Sex-specific differences in pulmonary embolism

Keller, Karsten; Rappold, L.; Gerhold‐Ay, Aslihan; Hobohm, Lukas; Hasenfuß, Gerd; Konstantinides, Stavros; Dellas, Claudia; Lankeit, Mareike

doi:10.1016/j.thromres.2019.04.020

Cited by 25 publications

(53 citation statements)

References 47 publications

(76 reference statements)

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“…Both K s and CLT were associated with positive TnT and NT-proBNP, biomarkers related to the cardiac injury, cardiac stress, and RV dysfunction in acute PE 3 , 22 . Levels of NT-proBNP have been shown to predict the 30-day adverse outcome in acute PE patients 23 . Of note, the 2019 ESC Guidelines for the diagnosis and management of acute PE downplayed the role of NT-proBNP in PE mortality risk estimation 3 , however, it is still considered as an additional prognostic biomarker.…”

Section: Discussionmentioning

confidence: 99%

Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk

Ząbczyk

Natorska

Janion−Sadowska

et al. 2020

Sci Rep

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Venous thromboembolism is associated with formation of denser fibrin clots resistant to lysis. We investigated whether prothrombotic plasma clot properties are associated with the severity of acute pulmonary embolism (PE). We enrolled 126 normotensive acute PE patients (aged 58 ± 14 years) and 25 age- and sex-matched healthy controls. Plasma fibrin clot permeability (K s ), clot lysis time (CLT), endogenous thrombin potential (ETP), plasminogen activator inhibitor-1 (PAI-1), and citrullinated histone H3 (citH3) were evaluated on admission. PE patients compared to controls had 370% higher citH3 levels, 41% higher ETP, 16.5% reduced K s , and 25.6% prolonged CLT. Patients with intermediate-high (n = 29) and intermediate-low (n = 77) PE mortality risk had reduced K s and prolonged CLT, increased PAI-1 and ETP as compared to low-risk PE (n = 20) patients. Prolonged CLT was predicted by PAI-1 and citH3, while low K s by C-reactive protein. During a 12-month follow-up 9 (7.1%) patients who had 24% higher ETP, 45% higher citH3 levels, and 18% prolonged CLT at baseline died. High ETP combined with elevated citH3 levels and prolonged CLT was associated with eightfold increased risk of PE-related death. Prothrombotic fibrin clot properties and enhanced neutrophil extracellular traps formation are associated with higher early mortality risk in acute PE patients, which suggests a prognostic role of these biomarkers.

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Section: Discussionmentioning

confidence: 99%

Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk

Ząbczyk

Natorska

Janion−Sadowska

et al. 2020

Sci Rep

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“…94,95 Although sex is not a factor in the sPESI, several studies have suggested that it may predict adverse outcomes more accurately in women than men despite that it performs well in both sexes. 57,96 In addition, using sex-specific biomarker cutoff values was shown to improve the performance and predictive value of the 2014 ESC guidelines, though this finding has not been replicated. 57 Future investigations should focus on sex-specific prognostic factors in acute PE.…”

Section: Severity Assessment and Treatmentmentioning

confidence: 96%

“…however, tachycardia and hypoxia reliably predict adverse outcomes in both sexes. 57 Although sex was included in the 2005 PESI score, in the derivation of the simplified PESI score in 2010, it was not found to be a significant predictor of mortality. 91,94 The sPESI score has since been both internally and externally validated in cohorts that were pre-dominantly female (55%-60%).…”

Section: Severity Assessment and Treatmentmentioning

confidence: 98%

“…56 Hemoptysis is relatively uncommon as a presenting complaint (2%-7% of patients) but is slightly more common in men. 42,57 Calf pain also may be more predictive of PE in men than in women. 53 The diagnostic approach to patients with suspected PE begins with assessment of pretest probability using clinical judgment and structured clinical decision tools.…”

Section: Clinical Evaluation and Diagnosismentioning

confidence: 99%

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Crucial considerations: Sex differences in the epidemiology, diagnosis, treatment, and outcomes of acute pulmonary embolism in non‐pregnant adult patients

et al. 2021

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Acute pulmonary embolism (PE) affects over 600,000 Americans per year and is a common diagnostic consideration among emergency department patients. Although there are well-documented differences in the diagnosis, treatment, and outcomes of cardiovascular conditions, such as ischemic heart disease and stroke, the influence of sex and gender on PE remains poorly understood. The overall age-adjusted incidence of PE is similar in women and men, but women have higher relative rates of PE during early and mid-adulthood (ages 20-40 years); whereas, men have higher rates of PE after age 60 years. Women are tested for PE at far higher rates than men, yet women who undergo computed tomography pulmonary angiography are ultimately diagnosed with PE 35%-55% less often than men. Among those diagnosed with PE, women are more likely to have severe clinical features, such as hypotension and signs of right ventricular dysfunction. When controlled for PE severity, women are less likely to receive reperfusion therapies, such as thrombolysis. Finally, women have more bleeding complications for all types of anticoagulation. Further investigation of possible sex-specific diagnostic and treatment algorithms is necessary in order to more accurately detect and treat acute PE in non-pregnant adults.

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“…Although increased incidence of pulmonary embolism in women among both of these age groups may be contributing to this, whether true sex and/or gender differences exist in case fatality rates remains to determined. Data from registry studies have suggested a higher in-hospital and 30 day pulmonary embolism related mortality in women,21 whereas other studies have not observed a difference 22. Subgroup analyses of RCTs comparing warfarin and DOAC therapy have not suggested a difference.…”

Section: Epidemiologymentioning

confidence: 98%

Pulmonary embolism: update on management and controversies

Duffett

Castellucci

Forgie

2020

BMJ

141

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Pulmonary embolism is a common and potentially fatal cardiovascular disorder that must be promptly diagnosed and treated. The diagnosis, risk assessment, and management of pulmonary embolism have evolved with a better understanding of efficient use of diagnostic and therapeutic options. The use of either clinical probability adjusted or age adjusted D-dimer interpretation has led to a reduction in diagnostic imaging to exclude pulmonary embolism. Direct oral anticoagulation therapies are safe, effective, and convenient treatments for most patients with acute venous thromboembolism, with a lower risk of bleeding than vitamin K antagonists. These oral therapeutic options have opened up opportunities for safe outpatient management of pulmonary embolism in selected patients. Recent clinical trials exploring the use of systemic thrombolysis in intermediate to high risk pulmonary embolism suggest that this therapy should be reserved for patients with evidence of hemodynamic compromise. The role of low dose systemic or catheter directed thrombolysis in other patient subgroups is uncertain. After a diagnosis of pulmonary embolism, all patients should be assessed for risk of recurrent venous thromboembolism to guide duration of anticoagulation. Patients with a venous thromboembolism associated with a strong, transient, provoking risk factor can safely discontinue anticoagulation after three months of treatment. Patients with an ongoing strong risk factor, such as cancer, or unprovoked events are at increased risk of recurrent events and should be considered for extended treatment. The use of a risk prediction score can help to identify patients with unprovoked venous thromboembolism who can benefit from extended duration therapy. Despite major advances in the management of pulmonary embolism, up to half of patients report chronic functional limitations. Such patients should be screened for chronic thromboembolic pulmonary hypertension, but only a small proportion will have this as the explanation of their symptoms. In the remaining patients, future studies are needed to understand the pathophysiology and explore interventions to improve quality of life.

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Sex-specific differences in pulmonary embolism

Cited by 25 publications

References 47 publications

Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk

Prothrombotic fibrin clot properties associated with NETs formation characterize acute pulmonary embolism patients with higher mortality risk

Crucial considerations: Sex differences in the epidemiology, diagnosis, treatment, and outcomes of acute pulmonary embolism in non‐pregnant adult patients

Pulmonary embolism: update on management and controversies

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