Pub Date : 2024-07-01DOI: 10.1016/j.rpth.2024.102537
Background
Heparin-induced thrombocytopenia (HIT) is a complication of heparin exposure associated with high risk for morbidity and mortality. Diagnosis and management are complex due to limitations of laboratory testing and the need for nonheparin anticoagulation.
Objectives
To increase the delivery of evidence-based care of patients with suspected and confirmed HIT via electronic consultation (e-consult).
Methods
We describe the creation and implementation of an e-consult service for patients with concern for HIT at a large academic medical center. Hematology physicians with HIT expertise performed real-time chart review of all patients with a positive screening immunoassay result and provided written recommendations in their electronic health record.
Results
Comparison of outcomes for 1 year before and the year after the e-consult service implementation identified improvements in direct thrombin inhibitor stewardship, increased diagnostic accuracy, and decreased length of stay of patients with confirmed HIT.
Conclusion
The e-consult platform is a novel method for rapid, targeted consultative guidance, and this single-institution pilot demonstrates its feasibility and effectiveness to improve the care of patients with suspected and confirmed HIT.
背景肝素诱导的血小板减少症(HIT)是肝素暴露的一种并发症,具有很高的发病率和死亡率风险。由于实验室检测的局限性和非肝素抗凝的需要,诊断和管理都很复杂。目标通过电子会诊(e-consult)为疑似和确诊 HIT 患者提供更多循证护理。方法我们介绍了一家大型学术医疗中心为疑似 HIT 患者创建和实施电子会诊服务的情况。具有 HIT 专业知识的血液科医生对所有筛查免疫测定结果呈阳性的患者进行实时病历审查,并在其电子健康记录中提供书面建议。结果对电子会诊服务实施前一年和实施后一年的结果进行比较,发现直接凝血酶抑制剂管理得到改善,诊断准确性提高,确诊 HIT 患者的住院时间缩短。结论电子会诊平台是一种快速、有针对性的会诊指导新方法,这一单一机构试点证明了它在改善疑似和确诊 HIT 患者护理方面的可行性和有效性。
{"title":"Electronic consultation to improve care outcomes in patients with suspected and confirmed heparin-induced thrombocytopenia","authors":"","doi":"10.1016/j.rpth.2024.102537","DOIUrl":"10.1016/j.rpth.2024.102537","url":null,"abstract":"<div><h3>Background</h3><p>Heparin-induced thrombocytopenia (HIT) is a complication of heparin exposure associated with high risk for morbidity and mortality. Diagnosis and management are complex due to limitations of laboratory testing and the need for nonheparin anticoagulation.</p></div><div><h3>Objectives</h3><p>To increase the delivery of evidence-based care of patients with suspected and confirmed HIT via electronic consultation (e-consult).</p></div><div><h3>Methods</h3><p>We describe the creation and implementation of an e-consult service for patients with concern for HIT at a large academic medical center. Hematology physicians with HIT expertise performed real-time chart review of all patients with a positive screening immunoassay result and provided written recommendations in their electronic health record.</p></div><div><h3>Results</h3><p>Comparison of outcomes for 1 year before and the year after the e-consult service implementation identified improvements in direct thrombin inhibitor stewardship, increased diagnostic accuracy, and decreased length of stay of patients with confirmed HIT.</p></div><div><h3>Conclusion</h3><p>The e-consult platform is a novel method for rapid, targeted consultative guidance, and this single-institution pilot demonstrates its feasibility and effectiveness to improve the care of patients with suspected and confirmed HIT.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002322/pdfft?md5=7067530a512971801c429b8c77ca58be&pid=1-s2.0-S2475037924002322-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021478","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102525
Background
Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management.
Objectives
To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti–ADAMTS-13 autoantibodies (AAbs) in patients with iTTP.
Methods
This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL).
Results
For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [−0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (P < .001, Cohen’s g = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations.
Conclusion
While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.
{"title":"A comparative study of anti–ADAMTS-13 antibody dynamics in immune-mediated thrombotic thrombocytopenic purpura","authors":"","doi":"10.1016/j.rpth.2024.102525","DOIUrl":"10.1016/j.rpth.2024.102525","url":null,"abstract":"<div><h3>Background</h3><p>Thrombotic thrombocytopenic purpura, particularly its immune-mediated variant (iTTP), necessitates accurate diagnostic approaches for effective management.</p></div><div><h3>Objectives</h3><p>To compare a chemiluminescence immunoassay (CLIA) and an enzyme-linked immunosorbent assay (ELISA) for testing ADAMTS-13 activity and detecting anti–ADAMTS-13 autoantibodies (AAbs) in patients with iTTP.</p></div><div><h3>Methods</h3><p>This study involved 31 paired samples from 12 iTTP patients. ADAMTS-13 activity was measured using the HemosIL AcuStar (Instrumentation Laboratory, CLIA) and Technozym (Technoclone) activity assay (ELISA). The presence of AAbs was assessed using Technozym ADAMTS-13-INH assay (ELISA) and HemosIL AcuStar activity (CLIA) within a Bethesda assay following mixing with normal pool plasma. von Willebrand factor (VWF) multimers were analyzed using the HYDRASYS-2 SCAN system and the HYDRAGEL 5- or 11-VW Multimer kits (Sebia). VWF activity levels were measured with the HemosIL AcuStar VWF:GPIbR on the ACL AcuStar Analyzer (IL).</p></div><div><h3>Results</h3><p>For ADAMTS-13 activity, a strong linear relationship and no bias between CLIA and ELISA were confirmed (slope = 1.01 [0.91, 1.11], intercept = 0.00 [−0.47, 0]). However, significant discrepancies were found in AAb detection during remission phases with ADAMTS-13 activity between 10% and 50%, with CLIA and ELISA showing significant divergence (<em>P</em> < .001, Cohen’s <em>g</em> = 0.34). Consistently, VWF multimers and activity levels exhibited significantly different values between remission samples with ADAMTS-13 activity below 50% and above 50%. In longitudinal analysis of patients with multiple iTTP relapses, positivity to CLIA appears to precede ELISA in predicting exacerbations.</p></div><div><h3>Conclusion</h3><p>While CLIA and ELISA might be interchangeable for assessing ADAMTS-13 activity, they are not equivalent for detecting AAbs, particularly in patients in clinical remission with ADAMTS-13 activity between 10% and 50%.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002206/pdfft?md5=7143bb4fa2511d15665bb37915bb94de&pid=1-s2.0-S2475037924002206-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141852314","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102508
Background
Between 2002 and 2011, the incidence of severe primary postpartum hemorrhage (PPH) in Dutch women with von Willebrand disease (VWD) and hemophilia carriers (HCs) was 8% vs 4.5% in the general population.
Objectives
To determine the contemporary incidence of severe primary PPH in women with VWD and HCs.
Methods
All women with VWD or HCs who delivered between 2012 and 2017 were selected from all 6 Dutch hemophilia treatment centers. Data on patient and disease characteristics, peripartum hematologic and obstetric management, and outcomes were retrospectively collected. Incidence of severe primary (≥1000 mL of blood loss ≤24 hours after childbirth) and primary (≥500 mL within ≤24 hours after childbirth) PPH was compared with the (1) previous cohort and (2) general Dutch population and between (3) women with VWD and HCs with third-trimester coagulation activity levels <50 international units (IU)/dL vs ≥50 IU/dL and (4) women treated with vs without peripartum hemostatic prophylaxis.
Results
Three-hundred forty-eight deliveries (151 VWD, 167 hemophilia A, and 30 hemophilia B carriers) were included. The severe primary PPH incidence was 10% (36/348) and remained stable over time, whereas this incidence has increased in the general population (to 8%), leading to a similar risk (P = .17). Severe primary PPH risk was comparable between women with coagulation activity levels <50 and ≥50 IU/dL (11% [7/66] vs 10% [29/279]; odds ratio, 1.02; 95% CI, 0.43-2.44) and comparable between those with and those without prophylaxis (12% [11/91] vs 10% [25/254]; odds ratio, 1.26; 95% CI, 0.59-2.68).
Conclusion
Severe primary PPH in women with VWD and HCs remained stable and is comparable with the increasing prevalence in the general population. More research is needed to find the optimal pregnancy management strategy for safe delivery in VWD and HC.
背景2002年至2011年间,荷兰冯-威廉氏病(VWD)和血友病携带者(HCs)妇女严重原发性产后出血(PPH)的发病率为8%,而普通人群的发病率为4.5%.Objectives To determine the contemporary incidence of severe primary PPH in women with VWD and HCs.Methods从所有6个荷兰血友病治疗中心选取了2012年至2017年间分娩的所有冯-威廉氏病或血友病妇女。回顾性收集有关患者和疾病特征、围产期血液学和产科管理以及结果的数据。将严重原发性(分娩后≤24小时内失血量≥1000毫升)和原发性(分娩后≤24小时内失血量≥500毫升)PPH的发生率与(1)之前的队列和(2)荷兰总人口进行了比较,并比较了(3)第三孕期凝血活性水平为<50国际单位(IU)/dL vs ≥50 IU/dL的VWD和HC妇女和(4)接受了围产期止血预防治疗 vs 未接受围产期止血预防治疗的妇女。结果共纳入 348 例分娩(151 例 VWD、167 例 A 型血友病和 30 例 B 型血友病携带者)。严重原发性 PPH 的发生率为 10%(36/348),并且随着时间的推移保持稳定,而在普通人群中这一发生率有所上升(达到 8%),导致了相似的风险(P = .17)。凝血活酶水平为 50 和≥50 IU/dL 的妇女发生严重原发性 PPH 的风险相当(11% [7/66] vs 10% [29/279];几率比,1.02;95% CI,0.43-2.44),凝血活酶水平为 50 和≥50 IU/dL 的妇女发生严重原发性 PPH 的风险相当(11% [7/66] vs 10% [29/279];几率比,1.02;95% CI,0.43-2.44)。结论VWD和HCs妇女中的严重原发性PPH保持稳定,与普通人群中不断增加的发病率相当。需要进行更多的研究,以找到对 VWD 和 HC 安全分娩的最佳妊娠管理策略。
{"title":"Primary postpartum hemorrhage in women with von Willebrand disease and carriers of hemophilia: a retrospective analysis","authors":"","doi":"10.1016/j.rpth.2024.102508","DOIUrl":"10.1016/j.rpth.2024.102508","url":null,"abstract":"<div><h3>Background</h3><p>Between 2002 and 2011, the incidence of severe primary postpartum hemorrhage (PPH) in Dutch women with von Willebrand disease (VWD) and hemophilia carriers (HCs) was 8% vs 4.5% in the general population.</p></div><div><h3>Objectives</h3><p>To determine the contemporary incidence of severe primary PPH in women with VWD and HCs.</p></div><div><h3>Methods</h3><p>All women with VWD or HCs who delivered between 2012 and 2017 were selected from all 6 Dutch hemophilia treatment centers. Data on patient and disease characteristics, peripartum hematologic and obstetric management, and outcomes were retrospectively collected. Incidence of severe primary (≥1000 mL of blood loss ≤24 hours after childbirth) and primary (≥500 mL within ≤24 hours after childbirth) PPH was compared with the (1) previous cohort and (2) general Dutch population and between (3) women with VWD and HCs with third-trimester coagulation activity levels <50 international units (IU)/dL vs ≥50 IU/dL and (4) women treated with vs without peripartum hemostatic prophylaxis.</p></div><div><h3>Results</h3><p>Three-hundred forty-eight deliveries (151 VWD, 167 hemophilia A, and 30 hemophilia B carriers) were included. The severe primary PPH incidence was 10% (36/348) and remained stable over time, whereas this incidence has increased in the general population (to 8%), leading to a similar risk (<em>P</em> = .17). Severe primary PPH risk was comparable between women with coagulation activity levels <50 and ≥50 IU/dL (11% [7/66] vs 10% [29/279]; odds ratio, 1.02; 95% CI, 0.43-2.44) and comparable between those with and those without prophylaxis (12% [11/91] vs 10% [25/254]; odds ratio, 1.26; 95% CI, 0.59-2.68).</p></div><div><h3>Conclusion</h3><p>Severe primary PPH in women with VWD and HCs remained stable and is comparable with the increasing prevalence in the general population. More research is needed to find the optimal pregnancy management strategy for safe delivery in VWD and HC.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002036/pdfft?md5=82235e7f3354e9926883bc3fd094fb07&pid=1-s2.0-S2475037924002036-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141709996","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102468
Background
Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation.
Objectives
The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations.
Methods
This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling.
Conclusion
Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials.
{"title":"Rivaroxaban for stroke patients with antiphospholipid syndrome (RISAPS): protocol for a randomized controlled, phase IIb proof-of-principle trial","authors":"","doi":"10.1016/j.rpth.2024.102468","DOIUrl":"10.1016/j.rpth.2024.102468","url":null,"abstract":"<div><h3>Background</h3><p>Optimal secondary prevention antithrombotic therapy for patients with antiphospholipid syndrome (APS)-associated ischemic stroke, transient ischemic attack, or other ischemic brain injury is undefined. The standard of care, warfarin or other vitamin K antagonists at standard or high intensity (international normalized ratio (INR) target range 2.0-3.0/3.0-4.0, respectively), has well-recognized limitations. Direct oral anticoagulants have several advantages over warfarin, and the potential role of high-dose direct oral anticoagulants vs high-intensity warfarin in this setting merits investigation.</p></div><div><h3>Objectives</h3><p>The Rivaroxaban for Stroke patients with APS trial (RISAPS) seeks to determine whether high-dose rivaroxaban could represent a safe and effective alternative to high-intensity warfarin in adult patients with APS and previous ischemic stroke, transient ischemic attack, or other ischemic brain manifestations.</p></div><div><h3>Methods</h3><p>This phase IIb prospective, randomized, controlled, noninferiority, open-label, proof-of-principle trial compares rivaroxaban 15 mg twice daily vs warfarin, target INR range 3.0-4.0. The sample size target is 40 participants. Triple antiphospholipid antibody-positive patients are excluded. The primary efficacy outcome is the rate of change in brain white matter hyperintensity volume on magnetic resonance imaging, a surrogate marker of presumed ischemic damage, between baseline and 24 months follow-up. Secondary outcomes include additional neuroradiological and clinical measures of efficacy and safety. Exploratory outcomes include high-dose rivaroxaban pharmacokinetic modeling.</p></div><div><h3>Conclusion</h3><p>Should RISAPS demonstrate noninferior efficacy and safety of high-dose rivaroxaban in this APS subgroup, it could justify larger prospective randomized controlled trials.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924001572/pdfft?md5=b958b05928a7c6926a1754dead934faf&pid=1-s2.0-S2475037924001572-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141394118","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102516
Background
Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that usually mimics type 1 or 2A von Willebrand disease (VWD).
Key Clinical Question
Can AVWS mimic the phenotype of type 2B VWD?
Clinical Approach
A 64-year-old male patient presented with thrombocytopenia, normal routine hemostasis results, and normal VWF antigen and factor VIII levels but reduced von Willebrand factor (VWF) activity (31 IU/dL). The ristocetin-induced platelet aggregation test showed paradoxical aggregation at low doses of ristocetin, suggesting type 2B VWD, but no deleterious sequence variation was found in either the VWF or GP1BA genes, compatible with AVWS. Serum protein electrophoresis revealed a monoclonal immunoglobulin G antibody.
Conclusion
This AVWS with a 2B phenotype VWD was probably related to a monoclonal immunoglobulin G antibody causing a VWF conformational change, resulting in increased affinity to platelet glycoprotein-Ib. In the event of surgery or bleeding, treatment with vonicog alfa seems to be the best option for this patient.
{"title":"A rare case of acquired von Willebrand syndrome type 2B: diagnosis, treatment, and underlying pathophysiology","authors":"","doi":"10.1016/j.rpth.2024.102516","DOIUrl":"10.1016/j.rpth.2024.102516","url":null,"abstract":"<div><h3>Background</h3><p>Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that usually mimics type 1 or 2A von Willebrand disease (VWD).</p></div><div><h3>Key Clinical Question</h3><p>Can AVWS mimic the phenotype of type 2B VWD?</p></div><div><h3>Clinical Approach</h3><p>A 64-year-old male patient presented with thrombocytopenia, normal routine hemostasis results, and normal VWF antigen and factor VIII levels but reduced von Willebrand factor (VWF) activity (31 IU/dL). The ristocetin-induced platelet aggregation test showed paradoxical aggregation at low doses of ristocetin, suggesting type 2B VWD, but no deleterious sequence variation was found in either the <em>VWF</em> or <em>GP1BA</em> genes, compatible with AVWS. Serum protein electrophoresis revealed a monoclonal immunoglobulin G antibody.</p></div><div><h3>Conclusion</h3><p>This AVWS with a 2B phenotype VWD was probably related to a monoclonal immunoglobulin G antibody causing a VWF conformational change, resulting in increased affinity to platelet glycoprotein-Ib. In the event of surgery or bleeding, treatment with vonicog alfa seems to be the best option for this patient.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002115/pdfft?md5=f8316a779e1ace9df37c4a6b5124d1e2&pid=1-s2.0-S2475037924002115-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141846240","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102519
Background
Recent studies suggested an expected survival benefit associated with anticoagulant therapies for sepsis in patients with disseminated intravascular coagulation (DIC). However, anticoagulant therapies for overt DIC are no longer assumed to regulate pathologic progression as overt DIC is a late-phase coagulation disorder. Therefore, methods for early prediction of sepsis-induced DIC before its progression to an overt stage are strongly required.
Objectives
We aimed to develop a prediction model for overt DIC using machine learning.
Methods
This retrospective, observational study included adult septic patients without overt DIC. The objective variable was binary classification of whether patients developed overt DIC based on International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. Explanatory variables were the baseline and time series data within 7 days from sepsis diagnosis. Light Gradient Boosted Machine method was used to construct the prediction model. For controls, we assessed sensitivity and specificity of Japanese Association for Acute Medicine DIC criteria and ISTH sepsis-induced coagulopathy criteria for subsequent onset of overt DIC.
Results
Among 912 patients with sepsis, 139 patients developed overt DIC within 7 days from diagnosis of sepsis. Sensitivity, specificity, and area under the receiver operating characteristic curve for predicting onset of overt DIC within 7 days were 84.4%, 87.5%, and 0.867 in the test cohort and 95.0%, 75.9%, and 0.851 in the validation cohort, respectively. Sensitivity and specificity by the diagnostic thresholds were 54.7% and 74.9% for Japanese Association for Acute Medicine DIC criteria and 63.3% and 71.9% for ISTH sepsis-induced coagulopathy criteria, respectively.
Conclusion
Compared with conventional DIC scoring systems, a machine learning model might exhibit higher prediction accuracy.
{"title":"A machine learning model for early and accurate prediction of overt disseminated intravascular coagulation before its progression to an overt stage","authors":"","doi":"10.1016/j.rpth.2024.102519","DOIUrl":"10.1016/j.rpth.2024.102519","url":null,"abstract":"<div><h3>Background</h3><p>Recent studies suggested an expected survival benefit associated with anticoagulant therapies for sepsis in patients with disseminated intravascular coagulation (DIC). However, anticoagulant therapies for overt DIC are no longer assumed to regulate pathologic progression as overt DIC is a late-phase coagulation disorder. Therefore, methods for early prediction of sepsis-induced DIC before its progression to an overt stage are strongly required.</p></div><div><h3>Objectives</h3><p>We aimed to develop a prediction model for overt DIC using machine learning.</p></div><div><h3>Methods</h3><p>This retrospective, observational study included adult septic patients without overt DIC. The objective variable was binary classification of whether patients developed overt DIC based on International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. Explanatory variables were the baseline and time series data within 7 days from sepsis diagnosis. Light Gradient Boosted Machine method was used to construct the prediction model. For controls, we assessed sensitivity and specificity of Japanese Association for Acute Medicine DIC criteria and ISTH sepsis-induced coagulopathy criteria for subsequent onset of overt DIC.</p></div><div><h3>Results</h3><p>Among 912 patients with sepsis, 139 patients developed overt DIC within 7 days from diagnosis of sepsis. Sensitivity, specificity, and area under the receiver operating characteristic curve for predicting onset of overt DIC within 7 days were 84.4%, 87.5%, and 0.867 in the test cohort and 95.0%, 75.9%, and 0.851 in the validation cohort, respectively. Sensitivity and specificity by the diagnostic thresholds were 54.7% and 74.9% for Japanese Association for Acute Medicine DIC criteria and 63.3% and 71.9% for ISTH sepsis-induced coagulopathy criteria, respectively.</p></div><div><h3>Conclusion</h3><p>Compared with conventional DIC scoring systems, a machine learning model might exhibit higher prediction accuracy.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002140/pdfft?md5=d51093388511770de572857b6bc2dfd7&pid=1-s2.0-S2475037924002140-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962992","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102499
Coagulopathy continues to be a major challenge in the management of patients with acute promyelocytic leukemia (APL). Novel differentiating agents have led to improved survival in these patients, but perturbations in coagulation continue to have an impact on their prognosis. The most worrisome of coagulation disturbances is bleeding, which is not an uncommon cause of early death in APL. Despite this, there are no consistent predictors of this high risk of fatal hemorrhage in APL. In this context, the fibrinolytic system has been identified as a crucial role player in APL coagulopathy. However, the current guidelines for the management of APL give little regard to tests that measure the fibrinolytic system while giving more importance to close monitoring of conventional coagulation tests and platelet counts to identify the coagulopathy. More recently, viscoelastic tests have come to usefulness in determining global hemostasis and have been widely used for “diagnosing” hyperfibrinolysis in selected clinical settings. In this review, we attempt to describe risk assessment models for diagnosing APL coagulopathy, describe the possible application of viscoelastic tests in this setting, and persuade clinicians to reconsider the use of antifibrinolytics to improve survival of APL patients.
{"title":"Hemorrhage in acute promyelocytic leukemia—fibrinolysis in focus","authors":"","doi":"10.1016/j.rpth.2024.102499","DOIUrl":"10.1016/j.rpth.2024.102499","url":null,"abstract":"<div><p>Coagulopathy continues to be a major challenge in the management of patients with acute promyelocytic leukemia (APL). Novel differentiating agents have led to improved survival in these patients, but perturbations in coagulation continue to have an impact on their prognosis. The most worrisome of coagulation disturbances is bleeding, which is not an uncommon cause of early death in APL. Despite this, there are no consistent predictors of this high risk of fatal hemorrhage in APL. In this context, the fibrinolytic system has been identified as a crucial role player in APL coagulopathy. However, the current guidelines for the management of APL give little regard to tests that measure the fibrinolytic system while giving more importance to close monitoring of conventional coagulation tests and platelet counts to identify the coagulopathy. More recently, viscoelastic tests have come to usefulness in determining global hemostasis and have been widely used for “diagnosing” hyperfibrinolysis in selected clinical settings. In this review, we attempt to describe risk assessment models for diagnosing APL coagulopathy, describe the possible application of viscoelastic tests in this setting, and persuade clinicians to reconsider the use of antifibrinolytics to improve survival of APL patients.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924001948/pdfft?md5=c6e6781ca1995e33bc9c94de3ff17ba6&pid=1-s2.0-S2475037924001948-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141710439","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102538
{"title":"Navigating the inevitable: artificial intelligence and the future of scientific communication","authors":"","doi":"10.1016/j.rpth.2024.102538","DOIUrl":"10.1016/j.rpth.2024.102538","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002334/pdfft?md5=09d5d64a7dd5f10ee2286cf1caaeb157&pid=1-s2.0-S2475037924002334-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142040013","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102526
Background
Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non–COVID-19 CAP remains uncertain.
Objectives
To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non–COVID-19 CAP.
Methods
We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non–COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates.
Results
We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; I2 = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; I2 = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; I2 = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias.
Conclusion
In hospitalized patients with non–COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.
{"title":"The association of antiplatelet agents with mortality among patients with non–COVID-19 community-acquired pneumonia: a systematic review and meta-analysis","authors":"","doi":"10.1016/j.rpth.2024.102526","DOIUrl":"10.1016/j.rpth.2024.102526","url":null,"abstract":"<div><h3>Background</h3><p>Community-acquired pneumonia (CAP) triggers inflammatory and thrombotic host responses driving morbidity and mortality. Antiplatelet agents may favorably modulate these pathways; however, their role in non–COVID-19 CAP remains uncertain.</p></div><div><h3>Objectives</h3><p>To evaluate the association of antiplatelet agents with mortality in hospitalized patients with non–COVID-19 CAP.</p></div><div><h3>Methods</h3><p>We conducted a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) of adult patients hospitalized for non–COVID-19 CAP exposed to antiplatelet agents (acetylsalicylic acid or P2Y12 inhibitors). We searched MEDLINE, Embase, and CENTRAL from inception to August 2023. Our primary outcome was all-cause mortality: meta-analyzed (random-effects models) separately for observational studies and RCTs. For observational studies, we used adjusted mortality estimates.</p></div><div><h3>Results</h3><p>We included 13 observational studies (123,012 patients; 6 reported adjusted mortality estimates) and 2 RCTs (225 patients; both high risk of bias). In observational studies reporting hazard ratio, antiplatelet agents were associated with lower mortality (hazard ratio, 0.65; 95% CI, 0.46-0.91; <em>I</em><sup><em>2</em></sup> = 85%; 4 studies, 91,430 patients). In studies reporting adjusted odds ratio, antiplatelet agent exposure was associated with reduced odds of mortality (odds ratio, 0.67; 95% CI, 0.45-1.00; <em>I</em><sup><em>2</em></sup> = 0%; 2 studies, 24,889 patients). Among RCTs, there was a nonsignificant association with mortality (risk ratio, 0.66; 95% CI, 0.20-2.25; <em>I</em><sup><em>2</em></sup> = 54%; 2 studies, 225 patients). By the Grading of Recommendations, Assessment, Development, and Evaluation criteria, the certainty of the evidence was low, primarily due to risk of bias.</p></div><div><h3>Conclusion</h3><p>In hospitalized patients with non–COVID-19 CAP, antiplatelet agents may be associated with reduced mortality compared with usual care or placebo, but the certainty of evidence is low.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002218/pdfft?md5=80d9aa8c72ce7356def6af8450a2773d&pid=1-s2.0-S2475037924002218-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141845266","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 : 2024-07-01DOI: 10.1016/j.rpth.2024.102475
Background
Cancer increases the risk of venous thromboembolism, and glioblastoma is one of the cancer types with the highest risk of venous thromboembolism (10%-30%). Tumor-intrinsic features are believed to affect vascular permeability and hypercoagulability, but novel models are required to study the pathophysiological dynamics underlying cancer-associated thrombosis at the molecular level.
Objectives
We have developed a novel cancer-on-a-chip model to examine the effects of glioblastoma cells on the deregulation of blood coagulation.
Methods
This was accomplished by coculturing vessel-forming human umbilical vein endothelial cells with glioblastoma spheroids overexpressing tissue factor (TF), the initiator of coagulation (U251 lentivirus, LV-TF) or an LV-control (U251 LV-Ctrl) in an OrganoPlate Graft platform.
Results
Using a modified thrombin generation assay inside the cancer-on-a-chip, we found that U251 LV-Ctrl and U251 LV-TF spheroids promoted an increased procoagulant state in plasma, as was shown by a 3.1- and 7.0-fold increase in endogenous thrombin potential, respectively. Furthermore, the anticoagulant drug rivaroxaban and TF coagulation-blocking antibody 5G9 inhibited the activation of blood coagulation in U251 LV-TF spheroid-containing graft plates, as was shown by a reduced endogenous thrombin potential (4.0- and 4.4-fold, respectively).
Conclusion
With this study, we present a novel 3-dimensional cancer-on-a-chip model that has the potential to be used in the discovery of new anticoagulant drugs and identification of optimal anticoagulant strategies for glioblastoma and other cancer types.
{"title":"Modeling cancer-associated hypercoagulability using glioblastoma spheroids in microfluidic chips","authors":"","doi":"10.1016/j.rpth.2024.102475","DOIUrl":"10.1016/j.rpth.2024.102475","url":null,"abstract":"<div><h3>Background</h3><p>Cancer increases the risk of venous thromboembolism, and glioblastoma is one of the cancer types with the highest risk of venous thromboembolism (10%-30%). Tumor-intrinsic features are believed to affect vascular permeability and hypercoagulability, but novel models are required to study the pathophysiological dynamics underlying cancer-associated thrombosis at the molecular level.</p></div><div><h3>Objectives</h3><p>We have developed a novel cancer-on-a-chip model to examine the effects of glioblastoma cells on the deregulation of blood coagulation.</p></div><div><h3>Methods</h3><p>This was accomplished by coculturing vessel-forming human umbilical vein endothelial cells with glioblastoma spheroids overexpressing tissue factor (TF), the initiator of coagulation (U251 lentivirus, LV-TF) or an LV-control (U251 LV-Ctrl) in an OrganoPlate Graft platform.</p></div><div><h3>Results</h3><p>Using a modified thrombin generation assay inside the cancer-on-a-chip, we found that U251 LV-Ctrl and U251 LV-TF spheroids promoted an increased procoagulant state in plasma, as was shown by a 3.1- and 7.0-fold increase in endogenous thrombin potential, respectively. Furthermore, the anticoagulant drug rivaroxaban and TF coagulation-blocking antibody 5G9 inhibited the activation of blood coagulation in U251 LV-TF spheroid-containing graft plates, as was shown by a reduced endogenous thrombin potential (4.0- and 4.4-fold, respectively).</p></div><div><h3>Conclusion</h3><p>With this study, we present a novel 3-dimensional cancer-on-a-chip model that has the potential to be used in the discovery of new anticoagulant drugs and identification of optimal anticoagulant strategies for glioblastoma and other cancer types.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S247503792400164X/pdfft?md5=aa71ae78ea999702519b5b9ae4c59f2a&pid=1-s2.0-S247503792400164X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141623731","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}