Pulmonary Embolism: an Autopsy Study

NCT ID: NCT03887819

Last Updated: 2019-03-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 15 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2015-01-01
• Study Completion Date: 2019-01-01

Brief Summary

BACKGROUND: Pulmonary embolism (PE) is associated to high mortality rate worldwide. However, the diagnosis of PE often results inaccurate. Many cases of PE are incorrectly diagnosed or missed and they are often associated to sudden unexpected death (SUD). In forensic practice, it is important to establish the time of thrombus formation in order to determine the precise moment of death. The autopsy remains the gold standard method for the identification of death cause allowing the determination of discrepancies between clinical and autopsy diagnoses. The aim of our study will be to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time.

METHODS: Pulmonary vessels sections will be collected from January 2010 to December 2017. Sections of thrombus sampling will be stained with hematoxylin and eosin. The content of infiltrated cells, fibroblasts and collagen fibers will be scored using a semi-quantitative three-point scale of range values.

Hypothesis: After a macroscopic observation and a good sampling traditional histology, it will be important to identify the time of thrombus formation. We will identify histologically a range of time in the physiopathology of the thrombus (early, recent, recent-medium, medium, old), allowing to determine the dating of thrombus formation and the exact time of death.

Detailed Description

Introduction Venous thromboembolism (VTE) is pathological condition caused by deep vein thrombosis (DVT) with a consequent detaching of thrombus from original sites , that by embolic phenomena and traveling to the lung might result in pulmonary embolism (PE). As first, the diagnosis of PE might result frequently inaccurate, with many cases incorrectly diagnosed or missed. Secondly, it might be caused by several conditions such as surgery and trauma, with a consequent relevant clinical impact and worse prognosis. However, clinical presentation of PE range from those completely asymptomatic or with an insidious disease, to sudden unexpected death (SUD. SUD may be defined as a natural and fatal event that occurs within 1 h of the beginning of symptoms in an apparently healthy subject or in those with a disease not particularly severe to cause an abrupt outcome. Since the diagnosis is challenging, epidemiological data regarding PE mortality remain limited.To date, it is estimated that PE is responsible for 100,000 annual deaths only in the United States and approximately 25-30% of patients had SUD as consequence of PE.

However, in our opinion it might be essential to collect morphological macroscopic evaluation elements to distinguish a thrombus from an embolus or agonic coagulum.To date, the autopsy may be useful for the determination of the identification of death cause, and to establish the dating of transformation of thrombus and evaluate any professional error. Therefore, in this study, authors will critically review the histological section of thrombus from 30 fatal cases of PE pulmonary embolus by autopsies, and its correlation and origin prior or subsequent to a traumatic event, as confirmed by post-mortem examination and final diagnosis. Moreover, the aim of this study will be to evaluate the chronological transformation of the thrombus and to establish the time of death for each subject.

Materials and methods Patients and samples Pulmonary vessels sections will be collected from 30 fatal cases of PE (25 cases of hospitalized patients and 5 cases of SUD) defined according to commonly accepted criteria were routinely collected from January 2010 to December 2017 at the University of Naples Federico II.

Histological evaluation According to the guidelines for autopsy from the Association for European Cardiovascular Pathology, and in all cases authors will examine the pulmonary arterial trunk by posterior approach. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H&E) for diagnosis. The original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate. In addition, authors will be performed an immunofluorescence method to identifying the deposition of factor VIII and fibrinogen. A Picro Sirius Red/Fast Green will be used for differential staining of collagen during matrix production phase. All stained samples will be examined under infiltrate, absent or rare lympho-monocytic inflammatory elements. The vessels of small and medium will be involved, mainly from the main branches of the pulmonary vessels.In2 patients we observed a score 3 for cellular infiltrate and 1 for fibrosis. In 10 cases (5 heart patients, 2 cardiac patients undergoing surgery and 3 surgeries), authors will observe an increase (score 2) in the digital and light microscope.

Conditions

Pulmonary Embolism

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

Hystological evaluation

The original tissues samples will be fixed in 10% neutral buffered formalin and embedded in paraffin blocks. Sections (4 μm thick) will be stained with hematoxylin and eosin stain (H\&E) for diagnosis. The immunohistochemistry for anti-LCA, anti-CD68, and anti-CD3 will be performed to identify the inflammatory infiltrate.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• diagnosis of acute pulmonary embolism;
• patients died after the pulmonary embolic event.

Exclusion Criteria

• diagnosis of non acute pulmonary embolism;
• patients survived after the pulmonary embolic event.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Campania Luigi Vanvitelli

OTHER

Sponsor Role: lead

Responsible Party

Celestino Sardu

clinical professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

References

Mansueto G, Costa D, Capasso E, Varavallo F, Brunitto G, Caserta R, Esposito S, Niola M, Sardu C, Marfella R, Napoli C, Paternoster M. The dating of thrombus organization in cases of pulmonary embolism: an autopsy study. BMC Cardiovasc Disord. 2019 Nov 8;19(1):250. doi: 10.1186/s12872-019-1219-8.

Reference Type: DERIVED

PMID: 31703628 (View on PubMed)

Other Identifiers

SecondUNI 21.03.2019

Identifier Type: -

Identifier Source: org_study_id