Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc
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Review

Volume 17, Number 1, January 2025, pages 1-13

Strategies in Management of Pulmonary Embolism With Acute Ischemic Stroke: A Systematic Review

Figure

↓  Figure 1. Article selection flow sheet per PRISMA 2020 guidelines [7].
Figure 1.

Tables

↓  Table 1. Risk of Bias
 
Questions Dada et al, 2018 [28] Barros-Gomes et al, 2018 [24] Delgado et al, 2012 [10] Hattori et al, 2019 [29] Christiansen et al, 2017 [17] De Oliveira et al, 2016 [27] Gunta and Kamath, 2012 [11] Konala et al, 2019 [18] Lio et al, 2019 [13] Bagate et al, 2018 [12] Pan et al, 2019 [20] Pelletier et al, 2010 [9] Saleh Velez and Ortiz Garcia, 2021 [19] Duy et al, 2019 [25] Ozsancak Ugurlu et al, 2015 [23] Xie et al, 2014 [16] Chakir et al, 2021 [21] Naidoo and Hift, 2011 [15] Nam et al, 2015 [26] Omar et al, 2013 [22] Jayalakshmi et al, 2021 [14]
Selection
1. Does the patient(s) represent(s) the whole experience of the investigator (center) or is the selection method unclear to the extent that other patients with similar presentation may not have been reported?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Ascertainment
2. Was the exposure adequately ascertained?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Ascertainment
3. Was the outcome adequately ascertained?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Causality
4. Were other alternative causes that may explain the observation ruled out?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Causality
5. Was there a challenge/rechallenge phenomenon?		 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
Causality
6. Was there a dose response effect?		 N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
Causality
7. Was follow-up long enough for outcomes to occur?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Reporting
8. Is the case(s) described with sufficient details to allow other investigators to replicate the research or to allow practitioners make inferences related to their own practice?		 Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes

 

↓  Table 2. GRADE Analysis for Included Studies
 
Study Year Study design Risk of bias Inconsistency Indirectness Imprecision Publication bias Quality of evidence GRADE
Dada et al [28] 2018 Case report High None Direct None Not significant Low Low
Barros-Gomes et al [24] 2018 Case report High None Direct None Not significant Low Low
Delgado et al [10] 2012 Case report High None Direct None Not significant Low Low
Hattori et al [29] 2019 Case report High None Direct None Not significant Low Low
Christiansen et al [17] 2017 Case report High None Direct None Not significant Low Low
De Oliveira et al [27] 2016 Case report High None Direct None Not significant Low Low
Gunta and Kamath [11] 2012 Case report High None Direct None Not significant Low Low
Konala et al [18] 2019 Case report High None Direct None Not significant Low Low
Lio et al [13] 2019 Case report High None Direct None Not significant Low Low
Bagate et al [12] 2018 Case report High None Direct None Not significant Low Low
Pan et al [20] 2019 Case report High None Direct None Not significant Low Low
Pelletier et al [9] 2010 Case report High None Direct None Not significant Low Low
Saleh Velez and Ortiz Garcia [19] 2021 Case report High None Direct None Not significant Low Low
Duy et al [25] 2019 Case report High None Direct None Not significant Low Low
Ozsancak Ugurlu et al [23] 2015 Case report High None Direct None Not significant Low Low
Xie et al [16] 2014 Case report High None Direct None Not significant Low Low
Chakir et al [21] 2021 Case report High None Direct None Not significant Low Low
Naidoo et al [15] 2011 Case report High None Direct None Not significant Low Low
Nam et al [26] 2015 Case report High None Direct None Not significant Low Low
Omar et al [22] 2013 Case report High None Direct None Not significant Low Low
Jayalakshmi et al [14] 2021 Case report High None Direct None Not significant Low Low

 

↓  Table 3. Patient Information, Risk Factors and Presenting Symptoms
 
Study Age/sex Risk factors Presenting symptoms
COPD: chronic obstructive pulmonary disease; DVT: deep vein thrombosis; GI: gastrointestinal; HIV: human immunodeficiency virus; OCP: oral contraceptive pill; PE: pulmonary embolism; SLE: systemic lupus erythematosus.
Pelletier et al, 2010 [9] 35/F Recent leg varicosal stripping, one spontaneous abortion, OCP use Collapsed, altered consciousness, expressive aphasia, subtle facial asymmetry
Delgado et al, 2012 [10] 76/F Hypertension, dyslipidemia Sudden right leg paresis and hypoesthesia
Gunta and Kamath, 2012 [11] 16/F Long car ride, OCP, family history of venous thromboses and PE, MTHFR mutation, antithrombin III deficiency Unresponsive, labored respirations, shortness of breath, cough, leg pain for 2 days
Bagate et al, 2018 [12] 44/M Psychiatric disorder Non-shockable cardiac arrest, impaired consciousness
Lio et al, 2019 [13] 69/M Testicular carcinoma Signs of cardiogenic shock, questionable GI bleeding
Jayalakshmi et al, 2021 [14] 52/M Not mentioned Not mentioned
Naidoo and Hift, 2011 [15] 38/F Immobility, dilated cardiomyopathy, HIV on antiretroviral therapy Dyspnea, pleuritic chest pain, right-sided hemiplegia
Xie et al, 2014 [16] 55/F History of varicose veins of lower extremities Chest distress, dyspnea, loss of consciousness, sudden non-fluent language, dyskinesis of right extremities
Christiansen et al, 2017 [17] 59/F Post-operative day 2 abdominoplasty and liposuction, OCP Left-sided weakness, dysarthria, acute respiratory distress
Konala et al, 2019 [18] 82/M Type 2 diabetes mellitus, previous lower extremity DVT Loss of consciousness while urinating, mild dyspnea before syncope
Saleh Velez and Ortiz Garcia, 2021 [19] 72/F Not mentioned Collapsed, comatose state, flaccid quadriplegia, cardiac arrest
Saleh Velez and Ortiz Garcia, 2021 [19] 75/F Hypertension Mild dysarthria, right arm paresis, severe pleuritic pain, shortness of breath
Pan et al, 2019 [20] 27/F Post-operative day 7 C-section, Glenn anastomosis 7 years prior for cor biloculare Dizziness, chest tightness, dysarthria, facial asymmetry, right hemiparesis
Chakir et al, 2021 [21] 60/M Type II diabetes, COVID-19 infection Left hemiplegia, typical anginal chest pain, hypotonia, left sensory deficit
Omar et al, 2013 [22] 69/M Post-operative day 1 right total hip replacement, hypertension, dyslipidemia, prior surgical repair of iliac artery aneurysm Shortness of breath, wheezing, confusion, aphasia, right-sided weakness
Ozsancak Ugurlu et al, 2015 [23] 64/F Not mentioned Shortness of breath, chest pain, recurrent syncope, convulsion
Barros-Gomes et al, 2018 [24] 68/F Hypertension, tobacco abuse, COPD Facial droop, right arm weakness, aphasia
Duy et al, 2019 [25] 53/F Three prior ischemic strokes Unconsciousness, dyspnea, right hemiplegia
Nam et al, 2015 [26] 69/F Not significant Dyspnea, drowsy mental status, right-sided hemiplegia after surgery
De Oliveira et al, 2016 [27] 41/F Post-operative day 10 lap cholecystectomy Dysarthria, acute respiratory distress, left calf tenderness
Dada et al, 2018 [28] 55/M Not mentioned Left facial droop, left-sided weakness, garbled speech
Hattori et al, 2020 [29] 68/F History of multiple cerebral emboli, SLE on prednisolone Dysarthria, dysphagia, left facial paralysis

 

↓  Table 4. Descriptive Analysis of the Extracted Data From Included Studies
 
SD: standard deviation.
Patients, N 22
Case reports, N 20
Case series, N 1
Female, N (%) 15 (68.18%)
Male, N (%) 7 (31.82%)
Mean patient age, years 56.68 (SD: 16.8)
Median patient age, years 59.5

 

↓  Table 5. Prevalence of Main Predisposing Factors
 
Predisposing factors N %
ART: antiretroviral therapy; AT: antithrombin; COPD: chronic obstructive pulmonary disease; DVT: deep vein thrombosis; HIV: human immunodeficiency virus; OCP: oral contraceptive pill; PE: pulmonary embolism; SLE: systemic lupus erythematosus.
PE
  OCP use 4 18.18
  Post major surgical interventions 4 18.18
  Immobility 2 9.09
  Varicose veins 2 9.09
  Prior lower extremity DVT 1 4.55
  Family history of venous thromboses and PE 1 4.55
  Homozygous for MTHFR mutation/ATIII deficiency 1 4.55
  Tobacco abuse 1 4.55
  COPD 1 4.55
  HIV on ART 1 4.55
  SLE 1 4.55
  Pregnancy, especially first 6 weeks postpartum 1 4.55
  Compression by mass (testicular carcinoma) 1 4.55
  History of Glenn anastomosis 1 4.55
  COVID-19 infection 1 4.55
Ischemic stroke
  Hypertension 5 22.73
  Dyslipidemia 3 13.64
  Type 2 diabetes mellitus 2 9.09
  Prior thromboembolic strokes 2 9.09
  Tobacco abuse 1 4.55

 

↓  Table 6. Case Reports Describing Multiple Permutations of Treatment Combinations and Their Outcomes
 
Study Location of PE Treatment of PE Location of stroke Treatment of stroke PFO and treatment DVT PFO with thrombus Outcome
ACA: anterior cerebral artery; DVT: deep vein thrombosis; LMWH: low molecular weight heparin; ICA: internal carotid artery; IV: intravenous; IVC: inferior vena cava; MCA: middle cerebral artery; MT: mechanical thrombectomy; PE: pulmonary embolism; PFO: patent foramen ovale; rt-PA: recombinant tissue plasminogen activator.
Pelletier et al, 2010 [9] Bilateral Heparin infusion Left tempoparietal rt-PA, IVC filter Present, closed Negative Marked improvement
Naidoo and Hift, 2011 [15] Bilateral Streptokinase Left frontoparietal Not treated, since neuro improved Absent Positive, right Marked improvement
Delgado et al, 2012 [10] Bilateral segmental, subsegmental Heparin infusion Left ACA rt-PA Present, not closed Not mentioned Marked improvement
Gunta and Kamath, 2012 [11] Bilateral main Heparin infusion, LMWH IVC filter Left striatocapsular and internal capsule MT followed by aspirin Present, planned closure at later date positive Marked improvement
Omar et al, 2013 [22] Descending trunk, right main segmental/subsegmental IVC filter Left MCA MT Present, not a candidate for PFO closure Not mentioned Bed-ridden and non-verbal
Ozsancak Ugurlu et al, 2015 [23] Bilateral main into lobar branches Percutaneous embolectomy (MT), heparin infusion Left occipital and bilateral cerebellar lobes Not treated Not mentioned Not mentioned Marked improvement
Xie et al, 2014 [16] Bilateral Urokinase, LMWH, aspirin and clopidogrel Left temporal, parietal, insular lobes and basal ganglia Increased aspirin and clopidogrel dose Absent Negative Marked improvement, recurrence of PE 10 months later
Nam et al, 2015 [26] Bilateral Surgical embolectomy Left MCA and multifocal, embolic infarctions in right cerebrum Decompressive craniectomy Present, closed Not mentioned Biatrial thrombus across PFO Long-term ventilatory support, no neuro improvement
De Oliveira et al, 2016 [27] Not mentioned Surgical thrombectomy Not mentioned Not mentioned Present, closed Present, left Right atrial thrombus straddling PFO Marked improvement
Christiansen et al, 2017 [17] Bilateral lobar and segmental rt-PA, LMWH, aspirin Right MCA rt-PA, MT Present, not closed Negative Abdominal hematoma post thrombolysis, marked improvement
Barros-Gomes et al, 2018 [24] Bilateral MT Left ICA Not treated Present, not closed Not mentioned Thrombus in PFO Not reported
Bagate et al, 2018 [12] Bilateral Heparin infusion Left parietal lobe Not treated Present, not closed Not mentioned Brain death
Dada et al, 2018 [28] Main Surgical clot removal, heparin infusion Left temporal occipital lobe rt-PA not given, outside window Present, closed Positive, right Biatrial thrombus straddling PFO Marked improvement
Duy et al, 2019 [25] Bilateral Percutaneous thrombectomy (MT), heparin infusion Left MCA MT Present, anticoagulant therapy only Negative Marked improvement
Konala et al, 2019 [18] Bilateral main rt-PA, heparin infusion, IVC filter Left caudate/putamen area Not treated Present, patient refused closure Positive, bilateral Biatrial thrombus straddling PFO Marked improvement
Hattori et al, 2020 [29] Bilateral main Surg pulmonary embolectomy, IVC filter Brain stem and left occipital lobe Not treated Present, closed Positive Thrombus straddling PFO Marked improvement
Lio et al, 2019 [13] Bilateral lobar Heparin infusion Basilar artery occlusion MT Present, not closed Not mentioned Dead
Pan et al, 2019 [20] Left inferior and right lobar LMWH Left basal ganglia Not treated Absent Negative Marked improvement
Saleh Velez and Ortiz Garcia, 2021 [19] Bilateral Medical therapy Right ICA Medical therapy Present Negative Dead
Saleh Velez and Ortiz Garcia, 2021 [19] Bilateral main Catheter-directed thrombolysis, IV heparin Left MCA rt-PA deferred, unknown, last time well Present Positive, left Marked improvement
Jayalakshmi et al, 2021 [14] Not mentioned Heparin Right MCA Decompressive craniotomy Not mentioned Not mentioned Marked improvement
Chakir et al, 2021 [21] Bilateral LMWH Right MCA Aspirin Absent Negative Slight improvement in neuro

 

↓  Table 7. Frequencies of Treatment Approaches for PE
 
Treatment approach for PE Number of cases
AC: anticoagulation; LMWH: low molecular weight heparin; IVC: inferior vena cava; MT: mechanical thrombectomy; PE: pulmonary embolism; rt-PA: recombinant tissue plasminogen activator.
Thrombolysis 5
  rt-PA + AC 2
  Streptokinase alone 1
  Urokinase + AC 1
  Catheter thrombolysis + AC 1
Heparin 6
  Post rt-PA 2
  Post MT 2
  With craniotomy 1
  Only 1
LMWH 2
  Only 1
  Aspirin 1
IVC filter only 1
Medical therapy only 1
Catheter-directed thrombectomy 3
  MT 1
  Percutaneous thrombectomy + heparin 2
Surgical approach 4
  Surgical embolectomy/thrombectomy 2
  Surgical pulmonary embolectomy + IVC 1
  Surgical clot removal + heparin 1

 

↓  Table 8. Prevalence of PFO, PFO With Thrombus, and DVT in Patients With Concurrent PE and AIS
 
Findings Present Absent Not mentioned
AIS: acute ischemic stroke; DVT: deep vein thrombosis; PE: pulmonary embolism; PFO: patent foramen ovale.
PFO 16 (72.72%) 4 (18.18%) 2
PFO with thrombus 6/16 (37.5%)
DVT 7 (31.81%) 7 (31.81%) 8

 

↓  Table 9. Outcomes by Treatment Modality in Patients With PE and AIS
 
Treatment modality Symptom improvement and survival Deterioration in functional status Mortality Not reported Total cases
AIS: acute ischemic stroke; PE: pulmonary embolism.
Anticoagulation 5 (62.5%) 2 25.0%) 1 (12.5%) 0 (0.0%) 8
Thrombolysis 5 (100.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) 5
Catheter-directed thrombectomy 2 (66.7%) 0 (0.0%) 0 (0.0%) 1 (33.3%) 3
Surgical thrombectomy 3 (75.0%) 1 (25.0%) 0 (0.0%) 0 (0.0%) 4
Treatment without anticoagulation or thrombolytic therapy 0 (0.0%) 1 (50.0%) 1 (50.0%) 0 (0.0%) 2
Total 15 (68.2%) 4 (18.2%) 2 (9.1%) 1 (4.5%) 22