Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100144
L.A. Ciuffini , A. Delluc , T.F. Wang , C. Lodigiani , M. Carrier
Background
Atrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy [direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA)] for stroke and systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA).
Methods
A systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3).
Results
Of the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)).
Conclusion
DOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.
{"title":"Evaluating efficacy and safety of oral anticoagulation in adult patients with atrial fibrillation and cancer: A systemic review and meta-analysis","authors":"L.A. Ciuffini , A. Delluc , T.F. Wang , C. Lodigiani , M. Carrier","doi":"10.1016/j.tru.2023.100144","DOIUrl":"10.1016/j.tru.2023.100144","url":null,"abstract":"<div><h3>Background</h3><p>Atrial fibrillation (AF) is common among patients with cancer. Patients with cancer and AF require anticoagulant therapy [direct oral anticoagulants (DOAC) or vitamin K antagonist (VKA)] for stroke and systemic embolism (SE) prevention. We sought to assess the rates of stroke/SE and major bleeding in patients with cancer and AF on oral anticoagulant therapy (DOAC or VKA).</p></div><div><h3>Methods</h3><p>A systematic search of MEDLINE and EMBASE was conducted. The primary efficacy and safety outcome were stroke/SE and major bleeding (as per the International Society on Thrombosis and Haemostasis definition), respectively. Incidence rates (IR) were pooled using random effects model (event per 100 patient-years). Incidence rate ratios (IRR) were computed using a Poisson regression model with associated 95% confidence intervals (CI) using R software (version 4.0.3).</p></div><div><h3>Results</h3><p>Of the total 2,153 article records that were screened, 22 observational studies from 12 different countries were included in the meta-analysis (n = 94,980 patients). The IR of stroke/SE was 1.81 (95% CI: 0.89 to 3.68) and 3.41 (95% CI: 1.38 to 8.41) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.63 (95%CI: 0.47–0.84)). The IR of major bleeding was 2.59 (95%CI: 1.54 to 4.38) and 3.60 (95% CI: 1.68 to 7.71) per 100 patient-years for patients receiving a DOAC and VKA, respectively (IRR: 0.76 (95% CI: 0.55 to 1.04)).</p></div><div><h3>Conclusion</h3><p>DOACs compared to VKA seem to provide a significant reduction in the risk of stroke/SE and a good risk-benefit ratio profile for safety outcomes in this patient population.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100144"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45935491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100142
Inge H.Y. Luu , Jacqueline Buijs , Jasenko Krdzalic , Martijn D. de Kruif , Guy J.M. Mostard , Hugo ten Cate , Tom P.J. Dormans , Remy L.M. Mostard , Math P.G. Leers , Daan J.L. van Twist
Introduction
Pulmonary embolism (PE) is a frequent complication in COVID-19. However, the influence of PE on the prognosis of COVID-19 remains unclear as previous studies were affected by misclassification bias. Therefore, we evaluated a cohort of COVID-19 patients whom all underwent systematic screening for PE (thereby avoiding misclassification) and compared clinical outcomes between patients with and without PE.
Materials and methods
We included all COVID-19 patients who were admitted through the ED between April 2020 and February 2021. All patients underwent systematic work-up for PE in the ED using the YEARS-algorithm. The primary outcome was a composite of in-hospital mortality and ICU admission. We also evaluated long-term outcomes including PE occurrence within 90 days after discharge and one-year all-cause mortality.
Results
637 ED patients were included in the analysis. PE was diagnosed in 46 of them (7.2%). The occurrence of the primary outcome did not differ between patients with PE and those without (28.3% vs. 26.9%, p = 0.68). The overall rate of PE diagnosed in-hospital (after an initial negative PE screening in the ED) and in the first 90 days after discharge was 3.9% and 1.2% respectively. One-year all-cause mortality was similar between patients with and without PE (26.1% vs. 24.4%, p = 0.83).
Conclusions
In a cohort of COVID-19 patients who underwent systematic PE screening in the ED, we found no differences in mortality rate and ICU admissions between patients with and without PE. This may indicate that proactive PE screening, and thus timely diagnosis and treatment of PE, may limit further clinical deterioration and associated mortality in COVID-19 patients.
肺栓塞(PE)是COVID-19的常见并发症。然而，由于以往的研究受到误分类偏倚的影响，PE对COVID-19预后的影响尚不清楚。因此，我们评估了一组COVID-19患者，他们都进行了系统的PE筛查(从而避免了错误分类)，并比较了有PE和没有PE的患者的临床结果。材料和方法我们纳入了2020年4月至2021年2月期间通过急诊科入院的所有COVID-19患者。所有患者在急诊科均采用year -算法对PE进行了系统检查。主要结局是住院死亡率和ICU住院率的综合。我们还评估了长期预后，包括出院后90天内PE的发生率和一年内全因死亡率。结果637例ED患者纳入分析。其中46例(7.2%)诊断为PE。PE患者与非PE患者的主要结局发生率无差异(28.3% vs. 26.9%， p = 0.68)。住院(在急诊科进行初始PE阴性筛查后)和出院后90天内PE诊断的总体比率分别为3.9%和1.2%。有和没有PE的患者一年全因死亡率相似(26.1% vs. 24.4%， p = 0.83)。结论在一组在急诊科接受系统PE筛查的COVID-19患者中，我们发现PE患者和非PE患者的死亡率和ICU入院率没有差异。这可能表明，积极的PE筛查，从而及时诊断和治疗PE，可能会限制COVID-19患者的进一步临床恶化和相关死亡率。
{"title":"Pulmonary embolism in hospitalized COVID-19 patients: Short- and long-term clinical outcomes","authors":"Inge H.Y. Luu , Jacqueline Buijs , Jasenko Krdzalic , Martijn D. de Kruif , Guy J.M. Mostard , Hugo ten Cate , Tom P.J. Dormans , Remy L.M. Mostard , Math P.G. Leers , Daan J.L. van Twist","doi":"10.1016/j.tru.2023.100142","DOIUrl":"10.1016/j.tru.2023.100142","url":null,"abstract":"<div><h3>Introduction</h3><p>Pulmonary embolism (PE) is a frequent complication in COVID-19. However, the influence of PE on the prognosis of COVID-19 remains unclear as previous studies were affected by misclassification bias. Therefore, we evaluated a cohort of COVID-19 patients whom all underwent systematic screening for PE (thereby avoiding misclassification) and compared clinical outcomes between patients with and without PE.</p></div><div><h3>Materials and methods</h3><p>We included all COVID-19 patients who were admitted through the ED between April 2020 and February 2021. All patients underwent systematic work-up for PE in the ED using the YEARS-algorithm. The primary outcome was a composite of in-hospital mortality and ICU admission. We also evaluated long-term outcomes including PE occurrence within 90 days after discharge and one-year all-cause mortality.</p></div><div><h3>Results</h3><p>637 ED patients were included in the analysis. PE was diagnosed in 46 of them (7.2%). The occurrence of the primary outcome did not differ between patients with PE and those without (28.3% vs. 26.9%, <em>p</em> = 0.68). The overall rate of PE diagnosed in-hospital (after an initial negative PE screening in the ED) and in the first 90 days after discharge was 3.9% and 1.2% respectively. One-year all-cause mortality was similar between patients with and without PE (26.1% vs. 24.4%, <em>p</em> = 0.83).</p></div><div><h3>Conclusions</h3><p>In a cohort of COVID-19 patients who underwent systematic PE screening in the ED, we found no differences in mortality rate and ICU admissions between patients with and without PE. This may indicate that proactive PE screening, and thus timely diagnosis and treatment of PE, may limit further clinical deterioration and associated mortality in COVID-19 patients.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100142"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49167797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100141
Marta Szlaszynska , Gabor Forgo , Riccardo M. Fumagalli , Daniela Mazzaccaro , Giovanni Nano , Nils Kucher , Tim Sebastian , Stefano Barco
Introduction
Intravenous drug use continues to pose a substantial burden worldwide and little is known about the risk of venous thromboembolism (VTE) and its sequelae in people who inject drugs (PWID).
Methods
A systematic literature search was conducted on the prevalence of VTE and chronic venous disease in intravenous drug users, as well as on the prevalence of intravenous drug use among selected VTE patients. Two reviewers independently selected the articles and appraised their quality. A random-effect meta-analysis was performed to pool risks across studies.
Results
We included 18 studies with a total of 7691 patients. The overall prevalence of VTE among PWID was 29% (95%CI: 19–40%). Among patients diagnosed with VTE, 15% (95%CI: 10–20%) were PWID. Similar rates were confirmed in more recent studies published in the past decade, although these studies are often based on the general population from higher-risk areas. Reported rates of chronic venous disease ranged between 58% and 61%. The majority of the included studies had a low to moderate quality of evidence. We could not exclude a selection bias in the studies in geographical regions with high intravenous drug use prevalence.
Conclusion
VTE and chronic venous disease appear to be common and understudied complications of injective drug use. National programs for PWID patients should also focus on early and late VTE-associated complications.
{"title":"Venous thromboembolism and chronic venous disease among people who inject drugs: A systematic review and meta-analysis","authors":"Marta Szlaszynska , Gabor Forgo , Riccardo M. Fumagalli , Daniela Mazzaccaro , Giovanni Nano , Nils Kucher , Tim Sebastian , Stefano Barco","doi":"10.1016/j.tru.2023.100141","DOIUrl":"10.1016/j.tru.2023.100141","url":null,"abstract":"<div><h3>Introduction</h3><p>Intravenous drug use continues to pose a substantial burden worldwide and little is known about the risk of venous thromboembolism (VTE) and its sequelae in people who inject drugs (PWID).</p></div><div><h3>Methods</h3><p>A systematic literature search was conducted on the prevalence of VTE and chronic venous disease in intravenous drug users, as well as on the prevalence of intravenous drug use among selected VTE patients. Two reviewers independently selected the articles and appraised their quality. A random-effect meta-analysis was performed to pool risks across studies.</p></div><div><h3>Results</h3><p>We included 18 studies with a total of 7691 patients. The overall prevalence of VTE among PWID was 29% (95%CI: 19–40%). Among patients diagnosed with VTE, 15% (95%CI: 10–20%) were PWID. Similar rates were confirmed in more recent studies published in the past decade, although these studies are often based on the general population from higher-risk areas. Reported rates of chronic venous disease ranged between 58% and 61%. The majority of the included studies had a low to moderate quality of evidence. We could not exclude a selection bias in the studies in geographical regions with high intravenous drug use prevalence.</p></div><div><h3>Conclusion</h3><p>VTE and chronic venous disease appear to be common and understudied complications of injective drug use. National programs for PWID patients should also focus on early and late VTE-associated complications.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100141"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43915509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100143
Jack T. Seki , Reem Alsibai , Eshetu G. Atenafu , Ruiqi Chen , Hassan Sibai
Summary/background
Native Ecoli-Asparaginase (NEA)-containing regimens is an integral part of the ALL-treatment protocol for pediatric and young adults. By observation, polyethylene glycol-asparaginase (PEG-a) recipients have experienced heightened rates of thrombosis. We conducted a meta-analysis investigating which ASP formulation, instigated thrombosis more intensely. We examined potential risk factors and whether LMWH intervention influence VTE prevention.
Methods
209 studies were reviewed and analyzed. 18 PEG-a- and 15 NEA-containing studies are selected. Of these, 23 Non-LMWH and 10 LMWH thromboprophylaxis interventions are used for VTE rates comparison. One single-center and four comparative studies sought to determine the impact of LMWH on VTE prevention.
Results
The combined data set indicated a significantly higher proportion of VTE incidences in the PEG-a population compared to the NEA recipients. The non-LMWH study data showed a significantly higher proportion of VTE incidences in the PEG-a recipients. In the LMWH-containing data, PEG-a recipients had only slightly higher VTE outcome. LMWH has a favorable effect on VTE prevention as shown by the Forest plot. ASPs exposure and age ≥10 years ranked high-risk for VTE.
Conclusion
PEG-a- compared to NEA-treated adult patients are at significantly higher risk of developing VTE. LMWH demonstrated a protective effect on VTE prevention.
{"title":"Is native E coli- or Peg-ASP more thrombogenic in adult ALL? A systematic review and meta-analysis","authors":"Jack T. Seki , Reem Alsibai , Eshetu G. Atenafu , Ruiqi Chen , Hassan Sibai","doi":"10.1016/j.tru.2023.100143","DOIUrl":"10.1016/j.tru.2023.100143","url":null,"abstract":"<div><h3>Summary/background</h3><p>Native Ecoli-Asparaginase (NEA)-containing regimens is an integral part of the ALL-treatment protocol for pediatric and young adults. By observation, polyethylene glycol-asparaginase (PEG-a) recipients have experienced heightened rates of thrombosis. We conducted a meta-analysis investigating which ASP formulation, instigated thrombosis more intensely. We examined potential risk factors and whether LMWH intervention influence VTE prevention.</p></div><div><h3>Methods</h3><p>209 studies were reviewed and analyzed. 18 PEG-a- and 15 NEA-containing studies are selected. Of these, 23 Non-LMWH and 10 LMWH thromboprophylaxis interventions are used for VTE rates comparison. One single-center and four comparative studies sought to determine the impact of LMWH on VTE prevention.</p></div><div><h3>Results</h3><p>The combined data set indicated a significantly higher proportion of VTE incidences in the PEG-a population compared to the NEA recipients. The non-LMWH study data showed a significantly higher proportion of VTE incidences in the PEG-a recipients. In the LMWH-containing data, PEG-a recipients had only slightly higher VTE outcome. LMWH has a favorable effect on VTE prevention as shown by the Forest plot. ASPs exposure and age ≥10 years ranked high-risk for VTE.</p></div><div><h3>Conclusion</h3><p>PEG-a- compared to NEA-treated adult patients are at significantly higher risk of developing VTE. LMWH demonstrated a protective effect on VTE prevention.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100143"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47503777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100145
Susanna Calling , Peter Nymberg , Veronica Milos Nymberg , Peter J. Svensson , Johan Elf , Gunnar Engström , Bengt Zöller
Background
Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE.
Objectives
To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study.
Methods
As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE.
Results
Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders.
Conclusion
Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results.
{"title":"Lung function, respiratory symptoms and incident venous thromboembolism during a 44-year follow-up","authors":"Susanna Calling , Peter Nymberg , Veronica Milos Nymberg , Peter J. Svensson , Johan Elf , Gunnar Engström , Bengt Zöller","doi":"10.1016/j.tru.2023.100145","DOIUrl":"10.1016/j.tru.2023.100145","url":null,"abstract":"<div><h3>Background</h3><p>Chronic obstructive pulmonary disease (COPD) and infections are risk factors for venous thromboembolism (VTE), but the reasons behind the associations are not fully known. Few studies have investigated whether lung function and respiratory symptoms in individuals without COPD are associated with VTE.</p></div><div><h3>Objectives</h3><p>To study the incidence of VTE in individuals without COPD and other major VTE risk factors, in relation to baseline lung function and respiratory symptoms, through a 44-year follow-up prospective cohort study.</p></div><div><h3>Methods</h3><p>As part of a health screening program, a total of 20,253 men and 7361 women underwent a baseline examination from 1974 to 1992, including a spirometry test and a self-administered questionnaire about respiratory symptoms, e.g., chronic bronchitis, cough, phlegm, and dyspnoea. Lung function was assessed through quartiles of forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC). Through linkage with national registers, all individuals were followed for incidence of VTE.</p></div><div><h3>Results</h3><p>Respiratory symptoms (cough and dyspnoea) at baseline were associated with an increased risk of incident VTE in women after adjustments for age, height, BMI, smoking status, varicose veins, and FEV1/FVC. The adjusted hazard ratio in relation to chronic bronchitis was 1.57 (95% confidence interval 1.17–2.11). Poor lung function was not associated with an increased risk of VTE after adjustments for potential confounders.</p></div><div><h3>Conclusion</h3><p>Women with respiratory symptoms of cough and dyspnoea without COPD have an increased risk of VTE, independent of lung function and major VTE risk factors. Further studies are needed to confirm the association and to study the clinical applicability of the results.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48099425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-01DOI: 10.1016/j.tru.2023.100140
Lejan Schultinge , Anne-Marije Hulshof , Danihel van Neerven , Mark M.G. Mulder , Jan-Willem E.M. Sels , Hendrina P.M.G. Hulsewe , Gehardus J.A.J.M. Kuiper , Renske H. Olie , Hugo ten Cate , Iwan C.C. van der Horst , Bas C.T. van Bussel , Yvonne M.C. Henskens
Background
Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays.
Objective
To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH.
Material and methods
A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics.
Results
A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3–1.4]) compared to patients treated with LMWH (1.0 [1.0–1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001–0.62)) compared to therapeutic LMWH (0.09 (0.05–0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849–1.00), 0.851(0.702–1.000), and 0.645(0.465–0.826) for the CT ratio, aPTT, and anti-Xa, respectively.
Conclusion
The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.
背景COVID-19危重患者存在静脉血栓栓塞(VTE)风险。因此，他们接受血栓预防，适当时，治疗性未分离肝素(UFH)或低分子量肝素(LMWH)。为了监测COVID-19疾病中的肝素，全血旋转血栓弹性测定法(ROTEM)可能是aPTT和抗xa检测的一种有希望的替代方法。目的评价机械通气治疗的新型冠状病毒肺炎(COVID-19)患者联合应用低分子肝素和UFH治疗的ROTEM、tem /HEPTEM比值。材料与方法对马斯特里赫特重症监护(Maastricht)前瞻性队列中机械通气的Covid -19患者进行a亚队列研究。采用单变量和多变量线性回归分析和受试者工作特征评估UFH或低分子肝素(nadroparin)治疗剂量后的抗xa、aPTT和ROTEM测量。结果共纳入98例患者，其中UFH治疗82例，低分子肝素治疗16例。与低分子肝素治疗的患者(1.0[1.0 - 1.1])相比，使用UFH治疗的患者rotem测量的INTEM/HEPTEM CT比值(1.4[1.3-1.4])更高，p <0.001)。aPTT和anti-Xa均与CT比值相关。然而，与抗xa试验相比，UFH患者的β-回归系数(95%CI)(0.31(0.001-0.62))显著高于治疗性低分子肝(0.09(0.05-0.13))。此外，ROC分析显示，CT比、aPTT和anti-Xa检测UFH的曲线下面积分别为0.936(0.849-1.00)、0.851(0.702-1.000)和0.645(0.465-0.826)。结论ROTEM tem /HEPTEM CT比值是指导COVID-19重症监护病房患者抗凝治疗的一个很有前景的工具，但目前缺乏与临床终点的相关性。
{"title":"Applications of rotational thromboelastometry in heparin monitoring in critical COVID-19 disease: Observations in the Maastricht Intensive Care COVID cohort","authors":"Lejan Schultinge , Anne-Marije Hulshof , Danihel van Neerven , Mark M.G. Mulder , Jan-Willem E.M. Sels , Hendrina P.M.G. Hulsewe , Gehardus J.A.J.M. Kuiper , Renske H. Olie , Hugo ten Cate , Iwan C.C. van der Horst , Bas C.T. van Bussel , Yvonne M.C. Henskens","doi":"10.1016/j.tru.2023.100140","DOIUrl":"10.1016/j.tru.2023.100140","url":null,"abstract":"<div><h3>Background</h3><p>Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays.</p></div><div><h3>Objective</h3><p>To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH.</p></div><div><h3>Material and methods</h3><p>A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics.</p></div><div><h3>Results</h3><p>A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3–1.4]) compared to patients treated with LMWH (1.0 [1.0–1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001–0.62)) compared to therapeutic LMWH (0.09 (0.05–0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849–1.00), 0.851(0.702–1.000), and 0.645(0.465–0.826) for the CT ratio, aPTT, and anti-Xa, respectively.</p></div><div><h3>Conclusion</h3><p>The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"12 ","pages":"Article 100140"},"PeriodicalIF":0.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46012957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1016/j.tru.2023.100139
Dionne C.W. Braeken , Roisin Bavalia , Yvonne M.C. Henskens , Hugo ten Cate , Rutger C.C. Hengeveld , Barbara A. Hutten , Saskia Middeldorp , Michiel Coppens , An K. Stroobants
Background
Routine monitoring direct oral anticoagulants (DOAC) is not recommended, yet DOAC levels are frequently measured in clinical practice. Interpretation of levels, especially those outside expected ranges, is challenging. Until now it's unclear which patients are at risk for these levels.
Aim
Identify clinical characteristics of patients with DOAC levels outside expected ranges.
Methods
Patients of 2 Dutch academic medical centers with a DOAC concentration measured between 2012 and 2019 were included. DOAC levels above upper limit peak and below lower limit trough ranges, based on DOAC registration trials, were assigned outside expected range. Differences between patients were evaluated using Chi-square, independent sample-T tests and multivariable logistic regression analysis.
Results
Of 597 patients with DOAC measurement, 108 (18.1%) had levels outside expected ranges. Compared to patients with levels within range, patients with levels above range (n = 64) were older (71.1 vs. 60.6 years), more often had creatinine clearance <50 ml/min (32.8% vs. 13.9%). and used more often interacting (17.2% vs. 6.7%) and/or antiplatelet co-medication (25.0% vs. 13.1%). Patients with levels above (62.5%) and below range (61.4%) more often had atrial fibrillation as DOAC indication versus patients with levels within range (39.1%). Age (OR 1.046 [1.025–1.068]) was associated with levels above range, while dabigatran versus apixaban was associated with levels below range (OR 6.060 [1.836–19.996]).
Conclusion
Particularly older aged patients with additional comorbidity and co-medication had DOAC levels outside expected ranges. Prospective studies are essential to investigate whether identification of patients with levels outside expected ranges is necessary to reduce the risk of clinically relevant adverse events.
{"title":"Clinical characteristics of patients with direct oral anticoagulant (DOAC) levels outside expected ranges: A retrospective chart study","authors":"Dionne C.W. Braeken , Roisin Bavalia , Yvonne M.C. Henskens , Hugo ten Cate , Rutger C.C. Hengeveld , Barbara A. Hutten , Saskia Middeldorp , Michiel Coppens , An K. Stroobants","doi":"10.1016/j.tru.2023.100139","DOIUrl":"10.1016/j.tru.2023.100139","url":null,"abstract":"<div><h3>Background</h3><p>Routine monitoring direct oral anticoagulants (DOAC) is not recommended, yet DOAC levels are frequently measured in clinical practice. Interpretation of levels, especially those outside expected ranges, is challenging. Until now it's unclear which patients are at risk for these levels.</p></div><div><h3>Aim</h3><p>Identify clinical characteristics of patients with DOAC levels outside expected ranges.</p></div><div><h3>Methods</h3><p>Patients of 2 Dutch academic medical centers with a DOAC concentration measured between 2012 and 2019 were included. DOAC levels above upper limit peak and below lower limit trough ranges, based on DOAC registration trials, were assigned outside expected range. Differences between patients were evaluated using Chi-square, independent sample-T tests and multivariable logistic regression analysis.</p></div><div><h3>Results</h3><p>Of 597 patients with DOAC measurement, 108 (18.1%) had levels outside expected ranges. Compared to patients with levels within range, patients with levels above range (n = 64) were older (71.1 vs. 60.6 years), more often had creatinine clearance <50 ml/min (32.8% vs. 13.9%). and used more often interacting (17.2% vs. 6.7%) and/or antiplatelet co-medication (25.0% vs. 13.1%). Patients with levels above (62.5%) and below range (61.4%) more often had atrial fibrillation as DOAC indication versus patients with levels within range (39.1%). Age (OR 1.046 [1.025–1.068]) was associated with levels above range, while dabigatran versus apixaban was associated with levels below range (OR 6.060 [1.836–19.996]).</p></div><div><h3>Conclusion</h3><p>Particularly older aged patients with additional comorbidity and co-medication had DOAC levels outside expected ranges. Prospective studies are essential to investigate whether identification of patients with levels outside expected ranges is necessary to reduce the risk of clinically relevant adverse events.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"11 ","pages":"Article 100139"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45143307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1016/j.tru.2023.100133
Jason Chung , Sajjad Afraz , Federico Germini , Ivan Stevic , Davide Matino , Anthony KC. Chan
Background
Plasma D-Dimer (DD) is a degradation product of cross-linked fibrin and represents the activation of the fibrinolytic and coagulation system. Clinically, DD tests have a high negative prediction value for thrombotic events and can be used to rule-out venous thromboembolism (VTE). The DD cut-off value for VTE in humans is 500 ng/mL; however, the baseline and cut-off values for rats are unknown.
Aims
To systematically evaluate the reported results and methodology of DD tests on rat models.
Methods
A systematic literature search was conducted using MEDLINE, EMBASE and Web of Science to include relevant full-length publications, published abstracts and conference proceedings from Jan-01-2000 to Dec-20-2019 that reported rat DD values. The search strategy used categorical search terms: “rat” AND “D-dimer” OR “fibrin degradation product”. Eligible articles were independently reviewed for strain, age, sex, baseline DD and measurement methodology.
Results
Of the 520 identified records 60 studies were included for qualitative analysis. The three primary rat strains used had a body mass ranging from 160 to 410 g and of both sexes were included in the analysis. There was a significant difference in reported baseline DD that was seen both, within and between rat strains and detection methodologies.
Conclusion
Large discrepancies in reported rat plasma DD values suggest that factors such as species and detection methods can lead to the variation of results and should be considered when designing a rat model that measures DD. We recommend using related negative control models as a baseline DD reference range for each study aiming to measure DD level in rats. Further research is required to establish a standardized reference range for baseline DD levels to help scientists better interpret rat DD test results.
血浆d -二聚体(DD)是交联纤维蛋白的降解产物，代表了纤溶和凝血系统的激活。临床上，DD试验对血栓事件有很高的阴性预测值，可用于排除静脉血栓栓塞(VTE)。人类静脉血栓栓塞的DD临界值为500纳克/毫升;然而，大鼠的基线值和临界值是未知的。目的对已报道的大鼠模型DD试验结果和方法进行系统评价。方法采用MEDLINE、EMBASE和Web of Science进行系统文献检索，检索2000年1月1日至2019年12月20日期间报道大鼠DD值的相关全文出版物、已发表摘要和会议论文集。搜索策略使用分类搜索词:“大鼠”和“d -二聚体”或“纤维蛋白降解产物”。对符合条件的文章进行独立审查，包括菌株、年龄、性别、基线DD和测量方法。结果在520份确定的记录中，有60份研究被纳入定性分析。所使用的三种主要大鼠品系的体重在160至410克之间，雌雄都包括在分析中。报告的基线DD在大鼠品系内和品系之间以及检测方法上均有显著差异。结论报告的大鼠血浆DD值存在较大差异，表明物种和检测方法等因素可能导致结果的差异，在设计测量DD的大鼠模型时应考虑这些因素。我们建议在每项旨在测量大鼠DD水平的研究中使用相关的阴性对照模型作为基线DD参考范围。为了帮助科学家更好地解释大鼠DD测试结果，需要进一步的研究来建立一个标准化的基线DD水平参考范围。
{"title":"Heterogeneity in the reported values and methodologies for detecting plasma D-Dimer in rat models: A systematic review","authors":"Jason Chung , Sajjad Afraz , Federico Germini , Ivan Stevic , Davide Matino , Anthony KC. Chan","doi":"10.1016/j.tru.2023.100133","DOIUrl":"10.1016/j.tru.2023.100133","url":null,"abstract":"<div><h3>Background</h3><p>Plasma D-Dimer (DD) is a degradation product of cross-linked fibrin and represents the activation of the fibrinolytic and coagulation system. Clinically, DD tests have a high negative prediction value for thrombotic events and can be used to rule-out venous thromboembolism (VTE). The DD cut-off value for VTE in humans is 500 ng/mL; however, the baseline and cut-off values for rats are unknown.</p></div><div><h3>Aims</h3><p>To systematically evaluate the reported results and methodology of DD tests on rat models.</p></div><div><h3>Methods</h3><p>A systematic literature search was conducted using MEDLINE, EMBASE and Web of Science to include relevant full-length publications, published abstracts and conference proceedings from Jan-01-2000 to Dec-20-2019 that reported rat DD values. The search strategy used categorical search terms: “rat” AND “D-dimer” OR “fibrin degradation product”. Eligible articles were independently reviewed for strain, age, sex, baseline DD and measurement methodology.</p></div><div><h3>Results</h3><p>Of the 520 identified records 60 studies were included for qualitative analysis. The three primary rat strains used had a body mass ranging from 160 to 410 g and of both sexes were included in the analysis. There was a significant difference in reported baseline DD that was seen both, within and between rat strains and detection methodologies.</p></div><div><h3>Conclusion</h3><p>Large discrepancies in reported rat plasma DD values suggest that factors such as species and detection methods can lead to the variation of results and should be considered when designing a rat model that measures DD. We recommend using related negative control models as a baseline DD reference range for each study aiming to measure DD level in rats. Further research is required to establish a standardized reference range for baseline DD levels to help scientists better interpret rat DD test results.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"11 ","pages":"Article 100133"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43178073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-05-01DOI: 10.1016/j.tru.2023.100138
Daniel G. Whitney , Elizabeth J. Lucas , Mary Schmidt , Heidi Haapala , Garey Noritz
Introduction
The risk of venous thromboembolism (VTE) for individuals with cerebral palsy (CP) is understudied. The objectives were to characterize the incidence of VTE by age and sex for individuals with CP compared with those without CP at the population- and clinical-levels.
Materials and methods
This retrospective cohort study used commercial claims from 1 January, 2011 to 31 December, 2017 from individuals of any age with and without CP. Sex-stratified incidence rate (IR) per 1000 person-years and IR ratio (IRR) of VTE were assessed across the lifespan up to 2-years of follow-up. The IR, IRR, and hazard ratio (HR using Cox regression) of VTE were assessed within 30-days following placement of a central venous catheter (CVC) (in one analysis) and orthopedic surgery (in another analysis).
Results
The 2-year IR of VTE for the full cohorts with (n = 20,486) and without (n = 22,161,726) CP was 19.1 and 9.7 for females (IRR = 1.97; 95%CI = 1.77–2.19) and 19.0 and 8.6 for males (IRR = 2.22; 95% CI = 2.01–2.45). The 30-day HR of VTE post-CVC (CP n = 1963; non-CP n = 558,150) was higher for adult males compared with those without CP (HR = 1.25 by 40 years to 1.80 by 80 years), but was not higher in pediatric males or females of any age compared with those without CP. The 30-day HR of VTE post-surgery (CP: n = 2634; non-CP: n = 1,066,136) was higher for pediatric patients and young adults compared with those without CP (HR = 2.58 to 2.79) There was no signficant difference between the groups among the older age groups.
Conclusions
The risk of VTE was elevated for individuals with CP across the lifespan, and some subgroups of CP had a greater 30-day risk of VTE following CVC placement and orthopedic surgery.
脑瘫(CP)患者发生静脉血栓栓塞(VTE)的风险尚不清楚。目的是在人群和临床水平上，以年龄和性别区分患有CP的个体与没有CP的个体的静脉血栓栓塞发生率。材料和方法本回顾性队列研究使用了2011年1月1日至2017年12月31日期间任何年龄的有或没有CP的个体的商业声明。在长达2年的随访期间，评估了VTE的性别分层发病率(每1000人年IR)和IR比率(IRR)。在放置中心静脉导管(CVC)(一项分析)和骨科手术(另一项分析)后30天内评估VTE的IR、IRR和风险比(使用Cox回归的HR)。结果在有(n = 20,486)和没有(n = 22,161,726) CP的全队列中，VTE的2年IR为19.1，女性为9.7 (IRR = 1.97;95%CI = 1.77-2.19)，男性分别为19.0和8.6 (IRR = 2.22;95% ci = 2.01-2.45)。VTE术后30天HR (CP n = 1963;非CP n = 558,150)在成年男性中高于无CP者(HR = 1.25 by 40至1.80 by 80)，但在任何年龄的儿童男性或女性中均不高于无CP者。非CP: n = 1,066,136)在儿科患者和青壮年患者中高于非CP患者(HR = 2.58 ~ 2.79)，在老年组中组间无显著差异。结论:CP患者在整个生命周期中发生VTE的风险升高，某些CP亚组在CVC放置和骨科手术后30天发生VTE的风险更高。
{"title":"Risk of venous thromboembolism across the lifespan for individuals with cerebral palsy: A retrospective cohort study","authors":"Daniel G. Whitney , Elizabeth J. Lucas , Mary Schmidt , Heidi Haapala , Garey Noritz","doi":"10.1016/j.tru.2023.100138","DOIUrl":"10.1016/j.tru.2023.100138","url":null,"abstract":"<div><h3>Introduction</h3><p>The risk of venous thromboembolism (VTE) for individuals with cerebral palsy (CP) is understudied. The objectives were to characterize the incidence of VTE by age and sex for individuals with CP compared with those without CP at the population- and clinical-levels.</p></div><div><h3>Materials and methods</h3><p>This retrospective cohort study used commercial claims from 1 January, 2011 to 31 December, 2017 from individuals of any age with and without CP. Sex-stratified incidence rate (IR) per 1000 person-years and IR ratio (IRR) of VTE were assessed across the lifespan up to 2-years of follow-up. The IR, IRR, and hazard ratio (HR using Cox regression) of VTE were assessed within 30-days following placement of a central venous catheter (CVC) (in one analysis) and orthopedic surgery (in another analysis).</p></div><div><h3>Results</h3><p>The 2-year IR of VTE for the full cohorts with (n = 20,486) and without (n = 22,161,726) CP was 19.1 and 9.7 for females (IRR = 1.97; 95%CI = 1.77–2.19) and 19.0 and 8.6 for males (IRR = 2.22; 95% CI = 2.01–2.45). The 30-day HR of VTE post-CVC (CP n = 1963; non-CP n = 558,150) was higher for adult males compared with those without CP (HR = 1.25 by 40 years to 1.80 by 80 years), but was not higher in pediatric males or females of any age compared with those without CP. The 30-day HR of VTE post-surgery (CP: n = 2634; non-CP: n = 1,066,136) was higher for pediatric patients and young adults compared with those without CP (HR = 2.58 to 2.79) There was no signficant difference between the groups among the older age groups.</p></div><div><h3>Conclusions</h3><p>The risk of VTE was elevated for individuals with CP across the lifespan, and some subgroups of CP had a greater 30-day risk of VTE following CVC placement and orthopedic surgery.</p></div>","PeriodicalId":34401,"journal":{"name":"Thrombosis Update","volume":"11 ","pages":"Article 100138"},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47830637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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