Joseph Abraham Kavian, Cecilia Becattini, Ran Schwarzkopf.
Response/Recommendation: Clot location, detected by imaging in patients presenting with pulmonary embolism (PE), does not serve as a significant independent factor to influence the risk of death and therefore the type of anticoagulation treatment to be administered. Significant predictors of poor outcomes in PE are hemodynamic instability and right ventricular strain, as opposed to clot location. Nonetheless, the decision to initiate more invasive and direct treatment, such as through thrombolysis or embolectomy, may be influenced by the size and location of an embolus. Central and larger clots may be more approachable by invasive interventions, yet further exploration of a patient’s clinical picture, beyond mere analysis of clot location, is more crucial in such treatment decisions.
Strength of Recommendation: Moderate.
Rationale: Treatment options for PE include anticoagulation therapy, thrombolytic therapy, and invasive interventions such as percutaneous and/or surgical clot removal1. Anticoagulation treatments carry the risks of bleeding, thrombocytopenia, osteoporosis, skin necrosis, and potential teratogenicity2. Clot location, as seen on imaging, plays an important role in determining overall treatment approach such as initiating invasive intervention or systemic anticoagulation, but does not seem to be a major factor that influences the type of anticoagulation treatment once that has been initiated2. Size and location of clot have not been found to correlate with clinical signs, symptoms, or severity of hypoxia3. In deciding on anticoagulant medication options, each carries its disadvantages and advantages, with the ultimate decision on treatment depending on provider preference and patient scenario4. The severity and manifestation of PE can range from significantly occlusive large central emboli to scattered and small clots throughout the pulmonary vasculature. The decision to treat small pulmonary emboli, however, especially those discovered incidentally, is subject to debate and controversy5.
Studies have noted an increase in frequency of PE detection, yet the 3-month risk of venous thromboembolism (VTE) in untreated patients with suspected PE using multi-detector versus single detector computed tomography pulmonary angiography (CTPA) did not differ2,6,7. These findings have led several providers to conclude that anticoagulation treatment of isolated subsegmental pulmonary emboli is not warranted, and such small emboli may be clinically insignificant2. Yet, supporters of this view would propose that anticoagulation treatment should still be initiated in any patient presenting with poor pulmonary reserve, concurrent presence of deep venous thrombosis, history of recurrent PE, or presence of any genetic thrombophilia or hypofibrinolysis2. Nonetheless, studies have also found that patients with subsegmental PE have similar clinical outcomes to those with more central PE in terms of recurrent VTE, bleeding complications, and mortality6,7. Due to the indirect evidence surrounding this debate, it can be reasonably concluded that the decision to treat isolated and incidental small clots, such as subsegmental emboli, should not depend on clot location as seen by imaging; rather, such a decision should depend on a more thorough analysis of each patient in terms of clinical status and potential risk factors5,6,8.
In determining the feasibility and effectiveness of more aggressive interventions such as percutaneous thrombectomy or surgical embolectomy, clot size and location are significant in that more central and large clots are more amenable to thrombectomy. Thrombolysis may be indicated in patients who present with shock and hypotension or display signs of right ventricular dysfunction or myocardial injury based on biochemical markers or imaging9–12. Here, location may be a weighed as a factor in that central catheter infusions are more likely to be effective in cases of diffuse and equally distributed clot burden, whereas pulse spray catheterization may be more favorable in instances of large, central emboli11.
1. Goldhaber SZ. Advanced treatment strategies for acute pulmonary embolism, including thrombolysis and embolectomy. J Thromb Haemost. 2009;7 Suppl 1:322-327. doi:10.1111/j.1538-7836.2009.03415.x
2. Tornetta P, Bogdan Y. Pulmonary embolism in orthopaedic patients: diagnosis and management. J Am Acad Orthop Surg. 2012;20(9):586-595. doi:10.5435/JAAOS-20-09-586
3. Pulido L, Grossman S, Smith EB, et al. Clinical presentation of pulmonary embolus after total joint arthroplasty: do size and location of embolus matter? Am J Orthop (Belle Mead NJ). 2010;39(4):185-189.
4. Robertson L, Jones LE. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for the initial treatment of venous thromboembolism. Cochrane Database Syst Rev. 2017;2:CD001100. doi:10.1002/14651858.CD001100.pub4
5. Yoo HHB, Queluz THAT, El Dib R. Anticoagulant treatment for subsegmental pulmonary embolism. Cochrane Database Syst Rev. 2014;(4):CD010222. doi:10.1002/14651858.CD010222.pub2
6. Peiman S, Abbasi M, Allameh SF, Asadi Gharabaghi M, Abtahi H, Safavi E. Subsegmental pulmonary embolism: A narrative review. Thromb Res. 2016;138:55-60. doi:10.1016/j.thromres.2015.12.003
7. den Exter PL, van Es J, Klok FA, et al. Risk profile and clinical outcome of symptomatic subsegmental acute pulmonary embolism. Blood. 2013;122(7):1144-1149; quiz 1329. doi:10.1182/blood-2013-04-497545
8. Penaloza A, Roy P-M, Kline J. Risk stratification and treatment strategy of pulmonary embolism. Curr Opin Crit Care. 2012;18(4):318-325. doi:10.1097/MCC.0b013e32835444bc
9. Wood KE. Major pulmonary embolism: review of a pathophysiologic approach to the golden hour of hemodynamically significant pulmonary embolism. Chest. 2002;121(3):877-905. doi:10.1378/chest.121.3.877
10. Patra S, Agrawal N, Manjunath CN, et al. Thrombolytic therapy in the treatment of acute sub-massive pulmonary embolism: a prospective observational study. Blood Coagul Fibrinolysis. 2014;25(2):167-171. doi:10.1097/MBC.0000000000000015
11. Teleb M, Porres-Aguilar M, Anaya-Ayala JE, Rodriguez-Castro C, Porres-Muñoz M, Mukherjee D. Potential role of systemic thrombolysis in acute submassive intermediate risk pulmonary embolism: review and future perspectives. Ther Adv Cardiovasc Dis. 2016;10(2):103-110. doi:10.1177/1753944716630694
12. Mohan B, Tandon R, Bansal R, et al. Determinants of in-hospital clinical outcome in patients with sub-massive pulmonary embolism. Indian Heart J. 2018;70 Suppl 3:S90-S95. doi:10.1016/j.ihj.2018.06.008