Journal of Thrombosis and Haemostasis最新文献

筛选
英文 中文
Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A. 比较 A 型血友病女性患者的单阶段显色测定结果以及与出血表型和遗传变异的差异。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-11-12 DOI: 10.1016/j.jtha.2024.10.030
Lakshmi Srivaths, Joanna Larson, Sepideh Saroukhani, Mohammed Said, Deborah Brown, Nidra Rodriguez, Neethu Menon, Miguel Escobar
{"title":"Comparing one stage, chromogenic assay results and discrepancies with bleeding phenotype and genetic variants in females with hemophilia A.","authors":"Lakshmi Srivaths, Joanna Larson, Sepideh Saroukhani, Mohammed Said, Deborah Brown, Nidra Rodriguez, Neethu Menon, Miguel Escobar","doi":"10.1016/j.jtha.2024.10.030","DOIUrl":"10.1016/j.jtha.2024.10.030","url":null,"abstract":"<p><strong>Background: </strong>Increasing evidence in females with hemophilia A has shown significant bleeding symptoms. Accurate factor (F) VIII activity (FVIII:C) measurement is essential to assign correct diagnosis and severity. Assay discrepancies reported in male patients with hemophilia A are not well studied in females.</p><p><strong>Objectives: </strong>Our research sought to assess the association of FVIII:C levels by one-stage versus chromogenic assays and the assay discrepancy with bleeding phenotype and genetic mutation in females with hemophilia A.</p><p><strong>Methods: </strong>Data from 64 females with hemophilia A from our center were reviewed with center's institutional review board approval. Descriptive statistics, chi-squared, Fisher's exact, and Bland-Altman plot analysis were applied.</p><p><strong>Results: </strong>Abnormal International Society on Thrombosis and Haemostasis bleeding assessment tool score was seen in 52% (FVIII:C <40 IU/dL: 72%/73%; FVIII:C ≥40 IU/dL: 41%/45%; by one-stage and chromogenic assays, respectively), more often in adults and postmenarchal patients. Assay discrepancies were present, direct more often than inverse. Based on one assay result only, 11 (17%) patients would have been incorrectly diagnosed and 1 (1.5%) patient would have been assigned incorrect hemophilia severity. No associations of genetic variants with FVIII:C levels and bleeding phenotype were found.</p><p><strong>Conclusion: </strong>Our study emphasizes the importance of evaluating female patients with hemophilia A for bleeding phenotype. Our study is the first to document prevalence of assay discrepancies exclusively in females with hemophilia A, which can lead to inaccurate diagnosis and severity assignment. Future larger, multicenter studies are needed to validate our findings, to help develop recommendations regarding the appropriate use of assays for accurate diagnosis and to further elucidate the association of genetic variants with bleeding phenotype and assay discrepancies.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The dynamic range of immunoassays for heparin-induced thrombocytopenia. 肝素诱导的血小板减少症免疫测定的动态范围。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-11-12 DOI: 10.1016/j.jtha.2024.10.026
Henning Nilius, Samra Naas, Jan-Dirk Studt, Dimitrios A Tsakiris, Andreas Greinacher, Adriana Mendez, Adrian Schmidt, Walter A Wuillemin, Bernhard Gerber, Prakash Vishnu, Lukas Graf, Johanna A Kremer Hovinga, Tamam Bakchoul, Christos Nakas, Michael Nagler
{"title":"The dynamic range of immunoassays for heparin-induced thrombocytopenia.","authors":"Henning Nilius, Samra Naas, Jan-Dirk Studt, Dimitrios A Tsakiris, Andreas Greinacher, Adriana Mendez, Adrian Schmidt, Walter A Wuillemin, Bernhard Gerber, Prakash Vishnu, Lukas Graf, Johanna A Kremer Hovinga, Tamam Bakchoul, Christos Nakas, Michael Nagler","doi":"10.1016/j.jtha.2024.10.026","DOIUrl":"10.1016/j.jtha.2024.10.026","url":null,"abstract":"<p><strong>Background: </strong>Following the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted dichotomously, with test results categorized as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear.</p><p><strong>Objectives: </strong>We utilized data from the prospective towards precise and rapid diagnosis of heparin-induced thrombocytopenia study, comprising 1393 consecutive patients with suspected HIT, to assess the diagnostic significance of 2 heparin/platelet factor 4 immunoassay test results across their respective dynamic ranges: HemoSil Acustar HIT IgG (chemiluminescence immunoassay [CLIA]) and Lifecodes PF4 immunoglobulin G (enzyme-linked immunosorbent assay [ELISA]).</p><p><strong>Methods: </strong>HIT diagnosis was determined by a washed platelet heparin-induced platelet activation assay. For each measurement point in the dataset, we computed likelihood ratios (LRs), sensitivities, and specificities. To provide posttest probabilities for individual test results, we calculated interval-specific LRs and integrated them into a web-based calculator.</p><p><strong>Results: </strong>The prevalence of HIT was 8.5% (n = 119). An LR of ≥10 was first achieved at 0.3% of the dynamic range (0.4 U/mL; CLIA) and then at 16% (0.64 optical density; ELISA). An LR of ≥100 was present at 9.4% (12 U/mL; CLIA) and 75.0% (3.0 optical density; ELISA). The slope of the linear regression line (LR ∼ dynamic range) was 9.5 (CLIA) and 0.9 (ELISA).</p><p><strong>Conclusion: </strong>Despite both immunoassays showing an association between results and diagnostic significance, the strength of the association varies by assay. CLIA has a larger increase per measurement unit. Posttest probabilities for individual patients can be estimated using a web-based calculator: https://pcd-research.shinyapps.io/BayesianCalculator/.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The severe von Willebrand disease variant p.M771V leads to impaired anterograde trafficking of von Willebrand factor in patient-derived and base-edited endothelial colony-forming cells. 严重的von Willebrand病变体p.M771V导致患者来源的和碱基编辑的ECFCs中Von Willebrand因子的逆向运输受损。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-11-06 DOI: 10.1016/j.jtha.2024.10.023
Isabel Bär, Alastair Barraclough, Petra E Bürgisser, Calvin van Kwawegen, Karin Fijnvandraat, Jeroen C J Eikenboom, Frank W G Leebeek, Jan Voorberg, Ruben Bierings
{"title":"The severe von Willebrand disease variant p.M771V leads to impaired anterograde trafficking of von Willebrand factor in patient-derived and base-edited endothelial colony-forming cells.","authors":"Isabel Bär, Alastair Barraclough, Petra E Bürgisser, Calvin van Kwawegen, Karin Fijnvandraat, Jeroen C J Eikenboom, Frank W G Leebeek, Jan Voorberg, Ruben Bierings","doi":"10.1016/j.jtha.2024.10.023","DOIUrl":"10.1016/j.jtha.2024.10.023","url":null,"abstract":"<p><strong>Background: </strong>von Willebrand disease (VWD) is the most common inherited bleeding disorder caused by quantitative or qualitative defects in von Willebrand factor (VWF). The p.M771V VWF variant leads to a severe bleeding phenotype in homozygous patients. However, the exact molecular mechanism remains unclear, which prevents personalized treatment of those VWD patients.</p><p><strong>Objectives: </strong>This study aimed to characterize the underlying molecular mechanisms of the p.M771V variant in multiple representative ex vivo cell models.</p><p><strong>Methods: </strong>Endothelial colony-forming cells (ECFCs) were isolated from venous blood of VWD patients from the Willebrand in the Netherlands cohort carrying homozygous and heterozygous p.M771V VWF variants. The p.M771V variant was also introduced in cord blood-derived ECFCs (CB-ECFCs) through adenine base editing and was overexpressed in HEK293 cells. Biosynthesis, storage, and secretion of VWF was studied using biochemical methods and confocal microscopy.</p><p><strong>Results: </strong>Two unrelated homozygous p.M771V patients presented with very low VWF activity and antigen levels in plasma. Patient ECFCs showed impaired uncleaved VWF processing into mature VWF, with secreted VWF being severely reduced when compared to ECFCs of healthy donors. Multimer analysis of p.M771V ECFCs showed a deficiency of high molecular weight VWF multimers. Immunofluorescent staining revealed VWF retention in the endoplasmic reticulum; this was confirmed in various populations of base-edited CB-ECFCs harboring the p.M771V variant.</p><p><strong>Conclusion: </strong>The severe endothelial phenotype observed in patient-derived p.M771V ECFCs, HEK293 cells, and an original base-edited CB-ECFC modeling system show that endoplasmic reticulum retention of VWF and failure to undergo subsequent proteolytic processing underpins the severe bleeding phenotype of patients with homozygous variants at M771.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. 实验室检测和解读抗磷脂抗体以诊断抗磷脂综合征的最新进展:国际血栓与止血学会科学与标准化委员会(ISTH-SSC)狼疮抗凝物/抗磷脂抗体小组委员会的指南。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-11-05 DOI: 10.1016/j.jtha.2024.10.022
Katrien M J Devreese, Maria Laura Bertolaccini, D Ware Branch, Bas de Laat, Doruk Erkan, Emmanuel J Favaloro, Vittorio Pengo, Thomas L Ortel, Denis Wahl, Hannah Cohen
{"title":"An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: guidance from the ISTH-SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.","authors":"Katrien M J Devreese, Maria Laura Bertolaccini, D Ware Branch, Bas de Laat, Doruk Erkan, Emmanuel J Favaloro, Vittorio Pengo, Thomas L Ortel, Denis Wahl, Hannah Cohen","doi":"10.1016/j.jtha.2024.10.022","DOIUrl":"10.1016/j.jtha.2024.10.022","url":null,"abstract":"<p><p>Antiphospholipid syndrome (APS) diagnosis is dependent on the accurate detection and interpretation of antiphospholipid antibodies (aPL). Lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis. In the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, the type of laboratory parameters remain essentially unchanged compared with the updated Sapporo classification criteria, and aCL and aβ2GPI measurement are still restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively, and a cutoff calculated by the 99th percentile has been abandoned. We must differentiate between classification criteria and assessment of aPLs in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader, meant to diagnose each APS patient to optimize their management. Nowadays, there is increasing use of measurement of aPLs by methods other than ELISAs , the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes immunoglobulin (Ig)M and IgA, and the role of other aPLs, such as antiphosphatidylserine (aPS)/prothrombin (PT) antibodies. Patients diagnosed with the disease may or may not fulfill the classification criteria, and inappropriate use of classification criteria may lead to mis(under)diagnosis. The aim of this guidance, based on literature and expert opinion, is to provide guidance recommendations for laboratory workers and clinicians on routine diagnostic assessment of patients with suspected APS.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Validating International Classification of Diseases Code 10th Revision algorithms for accurate identification of pulmonary embolism. 验证国际疾病分类代码 (ICD) 第 10 次修订版算法,以准确识别肺栓塞。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-11-04 DOI: 10.1016/j.jtha.2024.10.013
Behnood Bikdeli, Candrika D Khairani, Antoine Bejjani, Ying-Chih Lo, Shiwani Mahajan, César Caraballo, Jose Victor Jimenez, Darsiya Krishnathasan, Mehrdad Zarghami, Sina Rashedi, David Jimenez, Stefano Barco, Eric A Secemsky, Frederikus A Klok, Andetta R Hunsaker, Ayaz Aghayev, Alfonso Muriel, Mohamad A Hussain, Abena Appah-Sampong, Yuan Lu, Zhenqiu Lin, Hamid Mojibian, Sanjay Aneja, Rohan Khera, Stavros Konstantinides, Samuel Z Goldhaber, Liqin Wang, Li Zhou, Manuel Monreal, Gregory Piazza, Harlan M Krumholz
{"title":"Validating International Classification of Diseases Code 10th Revision algorithms for accurate identification of pulmonary embolism.","authors":"Behnood Bikdeli, Candrika D Khairani, Antoine Bejjani, Ying-Chih Lo, Shiwani Mahajan, César Caraballo, Jose Victor Jimenez, Darsiya Krishnathasan, Mehrdad Zarghami, Sina Rashedi, David Jimenez, Stefano Barco, Eric A Secemsky, Frederikus A Klok, Andetta R Hunsaker, Ayaz Aghayev, Alfonso Muriel, Mohamad A Hussain, Abena Appah-Sampong, Yuan Lu, Zhenqiu Lin, Hamid Mojibian, Sanjay Aneja, Rohan Khera, Stavros Konstantinides, Samuel Z Goldhaber, Liqin Wang, Li Zhou, Manuel Monreal, Gregory Piazza, Harlan M Krumholz","doi":"10.1016/j.jtha.2024.10.013","DOIUrl":"10.1016/j.jtha.2024.10.013","url":null,"abstract":"<p><strong>Background: </strong>Many research investigations for pulmonary embolism (PE) rely on the International Classification of Diseases 10th Revision (ICD-10) codes for analyses of electronic databases. The validity of ICD-10 codes in identifying PE remains uncertain.</p><p><strong>Objectives: </strong>The objective of this study was to validate an algorithm to efficiently identify pulmonary embolism using ICD-10 codes.</p><p><strong>Methods: </strong>Using a prespecified protocol, patients in the Mass General-Brigham hospitals (2016-2021) with ICD-10 principal discharge codes for PE, those with secondary codes for PE, and those without PE codes were identified (n = 578 from each group). Weighting was applied to represent each group proportionate to their true prevalence. The accuracy of ICD-10 codes for identifying PE was compared with adjudication by independent physicians. The F1 score, which incorporates sensitivity and positive predictive value (PPV), was assessed. Subset validation was performed at Yale-New Haven Health System.</p><p><strong>Results: </strong>A total of 1712 patients were included (age: 60.6 years; 52.3% female). ICD-10 PE codes in the principal discharge position had sensitivity and PPV of 58.3% and 92.1%, respectively. Adding secondary discharge codes to the principal discharge codes improved the sensitivity to 83.2%, but the PPV was reduced to 79.1%. Using a combination of ICD-10 PE principal discharge codes or secondary codes plus imaging codes for PE led to sensitivity and PPV of 81.6% and 84.7%, respectively, and the highest F1 score (83.1%; P < .001 compared with other methods). Validation yielded largely similar results.</p><p><strong>Conclusion: </strong>Although the principal discharge codes for PE show excellent PPV, they miss 40% of acute PEs. A combination of principal discharge codes and secondary codes plus PE imaging codes led to improved sensitivity without severe reduction in PPV.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
High risk of long-term recurrence after a first episode of venous thromboembolism during pregnancy or postpartum: the REcurrence after a PrEgnAncy related Thrombosis (REPEAT) Study. 孕期或产后首次发生静脉血栓栓塞后长期复发的高风险:与血栓形成有关的孕期或产后复发(REPEAT)研究。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-10-31 DOI: 10.1016/j.jtha.2024.09.039
Manal Ibrahim-Kosta, Sarah El Harake, Barbara Leclercq, Céline De Mari, Jean-François Secondi, Emilie Paoletti, Pierre Suchon, Yasmine Benredouane, Dominique Brunet, Marie-Christine Barthet, Maria Bruzelius, Gaëlle Munsch, David-Alexandre Trégouët, Pierre-Emmanuel Morange, Louisa Goumidi, Gabrielle Sarlon-Bartoli
{"title":"High risk of long-term recurrence after a first episode of venous thromboembolism during pregnancy or postpartum: the REcurrence after a PrEgnAncy related Thrombosis (REPEAT) Study.","authors":"Manal Ibrahim-Kosta, Sarah El Harake, Barbara Leclercq, Céline De Mari, Jean-François Secondi, Emilie Paoletti, Pierre Suchon, Yasmine Benredouane, Dominique Brunet, Marie-Christine Barthet, Maria Bruzelius, Gaëlle Munsch, David-Alexandre Trégouët, Pierre-Emmanuel Morange, Louisa Goumidi, Gabrielle Sarlon-Bartoli","doi":"10.1016/j.jtha.2024.09.039","DOIUrl":"10.1016/j.jtha.2024.09.039","url":null,"abstract":"<p><strong>Background: </strong>The long-term recurrence risk after a pregnancy-associated venous thromboembolism (VTE) is sparsely assessed.</p><p><strong>Objectives: </strong>To determine the rate of recurrence after a pregnancy-associated VTE and identify associated risk factors.</p><p><strong>Methods: </strong>Five hundred eighty-seven women with a history of first VTE occurring during pregnancy or up to 3 months after delivery were referred to La Timone Hospital, Marseille, France. Women were consecutively included between 2000 and 2015. VTE characteristics and biological parameters were collected upon inclusion. During the 2016-2019 period, patients were recontacted to gather information on postinclusion VTE. A weighted Cox model, adapted to the study's ambispective design, was used to analyze pre- and postinclusion VTE recurrences.</p><p><strong>Results: </strong>After quality controls, 583 women were analyzed. The incidence of recurrent VTE was 2.4% person-years. The cumulative risk of VTE recurrence was 38% (n = 221), with a median follow-up of 31 years (95% CI: 27-35); 6%, 13%, 17%, and 30% at 2, 5, 10, and 30 years respectively. Pulmonary embolism at first event was associated with a 2-fold increased risk of pulmonary embolism at recurrence compared with isolated deep venous thrombosis (DVT, hazard ratio [HR]: 2.63; 95% CI: 1.44-4.82). Risk factors significantly associated with recurrence were interrupted pregnancies (HR: 1.85; 95% CI: 1.18-2.90), lower limb DVT (HR: 2.95; 95% CI: 1.16-7.49), and AB blood group (HR: 1.71; 95% CI: 1.06-2.77).</p><p><strong>Conclusion: </strong>Although the recurrence risk is low within the first 10 years after a pregnancy-associated VTE, one-third of patients experienced a new event over a 30-year period. Interrupted pregnancies, lower limb DVT, and AB blood group were associated with higher risk of recurrence.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study. 癌症患者静脉血栓栓塞临床风险评估评分的验证:一项基于人群的队列研究。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-10-29 DOI: 10.1016/j.jtha.2024.10.021
Vincent Lanting, Emese Vágó, Erzsébet Horváth-Puhó, Frits Mulder, Marcello Di Nisio, Pieter W Kamphuisen, Lars Pedersen, Nick van Es, Henrik T Sørensen
{"title":"Validation of clinical risk assessment scores for venous thromboembolism in patients with cancer: a population-based cohort study.","authors":"Vincent Lanting, Emese Vágó, Erzsébet Horváth-Puhó, Frits Mulder, Marcello Di Nisio, Pieter W Kamphuisen, Lars Pedersen, Nick van Es, Henrik T Sørensen","doi":"10.1016/j.jtha.2024.10.021","DOIUrl":"10.1016/j.jtha.2024.10.021","url":null,"abstract":"<p><strong>Background: </strong>Guidelines recommend using risk assessment tools to identify ambulatory patients with cancer at high risk of venous thromboembolism (VTE).</p><p><strong>Objectives: </strong>We aimed to validate a new cancer-associated thrombosis (CAT) risk score in a population-based healthcare setting.</p><p><strong>Methods: </strong>We used healthcare registry data and electronic medical records from the Central Denmark Region to calculate the new CAT risk score and the guideline-recommended Khorana score in patients with a first-time cancer diagnosis who initiated systemic cancer therapy. Patients were followed for 6 months after initiation of therapy. The outcome was any VTE identified through hospital discharge diagnoses. Discrimination was assessed using C statistics.</p><p><strong>Results: </strong>We included 12 471 patients from 2012 to 2020. Of these, 416 (3.3%) developed VTE. The C statistic was 0.71 (95% CI, 0.68-0.74) for the new CAT score and 0.66 (95% CI, 0.63-0.70) for the Khorana score. The 6-month cumulative VTE incidence was 5.0% in 6175 patients classified as high risk by the new CAT score compared with 1.7% in 6296 patients classified as low risk. The 6-month cumulative VTE incidence was 5.2% in 4263 patients classified as high risk by the Khorana score compared with 2.4% in 8208 patients classified as low risk.</p><p><strong>Conclusion: </strong>The new CAT score had a discriminatory ability similar to that reported in the derivation study. The C statistic was numerically higher than that of the Khorana score. Our findings support the implementation of the new CAT score to identify ambulatory patients with cancer who are at high risk of VTE.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Déjà vu all over again: a recurrent flaw in anticoagulant study design. 似曾相识:抗凝剂研究设计中反复出现的缺陷。
IF 8.3 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-10-28 DOI: 10.1016/j.jtha.2024.10.019
Bethany Samuelson Bannow, Alison Edelman, Marc Carrier
{"title":"Déjà vu all over again: a recurrent flaw in anticoagulant study design.","authors":"Bethany Samuelson Bannow, Alison Edelman, Marc Carrier","doi":"10.1016/j.jtha.2024.10.019","DOIUrl":"10.1016/j.jtha.2024.10.019","url":null,"abstract":"<p><p>The availability of direct oral anticoagulants rapidly changed the landscape of anticoagulation between 2010 and the present. Randomized controlled trials demonstrating efficacy with similar or superior safety compared with warfarin led to the widespread use of direct oral anticoagulants in male and female patients of all ages. Years later, postmarketing data demonstrated a markedly increased rate of heavy menstrual bleeding (HMB) with rivaroxaban that had gone undetected in registry trials. Factor (F)XI inhibitors are currently being investigated as another alternative to available anticoagulation agents. While generally mild, the phenotype of inherited FXI deficiency includes bleeding in tissues with enhanced fibrinolysis, including HMB. Thus, we aimed to perform a systematic review of published studies on FXI inhibitors in order to estimate rates of HMB. However, we found that few studies included menstruating individuals, and even fewer specifically reported on uterine bleeding, highlighting once again a flaw in our approach to conducting trials of new anticoagulants.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study. 肥厚性滑膜血友病患者的强化 FVIII 替代治疗:随机研究。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-10-28 DOI: 10.1016/j.jtha.2024.10.018
Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli
{"title":"Intensive FVIII replacement in hemophilia patients with hypertrophic synovium: a randomized study.","authors":"Matteo Nicola Dario Di Minno, Ilenia Lorenza Calcaterra, Erminia Baldacci, Renato Marino, Federica Valeri, Rita Carlotta Santoro, Gianluigi Pasta, Carlo Martinoli","doi":"10.1016/j.jtha.2024.10.018","DOIUrl":"10.1016/j.jtha.2024.10.018","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic synovium (HS) is a marker of disease activity in persons with hemophilia (PwH). Although some recommendations suggest intensifying prophylaxis in PwH with HS, no validated schedules are available.</p><p><strong>Objectives: </strong>We explored the efficacy of intensive factor VIII (FVIII) replacement treatment in PwH with HS.</p><p><strong>Methods: </strong>In a randomized, open-label study, PwH with HS were randomized to receive pharmacokinetics-driven prophylaxis targeting a FVIII trough level of 8% to 12% (intensive treatment arm [ITA]) or 3% to 5% (standard treatment arm [STA]). The primary outcome was HS reduction/resolution in the 2 treatment arms.</p><p><strong>Results: </strong>A total of 39 PwH were randomized to ITA and 36 to STA. During the study, we found a lower annual bleeding rate and a higher rate of annual bleeding rate zero in the ITA than in the STA. HS reduction/resolution was reported in 35.9% of cases in the ITA and 8.4% in the STA. In detail, in the ITA ,10.3% achieved HS reduction and 25.6% complete HS resolution, as compared to 5.6% and 2.8% in the STA. Cox regression showed that ITA was associated with HS reduction/resolution (hazard ratio: 4.75; 95% CI: 1.36-16.57; P = .014) and HS complete resolution (hazard ratio: 10.79; 95% CI: 1.38-84.45; P = .023). The analysis of the 127 joints with HS (54 elbows, 41 knees, and 32 ankles) consistently confirmed similar results.</p><p><strong>Conclusion: </strong>In this randomized study, we found a ∼5-fold higher rate of HS reduction/resolution and a ∼10-fold higher rate of HS resolution in the ITA than in the STA.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Persistent splenic-derived IgMs preferentially recognize factor VIII A2 and C2 domain epitopes but do not alter antibody production. 持续存在的脾脏衍生 IgM 可优先识别因子 VIIIA2 和 C2 结构域表位,但不会改变抗体的产生。
IF 5.5 2区 医学
Journal of Thrombosis and Haemostasis Pub Date : 2024-10-28 DOI: 10.1016/j.jtha.2024.10.017
Elizabeth S York, Benjamin D Dratch, Jasmine Ito, Samantha M Horwitz, Sahand Emamian, Joseph A Ambarian, Surinder Gill, Jayre Jones, Satheesh Chonat, Pete Lollar, Shannon L Meeks, Katherine M Davis, Glaivy Batsuli
{"title":"Persistent splenic-derived IgMs preferentially recognize factor VIII A2 and C2 domain epitopes but do not alter antibody production.","authors":"Elizabeth S York, Benjamin D Dratch, Jasmine Ito, Samantha M Horwitz, Sahand Emamian, Joseph A Ambarian, Surinder Gill, Jayre Jones, Satheesh Chonat, Pete Lollar, Shannon L Meeks, Katherine M Davis, Glaivy Batsuli","doi":"10.1016/j.jtha.2024.10.017","DOIUrl":"10.1016/j.jtha.2024.10.017","url":null,"abstract":"<p><strong>Background: </strong>The most significant treatment complication for patients with hemophilia A is the development of neutralizing immunoglobins (Igs) G, termed inhibitors, against factor VIII (FVIII), which prevent FVIII replacement therapy. Low titers of FVIII-specific IgMs have been identified in hemophilia A patients with and without inhibitors, as well as in healthy individuals. However, the duration and influence of IgMs on the immune response to FVIII remains unclear.</p><p><strong>Objectives: </strong>To characterize the binding interactions of persistently secreted FVIII-specific IgMs in hemophilia A mice and assess their effect on IgG antibody development.</p><p><strong>Methods: </strong>Splenic-derived monoclonal antibodies (mAbs) from immunized FVIII knockout mice were isolated and purified using hybridoma technology. Binding interactions were assessed utilizing a novel fluid-phase enzyme-linked immunosorbent assay and computational modeling with High Ambiguity-Driven protein-protein DOCKing to account for weak IgM binding.</p><p><strong>Results: </strong>Sixteen porcine cross-reactive and noninhibitory FVIII-specific IgM mAbs were identified. RNA sequencing of FVIII-specific IgMs revealed 13 unique variable, diversity, and joining (VDJ)/variable and joining (VJ) sequences indicating derivation from 13 unique B cell clones. The IgMs demonstrated polyclonal and polyreactive binding to FVIII in vitro and in silico. Molecular docking studies with reconstructed IgM variable, diversity, and joining/variable and joining regions identified frequent IgM interactions with amino acid residues K376, T381, K437, R2215, or K2249 within the FVIII A2 and C2 domains. Injections of individual IgMs prior to FVIII exposure and co-injection of FVIII/IgM immune complexes did not affect de novo FVIII antibody production.</p><p><strong>Conclusion: </strong>Persistent FVIII-specific IgMs are polyclonal but preferentially bind the A2 and C2 domains. FVIII/IgM immune complex formation does not significantly alter inhibitor development.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信