COVID-19-associated pulmonary embolism: Difference between revisions

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! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Description of the underlying mechanism}}
! style="background: #4479BA; width: 200px;" |{{fontcolor|#FFF|Description of the underlying mechanism}}
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Endothelial cells|Endothelial cells dysfunction]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Endothelial cells|Endothelial cells dysfunction]]<ref name="Teuwen Geldhof Pasut Carmeliet p.">{{cite journal | last=Teuwen | first=Laure-Anne | last2=Geldhof | first2=Vincent | last3=Pasut | first3=Alessandra | last4=Carmeliet | first4=Peter | title=COVID-19: the vasculature unleashed | journal=Nature Reviews Immunology | publisher=Springer Science and Business Media LLC | date=2020-05-21 | issn=1474-1733 | doi=10.1038/s41577-020-0343-0 | page=}}</ref>
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*It has been proposed that [[endothelial cells]] contribute towards the initiation and propagation of [[ARDS]] by changing the vascular barrier permeability, increasing the chance of procoagulative state that leads to endotheliitis and infiltration of inflammatory cells in the [[Pulmonary vasculature|pulmonary vasculature.]]
*It has been proposed that [[endothelial cells]] contribute towards the initiation and propagation of [[ARDS]] by changing the vascular barrier permeability, increasing the chance of procoagulative state that leads to endotheliitis and infiltration of inflammatory cells in the [[Pulmonary vasculature|pulmonary vasculature.]]
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|Most hospitalized critically ill immobile  [[COVID-19]] patients are prone to stasis of blood flow leading to another contributor towards the [[pathogenesis]] of [[pulmonary embolism]].
|Most hospitalized critically ill immobile  [[COVID-19]] patients are prone to stasis of blood flow leading to another contributor towards the [[pathogenesis]] of [[pulmonary embolism]].
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| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Hypercoagulable state]]
| style="padding: 5px 5px; background: #DCDCDC; font-weight: bold" |[[Hypercoagulable state]]<ref name="Panigada Bottino Tagliabue Grasselli p.">{{cite journal | last=Panigada | first=Mauro | last2=Bottino | first2=Nicola | last3=Tagliabue | first3=Paola | last4=Grasselli | first4=Giacomo | last5=Novembrino | first5=Cristina | last6=Chantarangkul | first6=Veena | last7=Pesenti | first7=Antonio | last8=Peyvandi | first8=Fora | last9=Tripodi | first9=Armando | title=Hypercoagulability of COVID‐19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis | journal=Journal of Thrombosis and Haemostasis | publisher=Wiley | date=2020-04-17 | issn=1538-7933 | doi=10.1111/jth.14850 | page=}}</ref>
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Various clinical studies have reported different [[prothrombotic factors]] in patients who are critically ill and are hospitalized due to [[COVID-19|COVID-19.]] These studies report various key lab factors that play an important role in the pathogenesis of pulmonary embolism.
Various clinical studies have reported different [[prothrombotic factors]] in patients who are critically ill and are hospitalized due to [[COVID-19|COVID-19.]] These studies report various key lab factors that play an important role in the pathogenesis of pulmonary embolism.
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* Various case reports and case series report relatively high incidence of [[pulmonary embolism]] in ICU patients.
* Various case reports and case series report relatively high incidence of [[pulmonary embolism]] in ICU patients.
* The incidence of  thrombotic complications is reported to be 31 % in one study. In this study pulmonary embolism was the most common [[Thrombosis|thrombotic]] complication.
* The incidence of  thrombotic complications is reported to be 31 % in one study. In this study pulmonary embolism was the most common [[Thrombosis|thrombotic]] complication.<ref name="Klok Kruip van der Meer Arbous 2020 pp. 145–147">{{cite journal | last=Klok | first=F.A. | last2=Kruip | first2=M.J.H.A. | last3=van der Meer | first3=N.J.M. | last4=Arbous | first4=M.S. | last5=Gommers | first5=D.A.M.P.J. | last6=Kant | first6=K.M. | last7=Kaptein | first7=F.H.J. | last8=van Paassen | first8=J. | last9=Stals | first9=M.A.M. | last10=Huisman | first10=M.V. | last11=Endeman | first11=H. | title=Incidence of thrombotic complications in critically ill ICU patients with COVID-19 | journal=Thrombosis Research | publisher=Elsevier BV | volume=191 | year=2020 | issn=0049-3848 | doi=10.1016/j.thromres.2020.04.013 | pages=145–147}}</ref>
*Another study reported an overall 24% [[cumulative incidence]] of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients.  
*Another study reported an overall 24% [[cumulative incidence]] of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients. <ref name="Bompard Monnier Saab Tordjman p=2001365">{{cite journal | last=Bompard | first=Florian | last2=Monnier | first2=Hippolyte | last3=Saab | first3=Ines | last4=Tordjman | first4=Mickael | last5=Abdoul | first5=Hendy | last6=Fournier | first6=Laure | last7=Sanchez | first7=Olivier | last8=Lorut | first8=Christine | last9=Chassagnon | first9=Guillaume | last10=Revel | first10=Marie-pierre | title=Pulmonary embolism in patients with Covid-19 pneumonia | journal=European Respiratory Journal | publisher=European Respiratory Society (ERS) | date=2020-05-12 | issn=0903-1936 | doi=10.1183/13993003.01365-2020 | page=2001365}}</ref>
* In Non-ICU settings (In-patient), [[pulmonary embolism]] is reported to occur in 3% percent of patients in one study.
* In Non-ICU settings (In-patient), [[pulmonary embolism]] is reported to occur in 3% percent of patients in one study.<ref name="Middeldorp Coppens van Haaps Foppen p.">{{cite journal | last=Middeldorp | first=Saskia | last2=Coppens | first2=Michiel | last3=van Haaps | first3=Thijs F. | last4=Foppen | first4=Merijn | last5=Vlaar | first5=Alexander P. | last6=Müller | first6=Marcella C.A. | last7=Bouman | first7=Catherine C.S. | last8=Beenen | first8=Ludo F.M. | last9=Kootte | first9=Ruud S. | last10=Heijmans | first10=Jarom | last11=Smits | first11=Loek P. | last12=Bonta | first12=Peter I. | last13=van Es | first13=Nick | title=Incidence of venous thromboembolism in hospitalized patients with COVID‐19 | journal=Journal of Thrombosis and Haemostasis | publisher=Wiley | date=2020-05-05 | issn=1538-7933 | doi=10.1111/jth.14888 | page=}}</ref>


== Risk Factors ==
== Risk Factors ==
Multivariate analysis showed following risk factors that predispose a patient of COVID-19 to [[pulmonary embolism]]  
Multivariate analysis showed following risk factors that predispose a patient of COVID-19 to [[pulmonary embolism]] <ref name="Poyiadi Cormier Patel Hadied p=201955">{{cite journal | last=Poyiadi | first=Neo | last2=Cormier | first2=Peter | last3=Patel | first3=Parth Y. | last4=Hadied | first4=Mohamad O. | last5=Bhargava | first5=Pallavi | last6=Khanna | first6=Kanika | last7=Nadig | first7=Jeffrey | last8=Keimig | first8=Thomas | last9=Spizarny | first9=David | last10=Reeser | first10=Nicholas | last11=Klochko | first11=Chad | last12=Peterson | first12=Edward L. | last13=Song | first13=Thomas | title=Acute Pulmonary Embolism and COVID-19 | journal=Radiology | publisher=Radiological Society of North America (RSNA) | date=2020-05-14 | issn=0033-8419 | doi=10.1148/radiol.2020201955 | page=201955}}</ref>
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*[[Pulmonary embolism]] can present with no symptoms to [[shock]] and even [[Sudden cardiac death|sudden cardiac arrest]].
*[[Pulmonary embolism]] can present with no symptoms to [[shock]] and even [[Sudden cardiac death|sudden cardiac arrest]].
* The most common symptoms that were observed in Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial include:  
* The most common symptoms that were observed in Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial include:<ref name="Stein Beemath Matta Weg 2007 pp. 871–879">{{cite journal | last=Stein | first=Paul D. | last2=Beemath | first2=Afzal | last3=Matta | first3=Fadi | last4=Weg | first4=John G. | last5=Yusen | first5=Roger D. | last6=Hales | first6=Charles A. | last7=Hull | first7=Russell D. | last8=Leeper | first8=Kenneth V. | last9=Sostman | first9=H. Dirk | last10=Tapson | first10=Victor F. | last11=Buckley | first11=John D. | last12=Gottschalk | first12=Alexander | last13=Goodman | first13=Lawrence R. | last14=Wakefied | first14=Thomas W. | last15=Woodard | first15=Pamela K. | title=Clinical Characteristics of Patients with Acute Pulmonary Embolism: Data from PIOPED II | journal=The American Journal of Medicine | publisher=Elsevier BV | volume=120 | issue=10 | year=2007 | issn=0002-9343 | doi=10.1016/j.amjmed.2007.03.024 | pages=871–879}}</ref>
**[[Dyspnea]] that is sudden in onset at rest or exertion (73%)
**[[Dyspnea]] that is sudden in onset at rest or exertion (73%)
**[[Pleuritic pain]] (44%)
**[[Pleuritic pain]] (44%)
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===== Imaging studies =====
===== Imaging studies =====


*Prompt diagnosis of PE in COVID-19 patient is difficult in this regard that various symptoms of [[COVID-19]] overlap with that of [[pulmonary embolism]]. American Society of Hematology provides the following guidelines regarding the diagnosis of pulmonary embolism:
*Prompt diagnosis of PE in COVID-19 patient is difficult in this regard that various symptoms of [[COVID-19]] overlap with that of [[pulmonary embolism]]. American Society of Hematology provides the following guidelines regarding the diagnosis of pulmonary embolism:<ref name="Hematology.org 2020">{{cite web | title=COVID-19 and Pulmonary Embolism | website=Hematology.org | date=2020-05-18 | url=https://www.hematology.org:443/covid-19/covid-19-and-pulmonary-embolism | access-date=2020-06-23}}</ref>
** Normal [[d-dimers]] level in a patient with low to moderate [[Pretest probability of DVT|pretest probability]] is sufficient to rule out the diagnosis of PE. [[D-dimers|D-dimers level]] is usually elevated in COVID-19 patients. This is not applicable to a patient with a high pretest probability.
** Normal [[d-dimers]] level in a patient with low to moderate [[Pretest probability of DVT|pretest probability]] is sufficient to rule out the diagnosis of PE. [[D-dimers|D-dimers level]] is usually elevated in COVID-19 patients. This is not applicable to a patient with a high pretest probability.
** Inpatient with suspected PE with symptoms like [[hypotension]], [[tachycardia]], and sudden drop in [[oxygen saturation]] with a high pretest probability of PE, computed [[tomography]] with [[pulmonary angiography]] is used for the diagnosis. Contraindication to the use of [[CT pulmonary angiogram|CTPA]] warrants investigation with [[Ventilation/perfusion scan|ventilation/perfusion scan.]]
** Inpatient with suspected PE with symptoms like [[hypotension]], [[tachycardia]], and sudden drop in [[oxygen saturation]] with a high pretest probability of PE, computed [[tomography]] with [[pulmonary angiography]] is used for the diagnosis. Contraindication to the use of [[CT pulmonary angiogram|CTPA]] warrants investigation with [[Ventilation/perfusion scan|ventilation/perfusion scan.]]
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===== Laboratory findings =====
===== Laboratory findings =====
Lab findings of different case studies of patients having pulmonary embolism due to COVID-19 are given as
Lab findings of different case studies of patients having pulmonary embolism due to COVID-19 are given as <ref name="Bikdeli Madhavan Jimenez Chuich 2020 pp. 2950–2973">{{cite journal | last=Bikdeli | first=Behnood | last2=Madhavan | first2=Mahesh V. | last3=Jimenez | first3=David | last4=Chuich | first4=Taylor | last5=Dreyfus | first5=Isaac | last6=Driggin | first6=Elissa | last7=Nigoghossian | first7=Caroline Der | last8=Ageno | first8=Walter | last9=Madjid | first9=Mohammad | last10=Guo | first10=Yutao | last11=Tang | first11=Liang V. | last12=Hu | first12=Yu | last13=Giri | first13=Jay | last14=Cushman | first14=Mary | last15=Quéré | first15=Isabelle | last16=Dimakakos | first16=Evangelos P. | last17=Gibson | first17=C. Michael | last18=Lippi | first18=Giuseppe | last19=Favaloro | first19=Emmanuel J. | last20=Fareed | first20=Jawed | last21=Caprini | first21=Joseph A. | last22=Tafur | first22=Alfonso J. | last23=Burton | first23=John R. | last24=Francese | first24=Dominic P. | last25=Wang | first25=Elizabeth Y. | last26=Falanga | first26=Anna | last27=McLintock | first27=Claire | last28=Hunt | first28=Beverley J. | last29=Spyropoulos | first29=Alex C. | last30=Barnes | first30=Geoffrey D. | last31=Eikelboom | first31=John W. | last32=Weinberg | first32=Ido | last33=Schulman | first33=Sam | last34=Carrier | first34=Marc | last35=Piazza | first35=Gregory | last36=Beckman | first36=Joshua A. | last37=Steg | first37=P. Gabriel | last38=Stone | first38=Gregg W. | last39=Rosenkranz | first39=Stephan | last40=Goldhaber | first40=Samuel Z. | last41=Parikh | first41=Sahil A. | last42=Monreal | first42=Manuel | last43=Krumholz | first43=Harlan M. | last44=Konstantinides | first44=Stavros V. | last45=Weitz | first45=Jeffrey I. | last46=Lip | first46=Gregory Y.H. | title=COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up | journal=Journal of the American College of Cardiology | publisher=Elsevier BV | volume=75 | issue=23 | year=2020 | issn=0735-1097 | doi=10.1016/j.jacc.2020.04.031 | pages=2950–2973}}</ref>


* Elevated [[D-dimer|d-dimers]]
* Elevated [[D-dimer|d-dimers]]
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== References ==
 
 
<br />
<references />
<references />

Revision as of 10:39, 25 June 2020

Overview

  • In May 2020, various autopsies studies revealed pulmonary embolism to be the common cause of death in COVID-19 infected patients.
  • These patients in their mid-70s had preexisting medical conditions such as cardiac diseases, hypertension, diabetes, and obesity.
  • These studies highlight the role of hypercoagulability as the main contributor to the fatality in these patients.
  • Various studies have described Virchow's triad to be the main component of the hypercoagulable state in these patients.

Historical Perspective

Classification

Pathophysiology


  • As data on COVID-19 has been incomplete and evolving, the pathogenesis of pulmonary embolism has not yet been completely understood. Various contributors to the pathogenesis of pulmonary embolism in these patients are listed in the table below:
Pathology Description of the underlying mechanism
Endothelial cells dysfunction[1]
  • It has been proposed that endothelial cells contribute towards the initiation and propagation of ARDS by changing the vascular barrier permeability, increasing the chance of procoagulative state that leads to endotheliitis and infiltration of inflammatory cells in the pulmonary vasculature.
  • It has been proposed that COVID-19 can directly affect endothelial cells leading to widespread endotheliitis. SARS-CoV-2 also binds to the ACE2 receptors which alter the activity of ACE2.
  • Reduced ACE2 activity leads to activation of the kallikrein-bradykinin pathway, which increases vascular permeability.
  • The activated neutrophils migrate towards the pulmonary endothelial cells and produce cytotoxic mediators including reactive oxygen species.
Stasis Most hospitalized critically ill immobile COVID-19 patients are prone to stasis of blood flow leading to another contributor towards the pathogenesis of pulmonary embolism.
Hypercoagulable state[2]

Various clinical studies have reported different prothrombotic factors in patients who are critically ill and are hospitalized due to COVID-19. These studies report various key lab factors that play an important role in the pathogenesis of pulmonary embolism.


Causes

Differentiating Pulmonary Embolism from other Diseases

Epidemiology and demographics

  • Various case reports and case series report relatively high incidence of pulmonary embolism in ICU patients.
  • The incidence of thrombotic complications is reported to be 31 % in one study. In this study pulmonary embolism was the most common thrombotic complication.[3]
  • Another study reported an overall 24% cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30–70%) in ICU and 18% (12–27%) in other patients. [4]
  • In Non-ICU settings (In-patient), pulmonary embolism is reported to occur in 3% percent of patients in one study.[5]

Risk Factors

Multivariate analysis showed following risk factors that predispose a patient of COVID-19 to pulmonary embolism [6]

Natural History,Complications and Prognosis

Diagnosis

History and Symptoms

  • Pulmonary embolism can present with no symptoms to shock and even sudden cardiac arrest.
  • The most common symptoms that were observed in Prospective Investigation of Pulmonary Embolism Diagnosis II (PIOPED II) trial include:[7]
    • Dyspnea that is sudden in onset at rest or exertion (73%)
    • Pleuritic pain (44%)
    • Calf or thigh pain (44%)
    • Calf or thigh swelling (41%)
    • Cough (34%)
Imaging studies
Right-sided segmental and subsegmental pulmonary arterial filling defects (yellow arrows) in keeping with acute distal pulmonary emboli. Source: Dr Gianluca Martinellihttps://radiopaedia.org/cases/76817
Laboratory findings

Lab findings of different case studies of patients having pulmonary embolism due to COVID-19 are given as [9]

Treatment

  • Different treatment strategies for COVID-19 patients suffering from pulmonary embolism are given in the table below:
Different treatment options Details
Prophylaxis All hospitalized patients with COVID 19 should get proper venous thromboembolism prophylaxis in the absence of any contraindication of anticoagulation.
  • In ICU setting, empiric use of intermediate or therapeutic dose anticoagulation should be instituted.
  • In a non-ICU setting, all hospitalized patients should be treated with prophylactic low dose molecular weight heparin.
Acute Pulmonary embolism
Outpatient treatment[8]
  • Critically ill patients that have recovered from COVID-19 and had a documented VTE are usually given a minimum of 3 months of anticoagulation.
  • Patients not admitted to hospitals but at risk of VTE, such as prior VTE episode, recent surgery, prolonged immobilization are usually given a prophylactic dose of Rivaroxaban 10 mg daily for 31 days or 39 days.



  1. ↑ Teuwen, Laure-Anne; Geldhof, Vincent; Pasut, Alessandra; Carmeliet, Peter (2020-05-21). "COVID-19: the vasculature unleashed". Nature Reviews Immunology. Springer Science and Business Media LLC. doi:10.1038/s41577-020-0343-0. ISSN 1474-1733.
  2. ↑ Panigada, Mauro; Bottino, Nicola; Tagliabue, Paola; Grasselli, Giacomo; Novembrino, Cristina; Chantarangkul, Veena; Pesenti, Antonio; Peyvandi, Fora; Tripodi, Armando (2020-04-17). "Hypercoagulability of COVID‐19 patients in Intensive Care Unit. A Report of Thromboelastography Findings and other Parameters of Hemostasis". Journal of Thrombosis and Haemostasis. Wiley. doi:10.1111/jth.14850. ISSN 1538-7933.
  3. ↑ Klok, F.A.; Kruip, M.J.H.A.; van der Meer, N.J.M.; Arbous, M.S.; Gommers, D.A.M.P.J.; Kant, K.M.; Kaptein, F.H.J.; van Paassen, J.; Stals, M.A.M.; Huisman, M.V.; Endeman, H. (2020). "Incidence of thrombotic complications in critically ill ICU patients with COVID-19". Thrombosis Research. Elsevier BV. 191: 145–147. doi:10.1016/j.thromres.2020.04.013. ISSN 0049-3848.
  4. ↑ Bompard, Florian; Monnier, Hippolyte; Saab, Ines; Tordjman, Mickael; Abdoul, Hendy; Fournier, Laure; Sanchez, Olivier; Lorut, Christine; Chassagnon, Guillaume; Revel, Marie-pierre (2020-05-12). "Pulmonary embolism in patients with Covid-19 pneumonia". European Respiratory Journal. European Respiratory Society (ERS): 2001365. doi:10.1183/13993003.01365-2020. ISSN 0903-1936.
  5. ↑ Middeldorp, Saskia; Coppens, Michiel; van Haaps, Thijs F.; Foppen, Merijn; Vlaar, Alexander P.; Müller, Marcella C.A.; Bouman, Catherine C.S.; Beenen, Ludo F.M.; Kootte, Ruud S.; Heijmans, Jarom; Smits, Loek P.; Bonta, Peter I.; van Es, Nick (2020-05-05). "Incidence of venous thromboembolism in hospitalized patients with COVID‐19". Journal of Thrombosis and Haemostasis. Wiley. doi:10.1111/jth.14888. ISSN 1538-7933.
  6. ↑ Poyiadi, Neo; Cormier, Peter; Patel, Parth Y.; Hadied, Mohamad O.; Bhargava, Pallavi; Khanna, Kanika; Nadig, Jeffrey; Keimig, Thomas; Spizarny, David; Reeser, Nicholas; Klochko, Chad; Peterson, Edward L.; Song, Thomas (2020-05-14). "Acute Pulmonary Embolism and COVID-19". Radiology. Radiological Society of North America (RSNA): 201955. doi:10.1148/radiol.2020201955. ISSN 0033-8419.
  7. ↑ Stein, Paul D.; Beemath, Afzal; Matta, Fadi; Weg, John G.; Yusen, Roger D.; Hales, Charles A.; Hull, Russell D.; Leeper, Kenneth V.; Sostman, H. Dirk; Tapson, Victor F.; Buckley, John D.; Gottschalk, Alexander; Goodman, Lawrence R.; Wakefied, Thomas W.; Woodard, Pamela K. (2007). "Clinical Characteristics of Patients with Acute Pulmonary Embolism: Data from PIOPED II". The American Journal of Medicine. Elsevier BV. 120 (10): 871–879. doi:10.1016/j.amjmed.2007.03.024. ISSN 0002-9343.
  8. ↑ 8.0 8.1 "COVID-19 and Pulmonary Embolism". Hematology.org. 2020-05-18. Retrieved 2020-06-23.
  9. ↑ Bikdeli, Behnood; Madhavan, Mahesh V.; Jimenez, David; Chuich, Taylor; Dreyfus, Isaac; Driggin, Elissa; Nigoghossian, Caroline Der; Ageno, Walter; Madjid, Mohammad; Guo, Yutao; Tang, Liang V.; Hu, Yu; Giri, Jay; Cushman, Mary; Quéré, Isabelle; Dimakakos, Evangelos P.; Gibson, C. Michael; Lippi, Giuseppe; Favaloro, Emmanuel J.; Fareed, Jawed; Caprini, Joseph A.; Tafur, Alfonso J.; Burton, John R.; Francese, Dominic P.; Wang, Elizabeth Y.; Falanga, Anna; McLintock, Claire; Hunt, Beverley J.; Spyropoulos, Alex C.; Barnes, Geoffrey D.; Eikelboom, John W.; Weinberg, Ido; Schulman, Sam; Carrier, Marc; Piazza, Gregory; Beckman, Joshua A.; Steg, P. Gabriel; Stone, Gregg W.; Rosenkranz, Stephan; Goldhaber, Samuel Z.; Parikh, Sahil A.; Monreal, Manuel; Krumholz, Harlan M.; Konstantinides, Stavros V.; Weitz, Jeffrey I.; Lip, Gregory Y.H. (2020). "COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up". Journal of the American College of Cardiology. Elsevier BV. 75 (23): 2950–2973. doi:10.1016/j.jacc.2020.04.031. ISSN 0735-1097.
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