Thrombosis Research 202 (2021) 162–169
Contents lists available at ScienceDirect
Thrombosis Research
journal homepage: www.elsevier.com/locate/thromres
Pulmonary infarction in acute pulmonary embolism
F.H.J. Kaptein a, L.J.M. Kroft b, G. Hammerschlag c, M.K. Ninaber d, M.P. Bauer e, M.
V. Huisman a, F.A. Klok a, *
a
Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
b
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
c
Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, Australia
d
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
e
Department of Medicine – Acute Medicine, Leiden University Medical Center, Leiden, the Netherlands
A R T I C L E I N F O A B S T R A C T
Keywords: Pulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage
Pulmonary embolism and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute pulmonary embolism (PE),
Pulmonary infarction with a reported incidence of around 30%. Following an occlusion of the pulmonary artery, the bronchial arteries
Hemorrhage
are recruited as primary source of perfusion of the pulmonary capillaries. The relatively higher blood pressure in
Diagnostic imaging
Prognosis
the bronchial circulation causes an increase in the capillary blood flow, leading to extravasation of erythrocytes
(i.e. alveolar hemorrhage). If this hemorrhage cannot be resorbed, it results in tissue necrosis and infarction.
Different definitions of pulmonary infarction are used in literature (clinical, radiological and histological),
although the diagnosis is nowadays mostly based on radiological characteristics. Notably, the infarcted area is
only replaced by a fibrotic scar over a period of months. Hence and formally, the diagnosis of pulmonary
infarction cannot be confirmed upon diagnosis of acute PE. Little is known of the impact and relevance of
pulmonary infarction in acute PE, and whether specific management strategies should be applied to prevent and/
or treat complications such as pain, pneumonia or post-PE syndrome. In this review we will summarize current
knowledge on the pathophysiology, epidemiology, diagnosis and prognosis of pulmonary infarction in the setting
of acute PE. We highlight the need for dedicated studies to overcome the current knowledge gaps.
1. Introduction if at all. Nevertheless, recognizing pulmonary infarction is clinically
relevant, both during the diagnostic phase as well as well as for making
Pulmonary infarction results from occlusion of the distal pulmonary management decisions. For instance, patients with pulmonary infarction
arteries leading to ischemia, hemorrhage and ultimately necrosis of the secondary to acute PE may be more likely to present with pleuritic chest
lung parenchyma. It is most often caused by acute pulmonary embolism pain and fever, and may more often require hospitalization and targeted
(PE), a frequently occurring and potentially life-threatening disease. (1) (intravenous) analgesic drugs to manage pain.
The reported annual incidence of PE varies between 75 and 269 cases In this review we will summarize current knowledge on the patho
per 100,000 persons, and mortality rates as high as 28% have been physiology, epidemiology, diagnosis and prognosis of pulmonary
described. (1–4) Although the dual blood supply to the lungs, i.e. the infarction in the setting of acute PE (Fig. 1).
pulmonary and the bronchial circulation, is thought to be protective
against pulmonary ischemia, pulmonary infarction can be found in 10 to 1.1. Pathophysiology
50% of all patients with PE. (5) This wide range is the result of the
difference in definition of pulmonary infarction used in literature, which The lungs receive deoxygenated blood from the pulmonary arteries
varies from pulmonary infarction as a clinical syndrome to a radiological (low pressure, high flow circulation) and oxygenated blood from the
finding or a histological phenomenon. Literature on this complication is bronchial arteries (at systemic pressure, i.e. 6 times that of the pulmo
limited, and pulmonary infarction is scarcely addressed in PE guidelines, nary arteries). The function of the pulmonary circulation is mainly gas
Abbreviations: PE, pulmonary embolism; CTPA, computed tomography pulmonary angiography.
* Corresponding author at: Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
E-mail address: (F.A. Klok).
https://doi.org/10.1016/j.thromres.2021.03.022
Received 27 January 2021; Received in revised form 5 March 2021; Accepted 24 March 2021
Available online 1 April 2021
0049-3848/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
, F.H.J. Kaptein et al. Thrombosis Research 202 (2021) 162–169
exchange, whereas the bronchial circulation supplies the bronchial to impaired resolution of alveolar hemorrhage and thus progression to
walls, the visceral pleura and the lung parenchyma with oxygenated local necrosis. (10–14)
blood (next to direct passive diffusion of oxygen in the latter). (6) This Dalen et al. showed that emboli in distal pulmonary branches were
dual blood supply has been thought to be protective against ischemic more likely to cause pulmonary infarction than more extensive and/or
injuries of the lungs. Animal models have shown that lung tissue may central obstructions. (11) Virchow described that after ligating a main
stay viable after ligation of the supplying pulmonary artery, where pulmonary artery, the collateral flow from the bronchial circulation
perfusion is maintained by the bronchial circulation: the bronchial ar enters the pulmonary circulation distal to the site of obstruction (as they
teries undergo smooth muscle wall hypertrophy and dilate to direct anastomose at the pre-pulmonary-capillary level), supporting Dalen’s
more oxygenated blood to ischemic lung tissue, and eventually increase observation. (9) In a central pulmonary artery occlusion, the high-
in number. (7,8) Even so, obstruction of a pulmonary artery by acute PE pressure inflow from the bronchial arteries is distributed throughout
can cause pulmonary infarction. the entire arterial bed of that lung, which allows to absorb this abrupt
Already in 1856 Virchow described necrosis of the lung in areas influx of bronchial blood. However, in distal PE, the pressure of bron
distal to pulmonary embolic obstruction. (9) Hampton and Castleman chial arterial inflow into the embolized area may be much greater than
demonstrated that (embolic) obstruction of a pulmonary artery may lead this small segment of the pulmonary arterial tree can accommodate
to a sequence that begins with hemorrhage into, and edema of, the (Fig. 1). At the same time, transient capillary ischemia (as the collateral
alveoli in areas distal to the obstruction. (10) In some cases this is circulation may not be immediately functional) leads to increased
reversible: the intra-alveolar blood is resorbed in 2–4 days, without vascular permeability. Endothelial cells are known to be very suscepti
necrosis or residual damage (intra-alveolar hemorrhage or ‘incomplete ble for hypoxia (15), however, as the alveoli remain ventilated in PE (i.e.
infarction’). If not absorbed, the extravasated erythrocytes may begin to continued oxygen availability), the endothelial barrier dysfunction may
break down into hemosiderin within 1–2 days, at which point actual be the result of an ischemia-induced inflammatory response. (16,17) The
necrosis of the surrounding lung parenchyma begins, and ‘true’ infarc increased blood flow together with the locally increased vascular
tion develops. The infarcted area is replaced by a fibrotic scar over a permeability causes extravasation of red blood cells into the alveoli. (11)
period of weeks (histologically) to months (radiologically) (Fig. 2). The resulting intra-alveolar hemorrhage resembles an infarct, but the
(10,11) tissue structures are preserved and the preexisting lung architecture may
As initial studies showed a higher occurrence of pulmonary infarc be restored after resorption of the blood. However, if the intra-alveolar
tion in patients with a compromised cardiac function, it was hypothe hemorrhage cannot be resorbed (due to inadequate blood flow), tissue
sized that chronic pulmonary venous hypertension and impaired infarction occurs, as was shown in animal models and autopsy studies.
forward flow through bronchial arteries are major contributing factors (9,10) Hence, although vascular obstruction usually leads to
Fig. 1. Central illustration
Central illustration regarding the pathophysiology, epidemiology, symptoms and prognosis of pulmonary infarction in acute pulmonary embolism.
163
Contents lists available at ScienceDirect
Thrombosis Research
journal homepage: www.elsevier.com/locate/thromres
Pulmonary infarction in acute pulmonary embolism
F.H.J. Kaptein a, L.J.M. Kroft b, G. Hammerschlag c, M.K. Ninaber d, M.P. Bauer e, M.
V. Huisman a, F.A. Klok a, *
a
Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands
b
Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands
c
Department of Respiratory and Sleep Medicine, The Royal Melbourne Hospital, Melbourne, Australia
d
Department of Pulmonology, Leiden University Medical Center, Leiden, the Netherlands
e
Department of Medicine – Acute Medicine, Leiden University Medical Center, Leiden, the Netherlands
A R T I C L E I N F O A B S T R A C T
Keywords: Pulmonary infarction results from occlusion of the distal pulmonary arteries leading to ischemia, hemorrhage
Pulmonary embolism and ultimately necrosis of the lung parenchyma. It is most commonly caused by acute pulmonary embolism (PE),
Pulmonary infarction with a reported incidence of around 30%. Following an occlusion of the pulmonary artery, the bronchial arteries
Hemorrhage
are recruited as primary source of perfusion of the pulmonary capillaries. The relatively higher blood pressure in
Diagnostic imaging
Prognosis
the bronchial circulation causes an increase in the capillary blood flow, leading to extravasation of erythrocytes
(i.e. alveolar hemorrhage). If this hemorrhage cannot be resorbed, it results in tissue necrosis and infarction.
Different definitions of pulmonary infarction are used in literature (clinical, radiological and histological),
although the diagnosis is nowadays mostly based on radiological characteristics. Notably, the infarcted area is
only replaced by a fibrotic scar over a period of months. Hence and formally, the diagnosis of pulmonary
infarction cannot be confirmed upon diagnosis of acute PE. Little is known of the impact and relevance of
pulmonary infarction in acute PE, and whether specific management strategies should be applied to prevent and/
or treat complications such as pain, pneumonia or post-PE syndrome. In this review we will summarize current
knowledge on the pathophysiology, epidemiology, diagnosis and prognosis of pulmonary infarction in the setting
of acute PE. We highlight the need for dedicated studies to overcome the current knowledge gaps.
1. Introduction if at all. Nevertheless, recognizing pulmonary infarction is clinically
relevant, both during the diagnostic phase as well as well as for making
Pulmonary infarction results from occlusion of the distal pulmonary management decisions. For instance, patients with pulmonary infarction
arteries leading to ischemia, hemorrhage and ultimately necrosis of the secondary to acute PE may be more likely to present with pleuritic chest
lung parenchyma. It is most often caused by acute pulmonary embolism pain and fever, and may more often require hospitalization and targeted
(PE), a frequently occurring and potentially life-threatening disease. (1) (intravenous) analgesic drugs to manage pain.
The reported annual incidence of PE varies between 75 and 269 cases In this review we will summarize current knowledge on the patho
per 100,000 persons, and mortality rates as high as 28% have been physiology, epidemiology, diagnosis and prognosis of pulmonary
described. (1–4) Although the dual blood supply to the lungs, i.e. the infarction in the setting of acute PE (Fig. 1).
pulmonary and the bronchial circulation, is thought to be protective
against pulmonary ischemia, pulmonary infarction can be found in 10 to 1.1. Pathophysiology
50% of all patients with PE. (5) This wide range is the result of the
difference in definition of pulmonary infarction used in literature, which The lungs receive deoxygenated blood from the pulmonary arteries
varies from pulmonary infarction as a clinical syndrome to a radiological (low pressure, high flow circulation) and oxygenated blood from the
finding or a histological phenomenon. Literature on this complication is bronchial arteries (at systemic pressure, i.e. 6 times that of the pulmo
limited, and pulmonary infarction is scarcely addressed in PE guidelines, nary arteries). The function of the pulmonary circulation is mainly gas
Abbreviations: PE, pulmonary embolism; CTPA, computed tomography pulmonary angiography.
* Corresponding author at: Department of Medicine – Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
E-mail address: (F.A. Klok).
https://doi.org/10.1016/j.thromres.2021.03.022
Received 27 January 2021; Received in revised form 5 March 2021; Accepted 24 March 2021
Available online 1 April 2021
0049-3848/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
, F.H.J. Kaptein et al. Thrombosis Research 202 (2021) 162–169
exchange, whereas the bronchial circulation supplies the bronchial to impaired resolution of alveolar hemorrhage and thus progression to
walls, the visceral pleura and the lung parenchyma with oxygenated local necrosis. (10–14)
blood (next to direct passive diffusion of oxygen in the latter). (6) This Dalen et al. showed that emboli in distal pulmonary branches were
dual blood supply has been thought to be protective against ischemic more likely to cause pulmonary infarction than more extensive and/or
injuries of the lungs. Animal models have shown that lung tissue may central obstructions. (11) Virchow described that after ligating a main
stay viable after ligation of the supplying pulmonary artery, where pulmonary artery, the collateral flow from the bronchial circulation
perfusion is maintained by the bronchial circulation: the bronchial ar enters the pulmonary circulation distal to the site of obstruction (as they
teries undergo smooth muscle wall hypertrophy and dilate to direct anastomose at the pre-pulmonary-capillary level), supporting Dalen’s
more oxygenated blood to ischemic lung tissue, and eventually increase observation. (9) In a central pulmonary artery occlusion, the high-
in number. (7,8) Even so, obstruction of a pulmonary artery by acute PE pressure inflow from the bronchial arteries is distributed throughout
can cause pulmonary infarction. the entire arterial bed of that lung, which allows to absorb this abrupt
Already in 1856 Virchow described necrosis of the lung in areas influx of bronchial blood. However, in distal PE, the pressure of bron
distal to pulmonary embolic obstruction. (9) Hampton and Castleman chial arterial inflow into the embolized area may be much greater than
demonstrated that (embolic) obstruction of a pulmonary artery may lead this small segment of the pulmonary arterial tree can accommodate
to a sequence that begins with hemorrhage into, and edema of, the (Fig. 1). At the same time, transient capillary ischemia (as the collateral
alveoli in areas distal to the obstruction. (10) In some cases this is circulation may not be immediately functional) leads to increased
reversible: the intra-alveolar blood is resorbed in 2–4 days, without vascular permeability. Endothelial cells are known to be very suscepti
necrosis or residual damage (intra-alveolar hemorrhage or ‘incomplete ble for hypoxia (15), however, as the alveoli remain ventilated in PE (i.e.
infarction’). If not absorbed, the extravasated erythrocytes may begin to continued oxygen availability), the endothelial barrier dysfunction may
break down into hemosiderin within 1–2 days, at which point actual be the result of an ischemia-induced inflammatory response. (16,17) The
necrosis of the surrounding lung parenchyma begins, and ‘true’ infarc increased blood flow together with the locally increased vascular
tion develops. The infarcted area is replaced by a fibrotic scar over a permeability causes extravasation of red blood cells into the alveoli. (11)
period of weeks (histologically) to months (radiologically) (Fig. 2). The resulting intra-alveolar hemorrhage resembles an infarct, but the
(10,11) tissue structures are preserved and the preexisting lung architecture may
As initial studies showed a higher occurrence of pulmonary infarc be restored after resorption of the blood. However, if the intra-alveolar
tion in patients with a compromised cardiac function, it was hypothe hemorrhage cannot be resorbed (due to inadequate blood flow), tissue
sized that chronic pulmonary venous hypertension and impaired infarction occurs, as was shown in animal models and autopsy studies.
forward flow through bronchial arteries are major contributing factors (9,10) Hence, although vascular obstruction usually leads to
Fig. 1. Central illustration
Central illustration regarding the pathophysiology, epidemiology, symptoms and prognosis of pulmonary infarction in acute pulmonary embolism.
163
