A study of clinicopathological characteristics, symptoms and patients experiences related to outcomes in people with cancer and I-PE

Background: The clinical course of incidental pulmonary embolism in cancer population represents an area of controversy. It presents a growing challenge for clinicians because of a lack of prospective data.Aim: This research aims to investigate the impact of an incidentally diagnosed pulmonary embolism on cancer population’ outcomes and to explore their experience of living with cancer and i-PE. The second aim was to explore the role of the key thrombogenic biomarkers as a predictive biomarker of thrombosis.Methods: Mixed method research with critical integrative analysis. A systematic literature review and qualitative analysis to examine patients’ experience of living with cancer-associated thrombosis. A prospective observational case-controlled cohort study with embedded semi-structured interview study to investigate the quality of life and patients’ experience of living with cancer and incidental pulmonary embolism. A retrospective case control-study and scientific analysis of defined biological key factors associated with thrombosis.Results: The diagnosis of cancer-associated thrombosis including incidental pulmonary embolism negatively affect patients’ life, and patients experience this diagnosis in the context of living with cancer. Yet it is a diagnosis that often misattributed, misdiagnosed and associated with lack of information among patients and some of the clinical care professionals. The scientific analysis of the biological biomarkers illustrates the potential role of TF-mRNA as a predictive biomarker for cancer- associated incidental pulmonary embolism and the role of anti-factor ten anticoagulation in reducing the risk of thrombosis.Conclusion: Awareness of patients and care professionals regarding the high risk of thrombosis among cancer population represent an urgent need. Risk assessment tools to predict patients at increased risk of thrombosis would be of value and help target education and reduce the risk of diagnostic overshadowing

Cancer patients’ experiences of the diagnosis and treatment of incidental pulmonary embolism (a qualitative study)

Background: The diagnosis of symptomatic cancer-associated thrombosis often causes distress and alarm for patients, especially for those unaware of the risk, or the signs and symptoms to look out for. There are few data about cancer patients’ experiences of incidentally diagnosed pulmonary embolism (IPE), where lack of warning (recognised signs, symptoms) may cause delayed diagnosis and aggravate distress. Objectives: To explore cancer patients’ experience of the diagnosis of and living with incidental pulmonary embolism treated with anticoagulation. Methods: A qualitative study using modified grounded theory approach. Semi-structured interviews were conducted as part of a mixed- methods prospective observational survey study of consenting patients with IPE. Data were subjected to thematic analysis. The qualitative findings are presented. Findings: Eleven participants were interviewed (mean age 68.3 years, range 38–82 years; various forms of cancer and stages). Three major themes and one cross-cutting theme were generated. Theme (1): IPE is experienced in the context of cancer and concomitant comorbidities. Issues are understood in the shadow of–and often overshadowed by—current serious illness. Theme (2): Being diagnosed with IPE. Misattribution to cancer or other comorbidities caused delay in help-seeking and diagnosis. Theme (3): Coping with anticoagulation. Participants’ incorporated anticoagulation treatment and its effects into their daily routine with acceptance and stoicism. Finally, the cross-cutting theme relates to a lack of information and uncertainty, contributing to distress throughout the experience. Conclusion: The diagnosis of IPE was upsetting and unexpected. Expert and timely information was valued by those with IPE. Education called for about the increased risk of cancer-associated thrombosis and the signs and symptoms to be aware of

Alteration in endothelial permeability occurs in response to the activation of PAR2 by factor Xa but not directly by the TF-factor VIIa complex

Alterations in the endothelial permeability occur in response to the activation of coagulation mechanisms in order to control clot formation. The activation of the protease activated receptors (PAR) can induce signals that regulate such cellular responses. PAR2 is a target for the coagulation factor Xa (fXa) and tissue factor-factor VIIa (TF-fVIIa) complex. By measuring the permeability of dextran blue across endothelial monolayer, we examined the mechanisms linking coagulation and endothelial permeability. Activation of PAR2 using the agonist peptide (PAR2-AP) resulted in increased permeability across the monolayer and was comparable to that obtained with VEGF at 60 min. Incubation of cells with activated factor Xa (fXa) resulted in an initial decrease in permeability by 30 min, but then significantly increased at 60 min. These responses required fXa activity, and were abrogated by incubation of the cells with a PAR2-blocking antibody (SAM11). Activation of PAR2 alone, or inhibition of PAR1, abrogated the initial reduction in permeability. Additionally, inclusion of Rivaroxaban (0.6 µg/ml) significantly inhibited the response to fXa. Finally, incubation of the endothelial monolayers up to 2 h with TF-containing microvesicles derived from MDA-MB-231 cells, in the presence or absence of fVIIa, did not influence the permeability across the monolayers. In conclusion, fXa but not TF-fVIIa is a noteworthy mediator of endothelial permeability. The rapid initial decrease in permeability requires PAR2 and PAR1 which may act to constrain bleeding. The longer-term response is mediated by PAR2 with increased permeability, presumably to enhance clot formation at the site of damage

Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p