Pulmonary embolus

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A commonly lethal result of (usually) venous thromboembolic disease

Pulmonary embolism (PE) can be any form of embolism to the pulmonary arterial tree, such as bone marrow after trauma, but is most commonly thromboembolism. Even if caused by thromboembolism it has a slightly different epidemiology from deep vein thrombosis[1].

Contents

Incidence

Depends on sub-population. See thromboprophylaxis for details of significant risk factors including surgery and several medical conditions.

Recognition

Massive thrombus occluding the pulmonary artery.
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  1. Many death certificates saying "myocardial infarction" are suspected to have been caused by a promptly fatal large PE. Without an autopsy it is hard to know.
  2. Only about 20% of those suspected to have had a PE on clinical grounds will have objective evidence confirming this on investigation.

A sudden collapse with poor cardiac output - dizziness and weakness - followed by considerable recovery is a classic presentation of a medium-sized PE. At this point the patient may be saveable, although the risk of a second PE in the next few minutes; during establishment of anticoagulation, or before lysis of the thrombosis has completed is high. The clot, having been swept into the pulmonary artery or arteries and largely blocked cardiac output is packed further into a subset of the arteries, uncovering others and allowing blood flow and gaseous exchange to resume. This sequence of events is less obvious from the history shortly afterward, and particularly in the community needs to be raised in the doctor's consciousness. One audit of community sudden death from PE noted that in those few seen in A&E within 48 hours previously with symptoms that retrospectively might have been due to a "silent" PE and discharged a hint towards the correct diagnosis that was overlooked was low pulse oximeter readings in those with no previous history of respiratory disease.

Diagnosis

  • Consider risk factors to gauge pre-test probability. There are several clinical scoring systems in use, which in combination with D-dimer and/or imaging can reliably exclude thrombotic pulmonary embolism. These scores are useful for inexperienced doctors to use. It is important for clinicians to recognise that such scores are based on common risk factors, and less common but known associations such as specific drugs (eg combined contraceptives, strontium ranelate, major tranquillisers) or specific disease (eg autoimmune disease) may not be considered in a score. Several comparisons between the scores have been published and there is little doubt that patient population characteristics determine which score is best.
    • Wells' (Canadian) score[2] is well validated[3] although its use of negative scores for alternative diagnoses has been critisised when the clinical priority is to exclude PE [4].It is easy to use and may be better at risk stratification than the Geneva score[5][6]
    • Geneva score[7][8] Validated best in outpatients.
    • Miniati rule (Pisa model)[9]
    • Charlotte rule based on Bayesian network analysis[10]

Interestingly the unstructured clinical estimate of low pretest probability for PE by an experienced clinician compares favorably with clinical scoring rules[11][12][13] Note:last two references are from same authors

  • D-dimer - for exclusion rather than diagnosis
  • CXR - Often normal, but occasionally may show:
  • V/Q scan (ventilation-perfusion lung scan) -Positive predictive value is 85 to 88% for a high probability scan. Negative predictive value with undectable D-dimer is over 99%. However prevalence of PE with a non-diagnostic scan is 20 to 24%[14]
  • Pulmonary angiography remains the gold standard for segmental pulmonary embolism but no longer for subsegmental PE[14]
  • CTPA - positive predictive value is >95% for helical spiral CT[14]. Problematically not all CT scanners are as sensitive and specific as each other and human error is possible(<4% in experienced reporters), increasing with time pressure and anatomical and technical complexity and decreasing with reporters experience[15]. Computer-assisted detection can increase sensitivity to almost 100% but drops specificity by about 2%[15]. It is possible to reduce the need to do a helical spiral CT angiogram by a combination of clinical assessment, D-dimer, and compression U/S by 40 to 50%.[16]. As contrast-enhanced pulmonary multidetector CT angiography can show all clinically relevant PE it can replace both the V/Q scan and pulmonary angiography. Indeed front door clinicians find it often shows an alternative diagnosis when it excludes PE which is less the case with other imaging. Helical spiral CT delivers a higher dose of radiation to the mother but a lower dose to the fetus than V/Q lung scanning.

Treatment

Following a single pulmonary embolus (PE) full anticoagulation should be started urgently (there is evidence of about a four fold survival benefit for fully therapeutic treatment within a day of admission in those with high clinical probability)[17] and continued for a period of the order of six months. There are certain situations where it may be continued for life, for example if the patient also has atrial fibrillation or past thromboembolic disease. Anything other than permanent anticoagulation after a recurrent PE would need a very clear reason and explanation in the notes. This is not to say that there are not situations where continuing anticoagulation is more dangerous than ceasing it after a period.

Large or saddle pulmonary emboli may be treated if expertise is readily available surgically with pulmonary embolectomy or by direct catheter breakup on angiography.

In peri-arrest and unstable patients with large PE, thrombolysis is the recommended option based on meta-analysis, although direct supporting evidence for this approach is understandably difficult to collect[18].

Occasionally vena cava filters may have a role. Used alone they may prevent fatal PE but could clog up and do not prevent peripheral complications of deep vein thrombosis.

Occasionally PE may be detected incidentally on CTs done for other reasons. Certainly in cancer patients incidental segmental PEs or above should be treated on present evidence[19].

Isolated Subsegmental Pulmonary Embolism

Treatment is controversial as repeated studies have shown negligible survival impact and some are detected incidentally. Certainly the risk of bleeding seems greater than PE events prevented[20], including in cancer patients[19]. A recent review suggested it was safe to withhold long term treatment if:[21]:

  1. Doppler U/S of calf veins was negative initially and at 1 week
  2. Respiratory reserve was good
  3. Any major risk factor for PE was transient and no longer present
  4. There is no history of central venous catheterization or atrial fibrillation

Prognosis

  • Remarkably good once anti-coagulated and clinically improving. Mortality and morbidity tends to be dictated by individual patient risk of bleeding or underlying pathology.
  • You can get into clinically no win situations with tumours that block vena cava filters or cause hemorrhage as well as a pro-thrombotic state.

Avoidance and Prophylaxis

Prophylaxis is imperfectly applied in many clinical situations by physicians, patients and those involved in funding the necessary resources. Often low risk patients such as the young are prioritised rather than high risk elderly patients and the length or type of thromboprophylaxis is dictated by convenience rather than evidence. There is little doubt that increasingly in all health systems as patients are returned home more rapidly and less recovered, prophylaxis should be expected to be needed in the community. Until recently NHS prescribing arrangements denied the supply of suitable heparin formulations by GPs but this has now changed. There is evidence for between 4 to 6 weeks thromboprophylaxis after an ever increasing number of surgical interventions. The historic view that people mobilise more at at home than in hospital so are at less risk actually depended on patient circumstances and has in fact been shown to be irrelevant.

External links

References

  1. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet. 2012 Apr 5.(Epub ahead of print) (Link to article – subscription may be required.)
  2. Wells PS, Anderson DR, Rodger M, Ginsberg JS, Kearon C, Gent M, et al. Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer. Thrombosis and haemostasis. 2000;83:416-20.
  3. Wolf SJ, McCubbin TR, Feldhaus KM, Faragher JP, Adcock DM. Prospective validation of Wells Criteria in the evaluation of patients with suspected pulmonary embolism. Annals of emergency medicine. 2004;44:503-10. (Direct link – subscription may be required.)
  4. Michiels JJ, Gadisseur A, van der Planken M, Schroyens W, De Maeseneer M, Hermsen JT, et al. Different accuracies of rapid enzyme-linked immunosorbent, turbidimetric, and agglutination d-dimer assays for thrombosis exclusion: impact on diagnostic work-ups of outpatients with suspected deep vein thrombosis and pulmonary embolism. Seminars in thrombosis and hemostasis. 2006;32:678-93. (Direct link – subscription may be required.)
  5. Moores LK, Collen JF, Woods KM, Shorr AF. Practical utility of clinical prediction rules for suspected acute pulmonary embolism in a large academic institution. Thrombosis research. 2004;113:1-6. (Direct link – subscription may be required.)
  6. Ulukavak Ciftçi T, Köktürk N, Demir N, Oğuzülgen KI, Ekim N Comparison of three clinical prediction rules among patients with suspected pulmonary embolism. Tuberk Toraks. 2005;53:252-8.
  7. Chagnon I, Bounameaux H, Aujesky D, Roy PM, Gourdier AL, Cornuz J, et al. Comparison of two clinical prediction rules and implicit assessment among patients with suspected pulmonary embolism. The American journal of medicine. 2002;113:269-75.
  8. Le Gal G, Righini M, Roy PM, Sanchez O, Aujesky D, Bounameaux H, et al. Prediction of pulmonary embolism in the emergency department: the revised Geneva score. Annals of internal medicine. 2006;144:165-71.
  9. Miniati M, Pistolesi M. Assessing the clinical probability of pulmonary embolism. The quarterly journal of nuclear medicine : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR). 2001;45:287-93.
  10. Kline JA, Novobilski AJ, Kabrhel C, Richman PB, Courtney DM. Derivation and validation of a Bayesian network to predict pretest probability of venous thromboembolism. Annals of emergency medicine. 2005;45:282-90. (Direct link – subscription may be required.)
  11. Chunilal SD, Eikelboom JW, Attia J, Miniati M, Panju AA, Simel DL, et al. Does this patient have pulmonary embolism? JAMA : the journal of the American Medical Association. 2003;290:2849-58. (Direct link – subscription may be required.)
  12. Runyon MS, Webb WB, Jones AE, Kline JA. Comparison of the unstructured clinician estimate of pretest probability for pulmonary embolism to the Canadian score and the Charlotte rule: a prospective observational study. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2005;12:587-93. (Direct link – subscription may be required.)
  13. Kline JA, Runyon MS, Webb WB, Jones AE, Mitchell AM. Prospective study of the diagnostic accuracy of the simplify D-dimer assay for pulmonary embolism in emergency department patients. Chest. 2006;129:1417-23. (Direct link – subscription may be required.)
  14. a b c Michiels JJ, Hoogsteden H, Pattynama PM. Non-invasive diagnosis of pulmonary embolism, anno 2005. Acta chirurgica Belgica. 2005;105:26-34.
  15. a b Dewailly M, Rémy-Jardin M, Duhamel A, Faivre JB, Pontana F, Deken V, Bakai AM, Remy J. Computer-aided detection of acute pulmonary embolism with 64-slice multi-detector row computed tomography: impact of the scanning conditions and overall image quality in the detection of peripheral clots. Journal of computer assisted tomography. 2010 Jan; 34(1):23-30.(Link to article – subscription may be required.)
  16. Michiels JJ, Gadisseur A, van der Planken M, Schroyens W, De Maeseneer M, Hermsen JT, et al. Screening for deep vein thrombosis and pulmonary embolism in outpatients with suspected DVT or PE by the sequential use of clinical score: a sensitive quantitative D-dimer test and noninvasive diagnostic tools. Seminars in vascular medicine. 2005;5:351-64. (Direct link – subscription may be required.)
  17. Smith SB, Geske JB, Maguire JM, Zane NA, Carter RE, Morgenthaler TI. Early anticoagulation is associated with reduced mortality for acute pulmonary embolism. Chest. 2010 Jun; 137(6):1382-90.(Link to article – subscription may be required.)
  18. Wan S, Quinlan DJ, Agnelli G, Eikelboom JW. Thrombolysis compared with heparin for the initial treatment of pulmonary embolism: a meta-analysis of the randomized controlled trials. Circulation. 2004 Aug 10; 110(6):744-9.(Link to article – subscription may be required.)
  19. a b O'Connell C, Razavi P, Ghalichi M, Boyle S, Vasan S, Mark L, Caton A, Duddalwar V, Boswell W, Grabow K, Liebman HA. Unsuspected pulmonary emboli adversely impact survival in patients with cancer undergoing routine staging multi-row detector computed tomography scanning. Journal of thrombosis and haemostasis : JTH. 2011 Feb; 9(2):305-11.(Link to article – subscription may be required.)
  20. Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thrombosis research. 2010 Oct; 126(4):e266-70.(Link to article – subscription may be required.)
  21. Stein PD, Goodman LR, Hull RD, Dalen JE, Matta F. Diagnosis and Management of Isolated Subsegmental Pulmonary Embolism: Review and Assessment of the Options. Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2011 Sep 23.(Epub ahead of print) (Link to article – subscription may be required.)