all cases of VTE having an underlying cause. A recent multicentre randomised controlled trial (The SOMIT trial) randomised 200 patients with idiopathic VTE to ‘no further diagnostic studies’ and ‘extensive cancer diagnostic screen’ (including CT imaging). Thirteen of the 99 patients randomised to ‘extensive cancer diagnostic screen’ were found to have cancer during their admission with a high degree of sensitivity. Cancers were detected primarily in those over the age of 60 and at a much earlier and less advanced stage. The study therefore concluded that patients over the age of 60 presenting with unheralded VTE should be extensively screened for cancer.4 This is partially reflected in the recent 2013 NICE quality standards publication, which asserts that these patients should be managed on the 2-week pathway. However, the diagnostic screen recommended by NICE is limited to physical examination, blood tests, a chest X-ray and urinalysis. Imaging
Learning points ▸ Unheralded or recurrent venous thromboembolism should raise the possibility of a malignancy as the underlying cause. There is now both evidence and guidance to suggest that it should be investigated extensively, and in a timely manner. ▸ The first-line management of haemodynamically significant pulmonary embolus (PE) is usually thrombolysis. However, there are certain clinical circumstances when surgical embolectomy is a more appropriate course of management. Unheralded or recurrent PE that is refractory to anticoagulation is one of these circumstances, as it provides both histology as well as relief from the clot burden. Other less invasive approaches such as transcatheter sampling provide an alternative route to yield sample histology and should also be considered. ▸ Other differential diagnoses for haemodynamic compromise in this context include extension of clot, sepsis from pulmonary infarction and frank haemoptysis. However, the failure to respond to adequate anticoagulation and the presence of progressive cavitating lung nodules are additional clues that point towards a malignancy. ▸ Although rare, primary pleiomorphic sarcoma of the pulmonary vasculature is one such cause and should be excluded. A high index of suspicion is required in these cases, as the sarcoma can be masked by a secondary PE. Ongoing clot extension despite apparently adequate anticoagulation should prompt the clinician to consider this rare but important diagnosis. 3
Reminder of important clinical lesson modalities such as CT scan are not mentioned.5 The NICE quality standards fall short in recommending exactly how far to screen patients for malignancy. This is in contrast to the SOMIT trial, where CT scanning was actively offered. The evidence base exists to suggest that patients with unheralded VTE in general require extensive cancer screening. This coupled with the utility and safety of surgical embolectomy opens up new pathways of investigation and management for the physician managing patients with recurrent, unheralded PE. We would suggest that massive PE in patients over the age of 60, reporting of anorexia and unintentional weight loss and/or the recurrence of VTE, especially in the presence of adequate anticoagulation, should prompt the suspicion of a malignancy and initiate an extensive cancer screen, including CT scanning. We would also suggest offering surgical embolectomy with clot histology as the treatment of choice in preference to thrombolysis, should the expertise be locally available, and the patient be stable enough for transfer. In this manner, is it not only possible to quickly remove large clots but also provide an opportunity for histological or radiological diagnosis. This is not explicitly mentioned in current BTS or NICE guidelines.
Acknowledgements The authors thank Dr Batia Friedmann. Contributors DB was conceiver and primary author of the article. CYL acted as senior author, making revisions where necessary and approving the final draft. Competing interests None. Provenance and peer review Not commissioned; externally peer reviewed.
REFERENCES 1
2 3
4
5
British Thoracic Society Standards of Care Committee Pulmonary Embolism Guideline Development Group. British Thoracic Society guidelines for the management of suspected acute pulmonary embolism. Thorax 2003;58: 470–83. National Institute for Health and Care Excellence. Venous thromboembolic diseases. CG144. London: National Institute for Health and Care Excellence, 2012. Aymard T, Kadner A, Widmer A, et al. Massive pulmonary embolism: surgical embolectomy versus thrombolytic therapy—should surgical indications be revisited? Eur J Cardiothorac Surg 2013;43:90–4. Piccioli A, Lensing AWA, Prins MH, et al; SOMIT Investigators Group. Extensive screening for occult malignant disease in idiopathic venous thromboembolism: a prospective randomized clinical trial. J Thromb Haemost 2004;2: 884–9. National Institute for Health and Care Excellence. Quality standard for diagnosis and management of venous thromboembolic diseases. QS29. London: National Institute for Health and Care Excellence, 2013.
Copyright 2014 BMJ Publishing Group. All rights reserved. For permission to reuse any of this content visit http://group.bmj.com/group/rights-licensing/permissions. BMJ Case Report Fellows may re-use this article for personal use and teaching without any further permission. Become a Fellow of BMJ Case Reports today and you can: ▸ Submit as many cases as you like ▸ Enjoy fast sympathetic peer review and rapid publication of accepted articles ▸ Access all the published articles ▸ Re-use any of the published material for personal use and teaching without further permission For information on Institutional Fellowships contact [email protected] Visit casereports.bmj.com for more articles like this and to become a Fellow
4
Bendel D, et al. BMJ Case Rep 2014. doi:10.1136/bcr-2013-202295
