Pub Date : 2024-11-20eCollection Date: 2024-11-01DOI: 10.1016/j.rpth.2024.102630
Khristian S Burke, Xiaowen Kong, Brian Haymart, Debbie DeCamillo, Mona Ali, Geoff Barnes, Scott Kaatz
{"title":"Comparing rates of clinically relevant epistaxis in patients taking warfarin versus direct oral anticoagulants.","authors":"Khristian S Burke, Xiaowen Kong, Brian Haymart, Debbie DeCamillo, Mona Ali, Geoff Barnes, Scott Kaatz","doi":"10.1016/j.rpth.2024.102630","DOIUrl":"https://doi.org/10.1016/j.rpth.2024.102630","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"102630"},"PeriodicalIF":3.4,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932579","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 : 2024-11-15eCollection Date: 2025-01-01DOI: 10.1016/j.rpth.2024.102628
Richard J Buka
Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.
{"title":"Andexanet alfa: trials just leave us with more questions.","authors":"Richard J Buka","doi":"10.1016/j.rpth.2024.102628","DOIUrl":"https://doi.org/10.1016/j.rpth.2024.102628","url":null,"abstract":"<p><p>Andexanet Alfa in Acute Intracranial Hemorrhage in Patients Receiving an Oral Factor Xa Inhibitor (ANNEXA-I), the first ever randomized controlled trial of a reversal agent for direct oral anticoagulants, was published in 2024. The trial, which randomized patients with intracranial hemorrhage to andexanet alfa or usual care, was mandated by the United States Food and Drug Administration as part of its conditional approval in 2018. This approval was originally based on the single-arm trial, The Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of Factor Xa Inhibitors (ANNEXA-4). ANNEXA-I was stopped early for benefit and showed a reduction in the number of patients with significant hematoma expansion. However, the study was not powered for clinical endpoints such as disability or death and showed no difference in these outcomes. It did, however, show an increased risk of thrombosis, predominantly stroke with andexanet alfa. In this perspective, I reflect on some of the key criticisms of the trial and the implications for its interpretation.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"9 1","pages":"102628"},"PeriodicalIF":3.4,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143047731","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102612
Stefan F. van Wonderen , Floor L.F. van Baarle , Anita M. Tuip-de Boer , Chantal A. Polet , Robin van Bruggen , Christie Vermeulen , Thomas R.L. Klei , Chi M. Hau , Rienk Nieuwland , Cornelis van ’t Veer , Anna L. Peters , Sanne de Bruin , Alexander P.J. Vlaar , Bart J. Biemond , Marcella C.A. Müller
Background
Platelet increment is reportedly lower for maximum stored platelet concentrates (PCs) and during pyrexia, and in vitro function differs between fresh and stored PCs. However, little is known about the function of fresh and stored platelets during inflammation.
Objectives
The aim was to study differences in hemostatic function after transfusion of fresh or stored PCs in a human model of experimental endotoxemia.
Methods
Thirty-six healthy male subjects received either 2 ng/kg lipopolysaccharide (LPS) or a control (physiological saline 0.9%) and were randomly assigned to subsequently receive an autologous transfusion of either fresh (2-days-old) or stored (7-days-old) platelets, or saline control. Extracellular vesicles (EVs) were determined using flow cytometry, thrombin–antithrombin complex (TATc) was assessed using enzyme-linked immunosorbent assay, and hemostatic function was assessed using rotational thromboelastometry (ROTEM).
Results
LPS infusion caused a marked increase in TATc, EVs and fibrinolysis. Thromboelastometry data revealed that following infusion of LPS, subjects exhibited in general a hypocoagulable state compared with those not receiving LPS. Platelet transfusions led to a reduced clotting time and an augmentation in clot strength, indicated by maximum clot firmness, solely among subjects undergoing endotoxemia. There were no significant differences in TATc or amount of EVs release after transfusion of fresh or stored platelets.
Conclusion
A significant increase in TATc and EVs as well as a difference in hemostatic function after endotoxemia were observed. During endotoxemia, platelet transfusion resulted in enhanced coagulation and hemostatic function; however, no substantial differences were observed between transfusion of fresh or stored PCs.
{"title":"Hemostatic conditions following autologous transfusion of fresh vs stored platelets in experimental endotoxemia: an open-label randomized controlled trial with healthy volunteers","authors":"Stefan F. van Wonderen , Floor L.F. van Baarle , Anita M. Tuip-de Boer , Chantal A. Polet , Robin van Bruggen , Christie Vermeulen , Thomas R.L. Klei , Chi M. Hau , Rienk Nieuwland , Cornelis van ’t Veer , Anna L. Peters , Sanne de Bruin , Alexander P.J. Vlaar , Bart J. Biemond , Marcella C.A. Müller","doi":"10.1016/j.rpth.2024.102612","DOIUrl":"10.1016/j.rpth.2024.102612","url":null,"abstract":"<div><h3>Background</h3><div>Platelet increment is reportedly lower for maximum stored platelet concentrates (PCs) and during pyrexia, and <em>in vitro</em> function differs between fresh and stored PCs. However, little is known about the function of fresh and stored platelets during inflammation.</div></div><div><h3>Objectives</h3><div>The aim was to study differences in hemostatic function after transfusion of fresh or stored PCs in a human model of experimental endotoxemia.</div></div><div><h3>Methods</h3><div>Thirty-six healthy male subjects received either 2 ng/kg lipopolysaccharide (LPS) or a control (physiological saline 0.9%) and were randomly assigned to subsequently receive an autologous transfusion of either fresh (2-days-old) or stored (7-days-old) platelets, or saline control. Extracellular vesicles (EVs) were determined using flow cytometry, thrombin–antithrombin complex (TATc) was assessed using enzyme-linked immunosorbent assay, and hemostatic function was assessed using rotational thromboelastometry (ROTEM).</div></div><div><h3>Results</h3><div>LPS infusion caused a marked increase in TATc, EVs and fibrinolysis. Thromboelastometry data revealed that following infusion of LPS, subjects exhibited in general a hypocoagulable state compared with those not receiving LPS. Platelet transfusions led to a reduced clotting time and an augmentation in clot strength, indicated by maximum clot firmness, solely among subjects undergoing endotoxemia. There were no significant differences in TATc or amount of EVs release after transfusion of fresh or stored platelets.</div></div><div><h3>Conclusion</h3><div>A significant increase in TATc and EVs as well as a difference in hemostatic function after endotoxemia were observed. During endotoxemia, platelet transfusion resulted in enhanced coagulation and hemostatic function; however, no substantial differences were observed between transfusion of fresh or stored PCs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102612"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702349","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102602
Pascal N. Tyrrell , María Teresa Alvarez-Román , Nihal Bakeer , Brigitte Brand-Staufer , Victor Jiménez-Yuste , Susan Kras , Carlo Martinoli , Mauro Mendez , Azusa Nagao , Margareth Ozelo , Janaina B.S. Ricciardi , Marek Zak , Johannes Roth
Background
Recurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia, despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient’s assessment of musculoskeletal pain may not accurately identify a joint bleed. This difficulty is compounded as hemophilic arthropathy progresses.
Objectives
Our system aims to utilize artificial intelligence and ultrasonography (US; point-of-care and handheld) to enable providers, and ultimately patients, to detect joint bleeds at the bedside and at home. We aimed to develop and assess the reliability of artificial intelligence algorithms in detecting and segmenting synovial recess distension (SRD; an indicator of disease activity) on US images of adult and pediatric knee, elbow, and ankle joints.
Methods
A total of 12,145 joint exams, comprising 61,501 US images from 7 international healthcare centers, were collected. The dataset included healthy participants and adult and pediatric persons with hemophilia, with and without SRD. Images were manually labeled by 2 experts and used to train binary convolutional neural network classifiers and segmentation models. Metrics to evaluate performance included accuracy, sensitivity, specificity, and area under the curve.
Results
The algorithms exhibited high performance across all joints and all cohorts. Specifically, the knee model showed an accuracy of 97%, sensitivity of 96%, specificity of 97%, and an area under the curve of 0.97 in SRD. High Dice coefficients (80%-85%) were achieved in segmentation tasks across all joints.
Conclusion
This technology could assist with the early detection and management of hemarthrosis in hemophilia.
{"title":"Utilizing artificial intelligence for the detection of hemarthrosis in hemophilia using point-of-care ultrasonography","authors":"Pascal N. Tyrrell , María Teresa Alvarez-Román , Nihal Bakeer , Brigitte Brand-Staufer , Victor Jiménez-Yuste , Susan Kras , Carlo Martinoli , Mauro Mendez , Azusa Nagao , Margareth Ozelo , Janaina B.S. Ricciardi , Marek Zak , Johannes Roth","doi":"10.1016/j.rpth.2024.102602","DOIUrl":"10.1016/j.rpth.2024.102602","url":null,"abstract":"<div><h3>Background</h3><div>Recurrent hemarthrosis and resultant hemophilic arthropathy are significant causes of morbidity in persons with hemophilia, despite the marked evolution of hemophilia care. Prevention, timely diagnosis, and treatment of bleeding episodes are key. However, a physical examination or a patient’s assessment of musculoskeletal pain may not accurately identify a joint bleed. This difficulty is compounded as hemophilic arthropathy progresses.</div></div><div><h3>Objectives</h3><div>Our system aims to utilize artificial intelligence and ultrasonography (US; point-of-care and handheld) to enable providers, and ultimately patients, to detect joint bleeds at the bedside and at home. We aimed to develop and assess the reliability of artificial intelligence algorithms in detecting and segmenting synovial recess distension (SRD; an indicator of disease activity) on US images of adult and pediatric knee, elbow, and ankle joints.</div></div><div><h3>Methods</h3><div>A total of 12,145 joint exams, comprising 61,501 US images from 7 international healthcare centers, were collected. The dataset included healthy participants and adult and pediatric persons with hemophilia, with and without SRD. Images were manually labeled by 2 experts and used to train binary convolutional neural network classifiers and segmentation models. Metrics to evaluate performance included accuracy, sensitivity, specificity, and area under the curve.</div></div><div><h3>Results</h3><div>The algorithms exhibited high performance across all joints and all cohorts. Specifically, the knee model showed an accuracy of 97%, sensitivity of 96%, specificity of 97%, and an area under the curve of 0.97 in SRD. High Dice coefficients (80%-85%) were achieved in segmentation tasks across all joints.</div></div><div><h3>Conclusion</h3><div>This technology could assist with the early detection and management of hemarthrosis in hemophilia.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102602"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142723701","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102609
James Shih MD , Chu-Shu Gu PhD , Suresh Vedantham MD , John Kaufman MD , Susan R. Kahn MD
Background
The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.
Objectives
Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.
Methods
Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for mean total VS score, VS symptoms score, VS signs score, individual signs scores, and correlation coefficients between VS signs and VS symptoms scores and between VS signs and Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores (a self-reported venous disease-specific quality of life measure).
Results
Mean total VS score (4.67 vs. 4.12, P = .54),VS signs score (1.66 vs. 2.00, P = .07), and VS symptoms score (2.83 vs. 2.04, P = .10) were similar between Black and White participants. The mean score for one individual VS sign, venous ectasia, was lower in Black vs. White participants (0.24 vs. 0.63, P< .01). There was similar, modest correlation in Black and White participants between VS signs and VS symptoms scores (rblack = 0.19; rwhite = 0.23) and between VS signs and VEINES-QOL scores (rblack = −0.32; rwhite = −0.30). Results were adjusted for ATTRACT trial treatment group, age, sex, body mass index, DVT extent, hypertension, diabetes, dyslipidemia, and congestive heart failure.
Conclusion
The findings suggest that some differences in VS scores exist according to self-reported race. It is unclear whether these reflect clinicians’ underrating of some VS signs and/or differences in PTS severity. Further work is needed to understand how the VS performs across racial groups.
背景诊断血栓后综合征(PTS)的 Villalta 量表(VS)由患者报告的 5 个腿部症状和临床医生评定的 6 个腿部体征组成。方法对 ATTRACT 试验进行探索性分析,该试验是一项随机对照试验,在美国 56 个地点进行,研究了药物机械导管引导溶栓以预防近端深静脉血栓 (DVT) 后的 PTS。在随机化后 6 个月的回访中,我们比较了黑人(n = 123)和白人(n = 541)参与者自我报告的平均 VS 总分、VS 症状分、VS 体征分、单个体征分、VS 体征与 VS 症状分之间的相关系数以及 VS 体征与静脉功能不全流行病学和经济学生活质量研究 (VEINES-QOL) 分(一种自我报告的静脉疾病特异性生活质量测量指标)之间的相关系数。结果 黑人和白人参与者的平均 VS 总分(4.67 vs. 4.12,P = .54)、VS 体征得分(1.66 vs. 2.00,P = .07)和 VS 症状得分(2.83 vs. 2.04,P = .10)相似。黑人和白人参加者在静脉异位这一 VS 征兆上的平均得分较低(0.24 vs. 0.63,P< .01)。在黑人和白人参与者中,VS 征兆和 VS 症状评分之间(黑人 = 0.19;白人 = 0.23)以及 VS 征兆和 VEINES-QOL 评分之间(黑人 = -0.32;白人 = -0.30)存在类似的适度相关性。结果根据 ATTRACT 试验治疗组、年龄、性别、体重指数、深静脉血栓程度、高血压、糖尿病、血脂异常和充血性心力衰竭进行了调整。目前还不清楚这是否反映了临床医生对某些 VS 征兆的低估和/或 PTS 严重程度的差异。要了解 VS 在不同种族群体中的表现,还需要进一步的研究。
{"title":"Impact of self-reported race on Villalta Scale postthrombotic syndrome scores and correlation with venous disease-specific quality of life: an exploratory analysis of the Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis Trial","authors":"James Shih MD , Chu-Shu Gu PhD , Suresh Vedantham MD , John Kaufman MD , Susan R. Kahn MD","doi":"10.1016/j.rpth.2024.102609","DOIUrl":"10.1016/j.rpth.2024.102609","url":null,"abstract":"<div><h3>Background</h3><div>The Villalta Scale (VS) to diagnose postthrombotic syndrome (PTS) consists of 5 patient-reported leg symptoms and 6 clinician-rated leg signs. It is unknown how the scale performs across racial groups.</div></div><div><h3>Objectives</h3><div>Our study explored if there were differences in VS scores, particularly clinician-rated signs components, according to self-reported race.</div></div><div><h3>Methods</h3><div>Exploratory analysis of the ATTRACT trial, a randomized controlled trial conducted at 56 US sites that investigated pharmacomechanical catheter-directed thrombolysis to prevent PTS after proximal deep vein thrombosis (DVT). At the 6-month visit after randomization, we compared self-reported Black (n = 123) and White (n = 541) participants for mean total VS score, VS symptoms score, VS signs score, individual signs scores, and correlation coefficients between VS signs and VS symptoms scores and between VS signs and Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores (a self-reported venous disease-specific quality of life measure).</div></div><div><h3>Results</h3><div>Mean total VS score (4.67 vs. 4.12, <em>P</em> = .54),VS signs score (1.66 vs. 2.00, <em>P</em> = .07), and VS symptoms score (2.83 vs. 2.04, <em>P</em> = .10) were similar between Black and White participants. The mean score for one individual VS sign, venous ectasia, was lower in Black vs. White participants (0.24 vs. 0.63, <em>P</em>< .01). There was similar, modest correlation in Black and White participants between VS signs and VS symptoms scores (<em>r</em><sub>black</sub> = 0.19; <em>r</em><sub>white</sub> = 0.23) and between VS signs and VEINES-QOL scores (<em>r</em><sub>black</sub> = −0.32; <em>r</em><sub>white</sub> = −0.30). Results were adjusted for ATTRACT trial treatment group, age, sex, body mass index, DVT extent, hypertension, diabetes, dyslipidemia, and congestive heart failure.</div></div><div><h3>Conclusion</h3><div>The findings suggest that some differences in VS scores exist according to self-reported race. It is unclear whether these reflect clinicians’ underrating of some VS signs and/or differences in PTS severity. Further work is needed to understand how the VS performs across racial groups.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102609"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702286","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102595
Syna Miri , Frits R. Rosendaal , Kaan Kavakli , Peyman Eshghi , Soha Mohammadi Moghaddam , Sara Scardo , Behnaz Habibpanah , Mohsen Elalfy , Susan Halimeh , Gabriella Nicolò , Dilek Gökçebay , Namık Özbek , Tiraje Celkan , Ahmad Mohammadi , Mehran Karimi , Amin Shahsavani , Bariş Yılmaz , Canan Albayrak , Burcak Gunes , Zühre Kaya , Flora Peyvandi
Background
The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.
Objectives
We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears.
Methods
The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch.
Results
Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%).
Conclusion
PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.
{"title":"Inhibitor development upon switching from plasma-derived to recombinant factor VIII in previously untreated patients with severe hemophilia A: the PUP-SWITCH study","authors":"Syna Miri , Frits R. Rosendaal , Kaan Kavakli , Peyman Eshghi , Soha Mohammadi Moghaddam , Sara Scardo , Behnaz Habibpanah , Mohsen Elalfy , Susan Halimeh , Gabriella Nicolò , Dilek Gökçebay , Namık Özbek , Tiraje Celkan , Ahmad Mohammadi , Mehran Karimi , Amin Shahsavani , Bariş Yılmaz , Canan Albayrak , Burcak Gunes , Zühre Kaya , Flora Peyvandi","doi":"10.1016/j.rpth.2024.102595","DOIUrl":"10.1016/j.rpth.2024.102595","url":null,"abstract":"<div><h3>Background</h3><div>The SIPPET randomized clinical trial showed that in previously untreated patients (PUPs) with severe hemophilia A, treatment with plasma-derived factor (F)VIII (pdFVIII) within the first 50 exposure days (EDs) was associated with a lower cumulative incidence of inhibitors than with recombinant FVIII (rFVIII). Switching to rFVIII beyond 50 EDs with pdFVIII is a treatment often implemented by many centers. The question is whether or not this switch may induce a risk of inhibitor development.</div></div><div><h3>Objectives</h3><div>We investigated if in PUPs with severe hemophilia A switched after 50 EDs from pdFVIII to rFVIII, a novel inhibitor peak appears.</div></div><div><h3>Methods</h3><div>The PUP-SWITCH observational retrospective study was designed to investigate the cumulative incidence of novel inhibitors after switching PUPs to rFVIII after 50 and before 150 EDs. Hemophilia centers that routinely switched PUPs from pdFVIII to rFVIII within this exposure time frame were invited to participate. Patients were followed up for at least 50 EDs after the switch.</div></div><div><h3>Results</h3><div>Ninety-seven patients were evaluated, and 87 were included according to eligibility criteria between 2020 and 2022. Only one of them developed an inhibitor 20 EDs after switching, so the cumulative incidence was 1.15% (95% CI, 0.03%-6.24%).</div></div><div><h3>Conclusion</h3><div>PUP-SWITCH, a study focusing on PUPs undergoing a product class switch from pdFVIII to rFVIII after 50 EDs, showed that switching appears to be safe pertaining to the risk of development of new inhibitors.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102595"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702288","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}
Serum thromboxane B2 (sTXB2) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 °C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB2 measurements. The storage duration of frozen serum can also affect sTXB2 stability.
Objectives
We assessed the stability of sTXB2 in clotted blood samples stored at 4 °C before further processing and in sera stored at −40 °C for over a decade.
Methods
Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 °C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 °C for 12 to 72 hours before further processing. Sera stored at a controlled −40 °C temperature for <1 to 15 years were reassayed. Values within the interassay variation limits (±9%) vs baseline were considered acceptable.
Results
Baseline sTXB2 values (median, 5.4 ng/mL; IQR, 2.4-13.4 ng/mL; n = 40) were comparable with those in samples at 4 °C up to 48 hours (median, 97% [IQR, 86%-104%] of the reference; n = 26), but at 72 hours, the variability exceeded the interassay variation. Thromboxane B2 levels were stable in frozen sera for up to 10 years (median, 101% [IQR, 87%-108%] of the reference; n = 32) but decreased significantly afterward (median, 87% [IQR, 74%-109%] at 15 years; P = .005; n = 32).
Conclusion
Thromboxane B2 is stable in clotted blood samples stored at 4 °C for up to 48 hours before further processing and in serum samples stored at −40 °C over 10 years.
{"title":"Stability of the thromboxane B2 biomarker of low-dose aspirin pharmacodynamics in human whole blood and in long-term stored serum samples","authors":"Giovanna Petrucci , Alessandro Rizzi , Simone Bellavia , Francesco Dentali , Giovanni Frisullo , Dario Pitocco , Paola Ranalli , Pier Andrea Rizzo , Irene Scala , Mauro Silingardi , Elisa Zagarrì , Gualberto Gussoni , Bianca Rocca","doi":"10.1016/j.rpth.2024.102623","DOIUrl":"10.1016/j.rpth.2024.102623","url":null,"abstract":"<div><h3>Background</h3><div>Serum thromboxane B<sub>2</sub> (sTXB<sub>2</sub>) is a validated biomarker of low-dose aspirin pharmacodynamics. In the original method, nonanticoagulated blood samples must be incubated at 37 °C immediately after withdrawal, centrifuged and serum supernatant should be frozen until assayed. Timely completion of all preanalytical steps may affect the feasibility and quality of sTXB<sub>2</sub> measurements. The storage duration of frozen serum can also affect sTXB<sub>2</sub> stability.</div></div><div><h3>Objectives</h3><div>We assessed the stability of sTXB<sub>2</sub> in clotted blood samples stored at 4 °C before further processing and in sera stored at −40 °C for over a decade.</div></div><div><h3>Methods</h3><div>Venous whole blood withdrawn from individuals on chronic low-dose aspirin was dispensed in different tubes and immediately incubated at 37 °C for 1 hour. The reference tube was promptly processed following the original protocol; the remaining tubes were stored at 4 °C for 12 to 72 hours before further processing. Sera stored at a controlled −40 °C temperature for <1 to 15 years were reassayed. Values within the interassay variation limits (±9%) vs baseline were considered acceptable.</div></div><div><h3>Results</h3><div>Baseline sTXB<sub>2</sub> values (median, 5.4 ng/mL; IQR, 2.4-13.4 ng/mL; <em>n</em> = 40) were comparable with those in samples at 4 °C up to 48 hours (median, 97% [IQR, 86%-104%] of the reference; <em>n</em> = 26), but at 72 hours, the variability exceeded the interassay variation. Thromboxane B<sub>2</sub> levels were stable in frozen sera for up to 10 years (median, 101% [IQR, 87%-108%] of the reference; <em>n</em> = 32) but decreased significantly afterward (median, 87% [IQR, 74%-109%] at 15 years; <em>P</em> = .005; <em>n</em> = 32).</div></div><div><h3>Conclusion</h3><div>Thromboxane B<sub>2</sub> is stable in clotted blood samples stored at 4 °C for up to 48 hours before further processing and in serum samples stored at −40 °C over 10 years.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102623"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759317","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102613
Davide Di Vece , Marco Valgimigli , Elliot Barnathan , Jean M. Connors , Frank Cools , Ulrike Held , Ajay K. Kakkar , Gregory Piazza , David Spirk , Saverio Virdone , Nils Kucher , Stefano Barco
Background
The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication.
Objectives
The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19. The study protocol was registered in PROSPERO (CRD42022362776).
Methods
The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducted a comprehensive search of PubMed/MEDLINE, ClinicalTrials.gov, and OVID/Embase and CENTRAL from Cochrane for studies up to December 11, 2023, without language restrictions. Randomized controlled trials comparing prophylactic-dose anticoagulation with placebo or standard of care in symptomatic outpatients with COVID-19 were included in this analysis. The primary outcome was the composite of all-cause hospitalization and death within 30 days. Secondary outcomes included venous thromboembolism, the composite of venous thromboembolism and major arterial cardiovascular events, and the individual components of the primary outcome.
Results
Seven randomized controlled trials and 3758 COVID-19 outpatients were included. When compared with placebo or standard of care, thromboprophylaxis was associated with similar rates of all-cause hospitalization or mortality (relative risk, 1.00; 95% CI, 0.77-1.31) and lower rates of venous thromboembolism (relative risk, 0.28; 95% CI, 0.08-0.94), corresponding to a 0.6% absolute risk reduction and number needed to treat of 174.
Conclusion
Thromboprophylaxis in symptomatic COVID-19 outpatients led to reduction in venous thromboembolism risk, with no impact on hospitalization or death. However, the overall low absolute risk reduction may not support its routine use.
{"title":"Primary thromboprophylaxis in ambulatory symptomatic patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials","authors":"Davide Di Vece , Marco Valgimigli , Elliot Barnathan , Jean M. Connors , Frank Cools , Ulrike Held , Ajay K. Kakkar , Gregory Piazza , David Spirk , Saverio Virdone , Nils Kucher , Stefano Barco","doi":"10.1016/j.rpth.2024.102613","DOIUrl":"10.1016/j.rpth.2024.102613","url":null,"abstract":"<div><h3>Background</h3><div>The global impact of the COVID-19 pandemic has prompted the search for strategies to improve outcomes in affected individuals, including those initially managed in outpatient settings. Thromboembolic events have been reported as a concerning complication.</div></div><div><h3>Objectives</h3><div>The aim of this study was to evaluate efficacy and safety of primary thromboprophylaxis in outpatients with COVID-19. The study protocol was registered in PROSPERO (CRD42022362776).</div></div><div><h3>Methods</h3><div>The study adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and conducted a comprehensive search of PubMed/MEDLINE, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and OVID/Embase and CENTRAL from Cochrane for studies up to December 11, 2023, without language restrictions. Randomized controlled trials comparing prophylactic-dose anticoagulation with placebo or standard of care in symptomatic outpatients with COVID-19 were included in this analysis. The primary outcome was the composite of all-cause hospitalization and death within 30 days. Secondary outcomes included venous thromboembolism, the composite of venous thromboembolism and major arterial cardiovascular events, and the individual components of the primary outcome.</div></div><div><h3>Results</h3><div>Seven randomized controlled trials and 3758 COVID-19 outpatients were included. When compared with placebo or standard of care, thromboprophylaxis was associated with similar rates of all-cause hospitalization or mortality (relative risk, 1.00; 95% CI, 0.77-1.31) and lower rates of venous thromboembolism (relative risk, 0.28; 95% CI, 0.08-0.94), corresponding to a 0.6% absolute risk reduction and number needed to treat of 174.</div></div><div><h3>Conclusion</h3><div>Thromboprophylaxis in symptomatic COVID-19 outpatients led to reduction in venous thromboembolism risk, with no impact on hospitalization or death. However, the overall low absolute risk reduction may not support its routine use.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102613"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759318","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102606
Priyanka Sridhar , Hong Yu Wang , Agostina Velo , Destiny Nguyen , Avinash Singh , Abdul Rehman , Jason Filopei , Madeline Ehrlich , Robert Lookstein , David J. Steiger
Background
Interhospital transfer (IHT) for acute pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies. It is unclear if outcomes of patients undergoing IHT are comparable with those of patients presenting in-house to hospitals with PE Response Team (PERT) capabilities.
Objectives
To determine whether outcomes of patients with acute PE undergoing IHT differ from those of patients presenting in-house.
Methods
We retrospectively reviewed 386 patients with acute PE who were treated by PERT at 1 of 3 urban teaching hospitals in the Mount Sinai Health System in New York City from January 2021 to October 2023. Propensity score–weighted analysis was performed to compare the outcomes of patients managed in-house with those of patients undergoing IHT.
Results
Two hundred eighty-four patients presented in-house, while 102 were transferred from other hospitals. Median PE Severity Index score was 84, and 3 (0.8%), 80 (20.7%), 237 (61.4%), and 66 (17.1%) had low-risk, intermediate low–risk, intermediate high–risk, and high-risk PE. Odds of receiving systemic thrombolysis (odds ratio [OR], 1.06; P = .06) or advanced therapies (OR, 0.95; P = .003) were not significantly different between the 2 groups. Rates of 30-day mortality, major bleeding, and readmission were 6.9%, 2.9%, and 9.8% for the IHT group and 10.6%, 2.1%, and 13% for the in-house group, respectively. IHT patients had lower odds of 30-day mortality (OR, 0.88; P = .003) and higher odds of major bleeding (OR, 1.03; P = .04).
Conclusion
PERT-guided IHT for patients with acute PE was associated with reduced mortality but increased risk of bleeding compared with patients managed in-house at hospitals with PERT capabilities.
{"title":"Outcomes of patients with acute pulmonary embolism managed in-house vs those transferred between hospitals: a retrospective observational study","authors":"Priyanka Sridhar , Hong Yu Wang , Agostina Velo , Destiny Nguyen , Avinash Singh , Abdul Rehman , Jason Filopei , Madeline Ehrlich , Robert Lookstein , David J. Steiger","doi":"10.1016/j.rpth.2024.102606","DOIUrl":"10.1016/j.rpth.2024.102606","url":null,"abstract":"<div><h3>Background</h3><div>Interhospital transfer (IHT) for acute pulmonary embolism (PE) is increasingly performed to improve access to advanced reperfusion therapies. It is unclear if outcomes of patients undergoing IHT are comparable with those of patients presenting in-house to hospitals with PE Response Team (PERT) capabilities.</div></div><div><h3>Objectives</h3><div>To determine whether outcomes of patients with acute PE undergoing IHT differ from those of patients presenting in-house.</div></div><div><h3>Methods</h3><div>We retrospectively reviewed 386 patients with acute PE who were treated by PERT at 1 of 3 urban teaching hospitals in the Mount Sinai Health System in New York City from January 2021 to October 2023. Propensity score–weighted analysis was performed to compare the outcomes of patients managed in-house with those of patients undergoing IHT.</div></div><div><h3>Results</h3><div>Two hundred eighty-four patients presented in-house, while 102 were transferred from other hospitals. Median PE Severity Index score was 84, and 3 (0.8%), 80 (20.7%), 237 (61.4%), and 66 (17.1%) had low-risk, intermediate low–risk, intermediate high–risk, and high-risk PE. Odds of receiving systemic thrombolysis (odds ratio [OR], 1.06; <em>P</em> = .06) or advanced therapies (OR, 0.95; <em>P</em> = .003) were not significantly different between the 2 groups. Rates of 30-day mortality, major bleeding, and readmission were 6.9%, 2.9%, and 9.8% for the IHT group and 10.6%, 2.1%, and 13% for the in-house group, respectively. IHT patients had lower odds of 30-day mortality (OR, 0.88; <em>P</em> = .003) and higher odds of major bleeding (OR, 1.03; <em>P</em> = .04).</div></div><div><h3>Conclusion</h3><div>PERT-guided IHT for patients with acute PE was associated with reduced mortality but increased risk of bleeding compared with patients managed in-house at hospitals with PERT capabilities.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102606"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748723","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 : 2024-11-01DOI: 10.1016/j.rpth.2024.102611
Ragnhild J. Måseide MD, PhD , Erik Berntorp MD, PhD , Jan Astermark MD, PhD , Anna Olsson MD, PhD , Maria Bruzelius MD, PhD , Tony Frisk MD, PhD , Vuokko Nummi MD, PhD , Riitta Lassila MD, PhD , Karin Strandberg MD, PhD , Geir E. Tjønnfjord MD, PhD , Pål A. Holme MD, PhD
Background
The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.
Objectives
To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.
Methods
A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway. Inhibitors were analyzed with the Bethesda assay, and NNAs were detected by enzyme-linked immunosorbent assay.
Results
Plasma samples from 137 MoHem study participants (median age 29 years; Q1-Q3, 15-54) were analyzed. NNAs were present in 11 of 82 (13%) of people with MHA and 7 of 55 (13%) of those with MHB irrespective of prophylactic or on-demand treatment, most frequently after 150 exposure days (EDs). Three NNA positive patients had a history of high-titer inhibitor, but current analyses were negative (<0.6 BU/mL). Baseline FVIII/FIX activity was similar among NNA positive and negative patients. Current bleeding rates were low, but patients with NNAs captured a higher Hemophilia Joint Health Score (7 [median]; Q1-Q3, 3-20 vs. 4; 1-9) (P = .02) and had more frequently undergone arthroplasty or arthrodesis (5 [33%] vs. 15 [13%]) (P = .03).
Conclusion
NNAs were detected in 13% of Nordic persons with MHA and MHB, most frequently after 150 EDs. Patients with NNAs had more severe hemophilic arthropathy than patients without NNAs. The relationship between NNAs and clinical outcome in hemophilia should be further explored in a large cohort including pharmacokinetics and longitudinal observations with repeated blood sampling.
背景非中性抗体(NNAs)对中度血友病的影响尚不明确。目的探讨北欧中度血友病 A(MHA)和 B(MHB)患者体内 NNAs 的存在与治疗方式、临床结果、抑制剂史以及相应的因子 VIII (FVIII)/ 因子 IX (FIX) 基因突变的关系。结果分析了 137 名 MoHem 研究参与者(中位年龄 29 岁;Q1-Q3,15-54 岁)的血浆样本。无论是否进行预防性治疗或按需治疗,82 名 MHA 患者中有 11 人(13%)和 55 名 MHB 患者中有 7 人(13%)存在 NNA,最常出现在暴露 150 天 (ED) 之后。三名 NNA 阳性患者曾出现高滴度抑制剂,但目前的分析结果为阴性(0.6 BU/mL)。NNA 阳性和阴性患者的基线 FVIII/FIX 活性相似。目前的出血率较低,但 NNA 患者的血友病关节健康评分较高(7 [中位数];Q1-Q3,3-20 vs. 4;1-9)(P = .02),且更常接受关节成形术或关节固定术(5 [33%] vs. 15 [13%])(P = .03)。与无 NNA 的患者相比,有 NNA 的患者血友病关节病更为严重。NNAs与血友病临床结果之间的关系应在大型队列中进一步探讨,包括药代动力学和重复采血的纵向观察。
{"title":"Nonneutralizing antibodies in Nordic persons with moderate hemophilia A and B (the MoHem study)","authors":"Ragnhild J. Måseide MD, PhD , Erik Berntorp MD, PhD , Jan Astermark MD, PhD , Anna Olsson MD, PhD , Maria Bruzelius MD, PhD , Tony Frisk MD, PhD , Vuokko Nummi MD, PhD , Riitta Lassila MD, PhD , Karin Strandberg MD, PhD , Geir E. Tjønnfjord MD, PhD , Pål A. Holme MD, PhD","doi":"10.1016/j.rpth.2024.102611","DOIUrl":"10.1016/j.rpth.2024.102611","url":null,"abstract":"<div><h3>Background</h3><div>The impact of nonneutralizing antibodies (NNAs) in moderate hemophilia is elusive.</div></div><div><h3>Objectives</h3><div>To explore the presence of NNAs in Nordic persons with moderate hemophilia A (MHA) and B (MHB) in relation to treatment modality, clinical outcome, history of inhibitor, and the corresponding factor VIII (FVIII)/factor IX (FIX) gene mutation.</div></div><div><h3>Methods</h3><div>A cross-sectional multicenter study covering persons with MHA and MHB in Sweden, Finland, and Norway. Inhibitors were analyzed with the Bethesda assay, and NNAs were detected by enzyme-linked immunosorbent assay.</div></div><div><h3>Results</h3><div>Plasma samples from 137 MoHem study participants (median age 29 years; Q1-Q3, 15-54) were analyzed. NNAs were present in 11 of 82 (13%) of people with MHA and 7 of 55 (13%) of those with MHB irrespective of prophylactic or on-demand treatment, most frequently after 150 exposure days (EDs). Three NNA positive patients had a history of high-titer inhibitor, but current analyses were negative (<0.6 BU/mL). Baseline FVIII/FIX activity was similar among NNA positive and negative patients. Current bleeding rates were low, but patients with NNAs captured a higher Hemophilia Joint Health Score (7 [median]; Q1-Q3, 3-20 vs. 4; 1-9) (<em>P</em> = .02) and had more frequently undergone arthroplasty or arthrodesis (5 [33%] vs. 15 [13%]) (<em>P</em> = .03).</div></div><div><h3>Conclusion</h3><div>NNAs were detected in 13% of Nordic persons with MHA and MHB, most frequently after 150 EDs. Patients with NNAs had more severe hemophilic arthropathy than patients without NNAs. The relationship between NNAs and clinical outcome in hemophilia should be further explored in a large cohort including pharmacokinetics and longitudinal observations with repeated blood sampling.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102611"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142702285","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}