Apologise, but, dating pulmonary emboli that necessary
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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 was to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time.
Considering medico-legal cts it becomes fundamental to know if a pulmonary embolus is originated prior or subsequent to a traumatic event. In this study, we critically reviewed the histological section of thrombus from 30 fatal cases of PE as confirmed by post-mortem examination and final diagnosis.
The aim of this study was to evaluate the chronological transformation of the thrombus and to establish the time of death for these patients. Pulmonary vessels sections from 30 fatal cases of PE 25 cases of hospitalized patients and 5 cases of SUD defined according to commonly accepted criteria [ 14 ] were routinely collected and obtained from January to December at the University of Naples Federico II.
All the autopsies were performed according to the guidelines for autopsy from the Association for European Cardiovascular Pathology [ 10 ], and in all cases they were examined complete macroscopic autopsy with examination of the pulmonary arterial trunk by posterior approach.
A pulmonary embolism (PE) can strike with no symptoms. But most of the time, your body will let you know something's wrong. WebMD describes the telltale signs and explains when to call . Keywords: Pulmonary embolism, Thrombus dating, Sudden unexpected death, Forensic autopsy, Histology. Background. Venous thromboembolism (VTE) is a common cardiovascular disease Cited by: 2.
From the present study we excluded patients with diagnosis of systemic infection or underlying vasculitis. In addition, we performed an immunofluorescence method to identifying the deposition of factor VIII and fibrinogen. All stained samples were examined under digital and light microscope. The content of CD3 positive lymphocytes and collagen fibers was scored using a semi-quantitative three-point scale of range values.
For inflammatory cellular infiltration and fibrosis, we attributed score 0 for no increase, score 1, 2, or 3 for little, moderate, or high increase of cell content compared to adjacent tissue, respectively. The 30 autopsies included 19 male In 5 patients without clinical history of pre-existing pathologies the death occur in the first hour; thus they were considered cases of SUD.
In the other cases, 10 patients have cardiomyopathy under pharmacological treatment, 11 were patients hospitalized for abdominal or fracture surgery and 4 patients with cardiomyopathy received surgery after head injury. Regards the computed tomography exam, that were executed before the fatal death event, we reported a Mediastinal pulmonary artery n 7 To date, from computed tomography exam we reported a clot volume of The histological examination showed that 4 patients had a score 3 for cellular infiltrate and a score 2 for fibrosis platelet aggregation below the vascular endothelium with fibrin accumulation, small or absent erythrocyte infiltrate, absent or rare lympho-monocytic inflammatory elements.
The vessels of small and medium were 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 the first hour, we histologically observed the presence of platelet aggregation with few or no erythrocytes Fig.
The gray thrombus is made of platelets and fibrin, while red blood cells in the fibrin network characterize the red thrombus. Immunohistochemistry stain evidenced no presence of lymphocyte T cell infiltration within an hour Fig.
In the recent-medium thrombus, we observed the increased of the inflammatory cells Fig. Lysis of leukocytes involves the release of enzymes with subsequent digestion and destruction of erythrocytes and platelets with prevalent fibrin and cellular debris homogenization. The fibroblast cells and fibrosis were peripherally located in vascular tissuein the early hours and up to the third day Fig.
Finally, in the old thrombus, we have observed a proliferation of endothelial cells, increase of fibrosis and recanalization phenomena Fig.
Pulmonary Embolism : Symptoms
Thrombus formation in the first hour in SUD. Immunohistochemistry for anti-CD3 antibody at different times. Fibrosis score atdifferent times and revascularization. The major finding of this study was the determination of thrombus formation and its timely evolution in correlation to the death event.
In particular, we identified platelet activation through factor VIII and fibrinogen during the first hour. Secondly, we evaluated the inflammatory infiltrate and the evolution of the fibrotic state from 1th to 72th hour.
This provides a setting for malpractice claim. When in autopsy was observed vascular occlusion, it is essential to collect morphological macroscopic evaluation elements to distinguish a thrombus from an embolus or agonic coagulum. Macroscopically, it is important to note that the native thrombus adheres to the walls of the vessel in correspondence with an endothelial lesion, which is then examined by microscopy.
Moreover, the arterial thrombus is generally occluding, adheres to a parietal lesion in general atherosclerotic, is gray-white in color and friable and has the classic striped appearance [ 1 ].
On other hand, the venous thrombus is red and creates an endoluminal mold [ 1 ]. Instead, thrombus-embolus starts from a different vascular territory and is formed in the presence of an intact vessel.
Several studies have evaluated the discrepancies between clinical and autopsy diagnoses, demonstrating that the use of different imaging techniques seldom contribute directly to inaccurate or missed diagnoses [ 18 - 20 ]. Despite progress in imaging techniques and therapeutic treatment, the importance of autopsy remains crucial to elucidate the cause of death.
However, there are not forensic histological guidelines to determine the thrombus dating and its association to the death cause. This study introduces a methodological approach that combines clinical data derived from autopsy and histological analysis; so, it appears to be the first valid approach for the determination of thrombus formation through histological criteria.
A recent case report highlighted that although pathology skills are mandatory for an accurate chronological evaluation of fatal PE, histopathology and immunohistochemistry play both a crucial role in the evaluation of PE to the specific case [ 22 ]. Therefore, our experience in forensic thanatology [ 2324 ] reinforces the concept that microscopic observation is at the basis of a correct diagnosis and able to provide informations also for forensic practice and in the specific case in the age-old question of dating [ 13 ].
In cases of SUD, the estimate of small time intervals in thrombus formation is difficult but possible. Indeed, in the absence of anamnesis due to an arrhythmic events or other causes of cardiac death, they have been initially labeled as thrombus-embolic events. For the remaining cases, the classification in a time was fundamental to validate the diagnostic process and the treatment of patients with the aim of identifying a causal link that led to the death event.
Moreover, we can compare the formation of thrombus and its resolution to wound healing. In both of these processes, in fact, the inflammatory elements, the bioactive molecules, such as cytokines and growth factors, and the remodeling of the matrix play an important role [ 25 - 27 ].
Indeed, all these multiple cellular and extracellular pathways favor a pro-thrombotic status, that might be reversed by opposite anti-thrombotic mechanisms causing thrombus resolution [ 1 ].
On the other hand, the loss of these anti-thrombotic protective mechanisms might consequently evolve towards worse prognosis and SUD events in patients with PE [ 3 - 8 ]. To date, thrombi causing pulmonary embolism are rich in fibrin and trapped red blood cells, and are referred to as red clots [ 28 ]. In this setting, the coagulation cascade represented by three pathways as the extrinsic pathway tissue factor and factor VIIa, which is the primary activator of the cascadethe intrinsic pathway factor XIIa, factor XIa, factor IXa and factor VIIIa, which amplifies the cascadeand the common pathway factor Xa, factor Va and thrombin, which generates thrombin and fibrinplays a relevant role in thrombotic processes [ 30 ].
However, we might speculate that, in the early phase of thrombus formation a specific anti-thrombotic therapy might inhibit a specific target pathway of the coagulation cascade [ 31 ].
This therapeutic effect might consequently impact on ongoing thrombotic process [ 31 ], and this might consequently ameliorate clinical outcomes in patients with EP. We are aware that this retrospective study has major limitations represented by the small number of autopsies included and the inter-operator sampling variability but our considerations may be useful for successive studies aimed to evaluated the dating of thrombus formation.
Moreover, the acquired and inherited thrombophilic risk factors for PE is not considered. In the present research we have identified by histological analysis a timing in the physiopathology of the thrombus early, recent, recent-medium, medium, old.
Since often the antigenicity of tissues and cells is lost with post-mortal phenomena, the risk of detect false positives or negatives to immunohistochemistry analysis might increase. Therefore, we believe that the traditional histology after a macroscopic observation and after a good sampling is important to identify the time of thrombus formation. The immunohistochemically and immunofluorescence methods might only confirm what morphologically the pathologist observes.
In the present study we identified by histological analysis a timing in the physiopathology of the thrombus formation as early, recent, recent-medium, medium, and old, allowing to determine the exact time of death. However, during the 1th hour of thrombosis we reported a first thrombotic process caused by platelet activation through factor VIII and fibrinogen.
Consequently, a second phase and timing of thrombosis is caused by the inflammatory infiltrate and the evolution of the fibrotic state from 1th to 72th hour. In our opinion, a deeper knowledge of the different phases of thrombus formation and of its link with time of death might open new investigations to develop new biomarkers for the early identification and the monitoring of patients with EP and higher risk of death.
Conversely, the identification of different timing and pathological processes during thrombosis and EP events might open a new scenario regards the opportunity to practice a prophylactic anticoagulation, according to risk factors, in patients with thrombi formed prior or following a traumatic event.
Therefore, we might speculate that the time to thrombus formation and death might change the current clinical practice. The autopsy and diagnosis of pulmonary thrombo-embolism. Forensic Sci Med Pathol. Steiner I.
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Histological criteria for age determination of fatal venous thromboembolism. Int J Legal Med. Literature review and our experience in forensic thanatology.
Pulmonary eosinophilic inflammatory infiltration post-intensive care in a nearly drowned young man with papillary fibroelastoma: a rare complication discovered by forensic autopsy.
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Definition - Pulmonary embolus (PE) refers to obstruction of the pulmonary artery or one of its branches by material (eg, thrombus, tumor, air, or fat) that originated elsewhere in the body. This topic review focuses upon PE due to thrombus. Tumor, air, and fat emboli . Thrombosis of pulmonary arteries, are rare and occurs only in pulmonary hypertension and pulmonary atherosclerosis. More than 95 of pulmonary emboli arise in deep veins of legs. Nov 08, The aim of our study was to verify the morphological and histological criteria of fatal cases of PE and evaluate the dating of thrombus formation considering 5 ranges of time. Cited by: 2.
Correspondence to Celestino Sardu. Written consent was obtained from the next-of-kin of the patients studied, to authorize the analysis of tissue samples in further research.
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Reprints and Permissions. Mansueto, G. The dating of thrombus organization in cases of pulmonary embolism: an autopsy study. BMC Cardiovasc Disord 19, Download citation. Received : 21 March Accepted : 04 October Published : 08 November Skip to main content Advertisement. Search all BMC articles Search. Download. Abstract Background Pulmonary embolism PE is associated to high mortality rate worldwide.
Methods Pulmonary vessels sections were collected from January to December Results The 30 autopsies included 19 males Conclusions After a macroscopic observation and a good sampling traditional histology, it is important to identify the time of thrombus formation.
Clinical trial number NCT Trial registration The trial registry is Cliniclatrials.
The dating of thrombus organization in cases of pulmonary embolism: an autopsy study
Background Venous thromboembolism VTE is a common cardiovascular disease with high mortality rate worldwide [ 1 ]. Methods Patients and samples Pulmonary vessels sections from 30 fatal cases of PE 25 cases of hospitalized patients and 5 cases of SUD defined according to commonly accepted criteria [ 14 ] were routinely collected and obtained from January to December at the University of Naples Federico II.
Table 1 Clinical and demographic characteristics of pulmonary embolism cases Full size table. Table 2 Histological score of inflammatory infiltrate and fibrosis Full size table. Results The 30 autopsies included 19 male Table 3 Score related to dating thrombus formation Full size table. Table 4 Score of histological observation with optical microscopy Full size table. Full size image.
Discussion The major finding of this study was the determination of thrombus formation and its timely evolution in correlation to the death event. Conclusions In the present study we identified by histological analysis a timing in the physiopathology of the thrombus formation as early, recent, recent-medium, medium, and old, allowing to determine the exact time of death.
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Dating pulmonary emboli
Article Google Scholar 6. Article Google Scholar 9. Article Google Scholar Google Scholar The effects of embolism on gas exchange are :. The ventilation of ushawchapman.comefused lung adds to the work of breathing and produces tachypnea and a sense of dyspnea.
Transient constriction of smooth muscle in airways and alveolar ducts occurs in response to vagal reflexes and humoral mediators such as serotonin, adenosine diphosphateand thromboxane released from platelets.
Some patients manifest asthma-like wheezing. Impaired surfactant production is a delayed effect that produces edema and atelectasis. They include a rise in pulmonary artery pressure and in severe cases congestive heart failure and shock. Massive pulmonary embolism is a well-recognized cause of sudden death, which may be virtually instantaneous or extend over a period of a few minutes. The major pulmonary arteries are distended with clots that are often coiled or twisted and bear the imprint of venous valves.
The lung parenchyma shows little change except congestion, which presumably comes by way of the bronchial circulation.
Sublethal thromboemboli are often recurrent. Consequently, it is common to find emboli of varied age at autopsy. Fresh emboli are poorly adherent to the vessel wall but can be distinguished from postmortem clots because they distend the artery, have a drier, more granular surface, and seem less elastic.
Lines of Zahn and imprints of valves are diagnostic. Older thrombi are adherent and retracted to varying degrees. The fate of nonfatal emboli is variable. Fibrinolytic mechanisms produce dissolution of the embolus within a few days, as demonstrated by serial angiograms and lung scans.
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