Pub Date : 2024-10-16DOI: 10.1016/j.thromres.2024.109183
Nicoletta Erba , Alberto Tosetto , Suha Abdelwahab Abdallah , Martin Langer , Elena Giovanella , Salvatore Lentini , Franco Masini , Alessandro Mocini , Gennarina Portella , Alessandro Cristian Salvati , Alessandro Squizzato , Sophie Testa , Daniela Poli
Introduction
Mechanical heart valve (MHV) replacement requires long-life anticoagulation due to the risk of Prosthetic Valve Dysfunction (PVD) and cardioembolism.
Methods
We report data from a prospective observational study conducted on MHV patients in the Khartoum Salam Centre for Cardiac Surgery built by ‘Emergency,’ an Italian Non-Governmental Organization, to evaluate the occurrence of PVD and associated risk factors.
Results
We prospectively followed 3647 patients, and 38 patients (rate 1.04 × 100 pt-years) had PVD during follow-up. The time in therapeutic range (TTR) among patients without PVD was 53 % (IQR 37–67), and it was 43 % (IQR 19–58) among patients with PVD (p = 0.04). Twenty-three over 38 patients (60.5 %) were symptomatic, 18 (47.4 %) had obstructive valvular stenosis, 24 patients (63.2 %) had INR <2.0 at diagnosis, and 21 patients (55.3 %) had been off warfarin for a long time: 3 patients for 1 week, 1 patient for 2 weeks, and 17 patients for >4 weeks (6 patients were off warfarin from 3 to 12 months). Ten were uncompliant to treatment, and 8 were pregnant women. Ten patients (26.3 %) with PVD had had a previous episode of PVD, and 14 patients (36.8 %) had 2 or more associated risk factors. Only in 6 cases were no associate risk factors found.
Conclusions
Among MHV patients on warfarin treatment with a sub-optimal quality of anticoagulation, the rate of PVD is 1.04 % pt-years, and the most frequent associated risk factor for PVD occurrence is warfarin withdrawal lasting more than one week.
{"title":"Prosthetic valve dysfunction in patients with mechanical heart valves: Results from the Emergency Salam Centre cohort","authors":"Nicoletta Erba , Alberto Tosetto , Suha Abdelwahab Abdallah , Martin Langer , Elena Giovanella , Salvatore Lentini , Franco Masini , Alessandro Mocini , Gennarina Portella , Alessandro Cristian Salvati , Alessandro Squizzato , Sophie Testa , Daniela Poli","doi":"10.1016/j.thromres.2024.109183","DOIUrl":"10.1016/j.thromres.2024.109183","url":null,"abstract":"<div><h3>Introduction</h3><div>Mechanical heart valve (MHV) replacement requires long-life anticoagulation due to the risk of Prosthetic Valve Dysfunction (PVD) and cardioembolism.</div></div><div><h3>Methods</h3><div>We report data from a prospective observational study conducted on MHV patients in the Khartoum Salam Centre for Cardiac Surgery built by ‘Emergency,’ an Italian Non-Governmental Organization, to evaluate the occurrence of PVD and associated risk factors.</div></div><div><h3>Results</h3><div>We prospectively followed 3647 patients, and 38 patients (rate 1.04 × 100 pt-years) had PVD during follow-up. The time in therapeutic range (TTR) among patients without PVD was 53 % (IQR 37–67), and it was 43 % (IQR 19–58) among patients with PVD (<em>p</em> = 0.04). Twenty-three over 38 patients (60.5 %) were symptomatic, 18 (47.4 %) had obstructive valvular stenosis, 24 patients (63.2 %) had INR <2.0 at diagnosis, and 21 patients (55.3 %) had been off warfarin for a long time: 3 patients for 1 week, 1 patient for 2 weeks, and 17 patients for >4 weeks (6 patients were off warfarin from 3 to 12 months). Ten were uncompliant to treatment, and 8 were pregnant women. Ten patients (26.3 %) with PVD had had a previous episode of PVD, and 14 patients (36.8 %) had 2 or more associated risk factors. Only in 6 cases were no associate risk factors found.</div></div><div><h3>Conclusions</h3><div>Among MHV patients on warfarin treatment with a sub-optimal quality of anticoagulation, the rate of PVD is 1.04 % pt-years, and the most frequent associated risk factor for PVD occurrence is warfarin withdrawal lasting more than one week.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109183"},"PeriodicalIF":3.7,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1016/j.thromres.2024.109176
Zixuan Liu , Xu Li , Mingming Chen , Yini Sun , Yuteng Ma , Ming Dong , Liu Cao , Xiaochun Ma
Background
Heparin-binding protein (HBP) levels have been linked to organ failure and may represent an inflammatory biomarker of sepsis. We found disseminated intravascular coagulation (DIC) is associated with higher HBP levels in patients and in in vivo and in vitro models. This prospective, single-center observational study investigated the effects and underlying mechanisms of HBP on the coagulation cascade in sepsis.
Methods
538 patients with sepsis from June 2016 to December 2019 were enrolled. Mechanisms underlying HBP and the coagulation system were investigated in human umbilical vein endothelial cells (HUVEC) and C57 mice.
Results
Increased HBP was associated with sepsis-induced DIC. The optimal cutoff value was 37.5 ng/mL (sensitivity: 56 %, specificity: 65 %). Antithrombin-III (AT-III) activity, plasmin-a2 plasmin inhibitor complex (PIC), procalcitonin (PCT), hemoglobin, and HBP ≥37.5 ng/mL were associated with of DIC occurrence. In HUVECs &C57 mice models, Western blotting, qPCR, and immunohistochemistry analysis showed that the binding between HBP and TGF-β receptor 2 (TGFBR2) caused elevation of plasminogen activator inhibitor-1 (PAI-1) levels. Furthermore, we found that mice stimulated with HBP had higher levels of fibrinogen and D-dimer in the blood. HBP treatment caused the accumulation of fibrinogen in mice lung tissue. Treatment with TGFBR2-small interfering RNAs inhibited the effects.
Conclusion
Patients with sepsis having HBP ≥37.5 ng/mL at admission were more likely to develop DIC. HBP upregulates the expression of fibrinogen and PAI-1 via TGFBR2 and the TGF-β signalling pathway.
{"title":"Heparin-binding protein and sepsis-induced coagulopathy: Modulation of coagulation and fibrinolysis via the TGF-β signalling pathway","authors":"Zixuan Liu , Xu Li , Mingming Chen , Yini Sun , Yuteng Ma , Ming Dong , Liu Cao , Xiaochun Ma","doi":"10.1016/j.thromres.2024.109176","DOIUrl":"10.1016/j.thromres.2024.109176","url":null,"abstract":"<div><h3>Background</h3><div>Heparin-binding protein (HBP) levels have been linked to organ failure and may represent an inflammatory biomarker of sepsis. We found disseminated intravascular coagulation (DIC) is associated with higher HBP levels in patients and in <em>in vivo</em> and <em>in vitro</em> models. This prospective, single-center observational study investigated the effects and underlying mechanisms of HBP on the coagulation cascade in sepsis.</div></div><div><h3>Methods</h3><div>538 patients with sepsis from June 2016 to December 2019 were enrolled. Mechanisms underlying HBP and the coagulation system were investigated in human umbilical vein endothelial cells (HUVEC) and C57 mice.</div></div><div><h3>Results</h3><div>Increased HBP was associated with sepsis-induced DIC. The optimal cutoff value was 37.5 ng/mL (sensitivity: 56 %, specificity: 65 %). Antithrombin-III (AT-III) activity, plasmin-a2 plasmin inhibitor complex (PIC), procalcitonin (PCT), hemoglobin, and HBP ≥37.5 ng/mL were associated with of DIC occurrence. In HUVECs &C57 mice models, Western blotting, qPCR, and immunohistochemistry analysis showed that the binding between HBP and TGF-β receptor 2 (TGFBR2) caused elevation of plasminogen activator inhibitor-1 (PAI-1) levels. Furthermore, we found that mice stimulated with HBP had higher levels of fibrinogen and D-dimer in the blood. HBP treatment caused the accumulation of fibrinogen in mice lung tissue. Treatment with TGFBR2-small interfering RNAs inhibited the effects.</div></div><div><h3>Conclusion</h3><div>Patients with sepsis having HBP ≥37.5 ng/mL at admission were more likely to develop DIC. HBP upregulates the expression of fibrinogen and PAI-1 <em>via</em> TGFBR2 and the TGF-β signalling pathway.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109176"},"PeriodicalIF":3.7,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-13DOI: 10.1016/j.thromres.2024.109184
Hajime Uno , Hong Xiong , Christine Cronin , Deborah Schrag , Jean M. Connors
Introduction
Patients with cancer have an increased risk of developing venous thromboembolism (VTE) but also have an increased risk of both recurrent VTE and bleeding with anticoagulation compared to anticoagulated patients without cancer. CANVAS, a randomized pragmatic effectiveness trial, compared the direct oral anticoagulants a class to low molecular weight heparin for treatment of a new VTE in patients with cancer. The aim of this prespecified secondary analysis of the CANVAS trial is to identify predictors of both recurrent VTE and major bleeding in patients with cancer and new VTE.
Methods
Data from the 671 participants in the analysis population were used to identify predictors of recurrent VTE and bleeding during the 6-month treatment period. Significant predictors identified in the univariable models were carried forward in the multivariable models to identify independent predictors of both risks.
Results
Independent predictors of recurrent VTE include ECOG performance status ≥2 (HR, 3.19 [95 % CI, 1.45–7.02]; P < .005), presence of metastatic disease (HR, 2.57 [95 % CI, 1.14–5.80]; P = .023), treatment with bevacizumab (HR, 2.50 [95 % CI, 1.04–5.99]; P = .041), and deep vein thrombosis without pulmonary embolus as index VTE (HR, 1.86 [95 % CI, 1.04–3.33]; P = .037). Independent predictors of major bleeding include serum albumin <3.5 g/dL (HR 1.97 [95 % CI, 1.02–3.79]; P = .044) and metastatic disease (HR 2.80 [95 % CI, 1.08–7.22]; P = .034).
Conclusion
Findings from this pre-specified analysis of the CANVAS trial identified risk factors for recurrent VTE and major bleeding in a population of participants with cancer and new VTE that reflect current oncology clinical practice. Results can be used to identify at risk patients in practice and inform new risk prediction models to improve the care of these patients.
{"title":"Predictors of recurrent venous thromboembolism and major bleeding in patients with cancer: A secondary analysis of the CANVAS trial","authors":"Hajime Uno , Hong Xiong , Christine Cronin , Deborah Schrag , Jean M. Connors","doi":"10.1016/j.thromres.2024.109184","DOIUrl":"10.1016/j.thromres.2024.109184","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with cancer have an increased risk of developing venous thromboembolism (VTE) but also have an increased risk of both recurrent VTE and bleeding with anticoagulation compared to anticoagulated patients without cancer. CANVAS, a randomized pragmatic effectiveness trial, compared the direct oral anticoagulants a class to low molecular weight heparin for treatment of a new VTE in patients with cancer. The aim of this prespecified secondary analysis of the CANVAS trial is to identify predictors of both recurrent VTE and major bleeding in patients with cancer and new VTE.</div></div><div><h3>Methods</h3><div>Data from the 671 participants in the analysis population were used to identify predictors of recurrent VTE and bleeding during the 6-month treatment period. Significant predictors identified in the univariable models were carried forward in the multivariable models to identify independent predictors of both risks.</div></div><div><h3>Results</h3><div>Independent predictors of recurrent VTE include ECOG performance status ≥2 (HR, 3.19 [95 % CI, 1.45–7.02]; <em>P</em> < .005), presence of metastatic disease (HR, 2.57 [95 % CI, 1.14–5.80]; <em>P</em> = .023), treatment with bevacizumab (HR, 2.50 [95 % CI, 1.04–5.99]; <em>P</em> = .041), and deep vein thrombosis without pulmonary embolus as index VTE (HR, 1.86 [95 % CI, 1.04–3.33]; <em>P</em> = .037). Independent predictors of major bleeding include serum albumin <3.5 g/dL (HR 1.97 [95 % CI, 1.02–3.79]; <em>P</em> = .044) and metastatic disease (HR 2.80 [95 % CI, 1.08–7.22]; <em>P</em> = .034).</div></div><div><h3>Conclusion</h3><div>Findings from this pre-specified analysis of the CANVAS trial identified risk factors for recurrent VTE and major bleeding in a population of participants with cancer and new VTE that reflect current oncology clinical practice. Results can be used to identify at risk patients in practice and inform new risk prediction models to improve the care of these patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109184"},"PeriodicalIF":3.7,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142434203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.thromres.2024.109182
Rasmus Søgaard Hansen , Rasmus Bank Lynggaard , Martin Sundahl Laursen , Freja Maack Lykke , Pernille Just Vinholt
{"title":"Identification of hematuria with a natural language processing model and validation of hematuria diagnosecodes","authors":"Rasmus Søgaard Hansen , Rasmus Bank Lynggaard , Martin Sundahl Laursen , Freja Maack Lykke , Pernille Just Vinholt","doi":"10.1016/j.thromres.2024.109182","DOIUrl":"10.1016/j.thromres.2024.109182","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109182"},"PeriodicalIF":3.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.thromres.2024.109181
Marta Aguilar Rodríguez , Sofía Pérez-Alenda , Juan J. Carrasco , Juan Eduardo Megías-Vericat , Santiago Bonanad , Felipe Querol , Ana Chimeno-Hernández
Introduction
A comprehensive treatment for patients with haemophilia (PwH) should focus on how the disease interferes with their mental, emotional and social environment to analyse if all the therapeutic efforts invested in their physical status have positive impact on a life worth living.
Aim
To analyse the correlation between the physical status of a cohort of adults with haemophilia and their mental, emotional and social states regarding their treatment modality; Also, to investigate which variables are most related to quality of life (QoL), joint health and emotional, mental and social states.
Methods
In this cross-sectional, 102 adults with haemophilia divided into a prophylactic group (G1, n = 77) and on-demand group (G2, n = 25) were included. Demographic and clinical characteristics, health joint (HJHS), presence of synovitis with ultrasound, self-perceived functionality (HAL) and QoL (A36-HaemoQoL), were analysed.
Results
In G1 all the variables that defined the physical status correlated (rho: 0.33 to 0.72) to the mental and social spheres. The emotional state correlated with the self-perceived ones. In G2 physical status did not correlate with the three states. According to the regression models, HAL was the variable that most influenced the QoL (together with the bleedings in the last year, R2 = 0.61), emotional (R2 = 0.16), mental (together with HJHS, R2 = 0.41) and social states (R2 = 0.39). In addition, the HJHS was influenced by synovitis, HAL, mental health, age and the bleeding history (R2 = 0.83).
Conclusion
Emotional, mental and social states of PwH in prophylaxis are correlated to their physical status, being the self-perceived functionality the variable that most influenced in their QoL.
{"title":"Mental, emotional and social dimensions of quality of life and their relationship with physical and functional status in adults with haemophilia","authors":"Marta Aguilar Rodríguez , Sofía Pérez-Alenda , Juan J. Carrasco , Juan Eduardo Megías-Vericat , Santiago Bonanad , Felipe Querol , Ana Chimeno-Hernández","doi":"10.1016/j.thromres.2024.109181","DOIUrl":"10.1016/j.thromres.2024.109181","url":null,"abstract":"<div><h3>Introduction</h3><div>A comprehensive treatment for patients with haemophilia (PwH) should focus on how the disease interferes with their mental, emotional and social environment to analyse if all the therapeutic efforts invested in their physical status have positive impact on a life worth living.</div></div><div><h3>Aim</h3><div>To analyse the correlation between the physical status of a cohort of adults with haemophilia and their mental, emotional and social states regarding their treatment modality; Also, to investigate which variables are most related to quality of life (QoL), joint health and emotional, mental and social states.</div></div><div><h3>Methods</h3><div>In this cross-sectional, 102 adults with haemophilia divided into a prophylactic group (G1, <em>n</em> = 77) and on-demand group (G2, <em>n</em> = 25) were included. Demographic and clinical characteristics, health joint (HJHS), presence of synovitis with ultrasound, self-perceived functionality (HAL) and QoL (A36-HaemoQoL), were analysed.</div></div><div><h3>Results</h3><div>In G1 all the variables that defined the physical status correlated (rho: 0.33 to 0.72) to the mental and social spheres. The emotional state correlated with the self-perceived ones. In G2 physical status did not correlate with the three states. According to the regression models, HAL was the variable that most influenced the QoL (together with the bleedings in the last year, R<sup>2</sup> = 0.61), emotional (R<sup>2</sup> = 0.16), mental (together with HJHS, R<sup>2</sup> = 0.41) and social states (R<sup>2</sup> = 0.39). In addition, the HJHS was influenced by synovitis, HAL, mental health, age and the bleeding history (R<sup>2</sup> = 0.83).</div></div><div><h3>Conclusion</h3><div>Emotional, mental and social states of PwH in prophylaxis are correlated to their physical status, being the self-perceived functionality the variable that most influenced in their QoL.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109181"},"PeriodicalIF":3.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-12DOI: 10.1016/j.thromres.2024.109180
Jose Manuel Calvo Villas , Manuel Rodríguez López , Jorge Cuesta Tovar , Santiago Bonanad Boix , Juan Carlos Reverter Calatayud , María Teresa Álvarez-Román
{"title":"Suitability and readiness assessment of organizational resources for the implementation of gene therapy in hemophilia in Spain and Portugal: A survey-based study","authors":"Jose Manuel Calvo Villas , Manuel Rodríguez López , Jorge Cuesta Tovar , Santiago Bonanad Boix , Juan Carlos Reverter Calatayud , María Teresa Álvarez-Román","doi":"10.1016/j.thromres.2024.109180","DOIUrl":"10.1016/j.thromres.2024.109180","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109180"},"PeriodicalIF":3.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1016/j.thromres.2024.109179
Winnifer Briceño , Sara González , Carmen Rodríguez , Ana Castillo , Ignacio Jara , Laura Lago , Edwin Yong , Alfonso Muriel , Álvaro Dubois-Silva , Behnood Bikdeli , Gema Díaz , David Jiménez
{"title":"Prognostic significance of saddle pulmonary embolism a post hoc analysis of the PROTECT cohort study","authors":"Winnifer Briceño , Sara González , Carmen Rodríguez , Ana Castillo , Ignacio Jara , Laura Lago , Edwin Yong , Alfonso Muriel , Álvaro Dubois-Silva , Behnood Bikdeli , Gema Díaz , David Jiménez","doi":"10.1016/j.thromres.2024.109179","DOIUrl":"10.1016/j.thromres.2024.109179","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109179"},"PeriodicalIF":3.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-05DOI: 10.1016/j.thromres.2024.109177
Eugene Yuriditsky , Robert S. Zhang , Peter Zhang , James M. Horowitz , Samuel Bernard , Allison A. Greco , Radu Postelnicu , Vikramjit Mukherjee , Kerry Hena , Lindsay Elbaum , Carlos L. Alviar , Norma M. Keller , Sripal Bangalore
Background and Aims
Patients with intermediate-risk pulmonary embolism (PE) commonly present with a significantly reduced cardiac index (CI). However, the identification of this more severe profile requires invasive hemodynamic monitoring. Whether inferior vena cava (IVC) contrast reflux, as a marker of worse right ventricular function, can predict invasive hemodynamics has not been explored.
Methods
This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization. CT pulmonary angiograms were reviewed, and contrast reflux was graded as no/minimal reflux (limited to the IVC) or substantial (opacification including hepatic veins) based on an established scale.
Results
Substantial contrast reflux was present in 29 of 85 patients (34 %) and associated with a lower CI (1.8 ± 0.4 L/min/m2 v. 2.6 ± 1.0 L/min/m2, p < 0.001), higher pulmonary artery systolic pressure (53.2 ± 19.5 mmHg v. 44.0 ± 12.1 mmHg, p = 0.025), and worse right ventricular systolic function. An IVC contrast reflux grade > 3 was a significant predictor for a CI ≤2.2 L/min/m2 (OR: 22.5, 95 % CI: 4.8, 104.4, p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for substantial contrast reflux for a CI ≤2.2 L/min/m2 were 62.6 %, 93.1 %, 94.6 %, and 56.2 %, respectively. These findings remained significant in a multivariable model and were similar when isolating for intermediate-risk patients (n = 72, 85 %).
Conclusions
The degree of contrast reflux is highly specific for a reduced cardiac index in PE even when isolating for intermediate-risk patients. Real-time prediction of a hemodynamic profile may have added value in the risk-stratification of PE.
背景和目的：中危肺栓塞（PE）患者通常会出现心脏指数（CI）明显降低的情况。然而，识别这种更严重的情况需要有创血液动力学监测。下腔静脉（IVC）造影剂反流作为右心室功能恶化的标志，是否能预测有创血流动力学尚未进行探讨：这是一项为期 3 年的单中心回顾性研究，研究对象是接受机械血栓切除术并同时接受肺动脉导管检查的连续 PE 患者。对 CT 肺血管造影进行复查，并根据既定标准将造影剂反流分为无/轻微反流（仅限于 IVC）或大量反流（包括肝静脉的不透明）：85 例患者中有 29 例（34%）存在大量造影剂回流，且与较低的 CI 有关（1.8 ± 0.4 L/min/m2 v. 2.6 ± 1.0 L/min/m2，P 3），CI ≤2.2 L/min/m2 的显著预测因子（OR：22.5，95 % CI：4.8，104.4，P 2 分别为 62.6%、93.1%、94.6% 和 56.2%）。这些结果在多变量模型中仍有意义，在分离中危患者（n = 72，85%）时也类似：结论：造影剂反流程度对 PE 患者心脏指数降低具有高度特异性，即使将中危患者分离出来也是如此。实时预测血液动力学特征可能会为 PE 的风险分级带来更多价值。
{"title":"Inferior vena cava contrast reflux grade is associated with a reduced cardiac index in acute pulmonary embolism","authors":"Eugene Yuriditsky , Robert S. Zhang , Peter Zhang , James M. Horowitz , Samuel Bernard , Allison A. Greco , Radu Postelnicu , Vikramjit Mukherjee , Kerry Hena , Lindsay Elbaum , Carlos L. Alviar , Norma M. Keller , Sripal Bangalore","doi":"10.1016/j.thromres.2024.109177","DOIUrl":"10.1016/j.thromres.2024.109177","url":null,"abstract":"<div><h3>Background and Aims</h3><div>Patients with intermediate-risk pulmonary embolism (PE) commonly present with a significantly reduced cardiac index (CI). However, the identification of this more severe profile requires invasive hemodynamic monitoring. Whether inferior vena cava (IVC) contrast reflux, as a marker of worse right ventricular function, can predict invasive hemodynamics has not been explored.</div></div><div><h3>Methods</h3><div>This was a single-center retrospective study over a 3-year period of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization. CT pulmonary angiograms were reviewed, and contrast reflux was graded as no/minimal reflux (limited to the IVC) or substantial (opacification including hepatic veins) based on an established scale.</div></div><div><h3>Results</h3><div>Substantial contrast reflux was present in 29 of 85 patients (34 %) and associated with a lower CI (1.8 ± 0.4 L/min/m<sup>2</sup> v. 2.6 ± 1.0 L/min/m<sup>2</sup>, <em>p</em> < 0.001), higher pulmonary artery systolic pressure (53.2 ± 19.5 mmHg v. 44.0 ± 12.1 mmHg, <em>p</em> = 0.025), and worse right ventricular systolic function. An IVC contrast reflux grade > 3 was a significant predictor for a CI ≤2.2 L/min/m<sup>2</sup> (OR: 22.5, 95 % CI: 4.8, 104.4, <em>p</em> < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value for substantial contrast reflux for a CI ≤2.2 L/min/m<sup>2</sup> were 62.6 %, 93.1 %, 94.6 %, and 56.2 %, respectively. These findings remained significant in a multivariable model and were similar when isolating for intermediate-risk patients (<em>n</em> = 72, 85 %).</div></div><div><h3>Conclusions</h3><div>The degree of contrast reflux is highly specific for a reduced cardiac index in PE even when isolating for intermediate-risk patients. Real-time prediction of a hemodynamic profile may have added value in the risk-stratification of PE.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109177"},"PeriodicalIF":3.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1016/j.thromres.2024.109178
Amir Asgari , Aleksandra Franczak , Alex Herchen , Glen C. Jickling , Paul Jurasz
Background
Platelet-rich microvascular thrombi are common in severe COVID-19. Endogenous nitric oxide (NO)-signaling limits thrombus formation and previously we identified platelet subpopulations with a differential ability to produce NO based on the presence or absence of endothelial nitric oxide synthase (eNOS). eNOS expression is counter-regulated by cytokines, and COVID-19-associated immune/inflammatory responses may affect the transcriptome profile of megakaryocytes and their platelet progeny.
Objectives
We investigated whether the percentage of eNOS-negative to eNOS-positive platelets increases in COVID-19 patients and whether this change may be due to the actions of pro-inflammatory cytokines on megakaryocytes.
Methods
Platelets were isolated from hospitalized COVID-19 patients and COVID-19-negative controls. Platelet eNOS was measured by flow cytometry and plasma inflammatory cytokines by ELISA. Megakaryocytes from eNOS-GFP transgenic mice and the Meg-01 cell line were characterized to identify an appropriate model to study eNOS-based platelet subpopulation formation in response to inflammatory cytokines.
Results
COVID-19 patients demonstrated a significant increase in eNOS-negative and a concomitant decrease in eNOS-positive platelets compared to controls, and this change was associated with disease severity as assessed by ICU admission. A higher eNOS-negative to –positive platelet percentage was associated with enhanced platelet activation as measured by surface CD62P. Accordingly, COVID-19 patients demonstrated higher TNF-α, IL-6, and IL-1β plasma concentrations than controls. Inflammatory cytokines associated with COVID-19 promoted eNOS-negative Meg-01 formation and enhanced subsequent eNOS-negative platelet-like particle formation.
Conclusions
COVID-19 patients have a higher percentage of eNOS-negative to –positive platelets, likely as a result of inflammatory response reducing megakaryocyte eNOS expression, which predisposes to thrombosis.
{"title":"Elevated levels of pro-thrombotic eNOS-negative platelets in COVID-19 patients","authors":"Amir Asgari , Aleksandra Franczak , Alex Herchen , Glen C. Jickling , Paul Jurasz","doi":"10.1016/j.thromres.2024.109178","DOIUrl":"10.1016/j.thromres.2024.109178","url":null,"abstract":"<div><h3>Background</h3><div>Platelet-rich microvascular thrombi are common in severe COVID-19. Endogenous nitric oxide (NO)-signaling limits thrombus formation and previously we identified platelet subpopulations with a differential ability to produce NO based on the presence or absence of endothelial nitric oxide synthase (eNOS). eNOS expression is counter-regulated by cytokines, and COVID-19-associated immune/inflammatory responses may affect the transcriptome profile of megakaryocytes and their platelet progeny.</div></div><div><h3>Objectives</h3><div>We investigated whether the percentage of eNOS-negative to eNOS-positive platelets increases in COVID-19 patients and whether this change may be due to the actions of pro-inflammatory cytokines on megakaryocytes.</div></div><div><h3>Methods</h3><div>Platelets were isolated from hospitalized COVID-19 patients and COVID-19-negative controls. Platelet eNOS was measured by flow cytometry and plasma inflammatory cytokines by ELISA. Megakaryocytes from eNOS-GFP transgenic mice and the Meg-01 cell line were characterized to identify an appropriate model to study eNOS-based platelet subpopulation formation in response to inflammatory cytokines.</div></div><div><h3>Results</h3><div>COVID-19 patients demonstrated a significant increase in eNOS-negative and a concomitant decrease in eNOS-positive platelets compared to controls, and this change was associated with disease severity as assessed by ICU admission. A higher eNOS-negative to –positive platelet percentage was associated with enhanced platelet activation as measured by surface CD62P. Accordingly, COVID-19 patients demonstrated higher TNF-α, IL-6, and IL-1β plasma concentrations than controls. Inflammatory cytokines associated with COVID-19 promoted eNOS-negative Meg-01 formation and enhanced subsequent eNOS-negative platelet-like particle formation.</div></div><div><h3>Conclusions</h3><div>COVID-19 patients have a higher percentage of eNOS-negative to –positive platelets, likely as a result of inflammatory response reducing megakaryocyte eNOS expression, which predisposes to thrombosis.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109178"},"PeriodicalIF":3.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.thromres.2024.109155
{"title":"Abstracts from the CanVECTOR 2024 Annual Conference October 25th, 2024","authors":"","doi":"10.1016/j.thromres.2024.109155","DOIUrl":"10.1016/j.thromres.2024.109155","url":null,"abstract":"","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"242 ","pages":"Article 109155"},"PeriodicalIF":3.7,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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