Emmanuel J Favaloro, Leonardo Pasalic, Jennifer Curnow
{"title":"100 Years of von Willebrand Disease: The Journey to Contemporary Diagnostic Pathways-An Illustrative Case-Based Narrative Review.","authors":"Emmanuel J Favaloro, Leonardo Pasalic, Jennifer Curnow","doi":"10.1055/a-2834-5520","DOIUrl":"10.1055/a-2834-5520","url":null,"abstract":"<p><strong>Abstract: </strong>von Willebrand disease (VWD) is the most commonly inherited bleeding disorder, with a prevalence surpassing hemophilia A. Unfortunately, VWD may be variously underdiagnosed, overdiagnosed, or misdiagnosed, depending on the expertise of the managing clinician and testing laboratories. Diagnostic challenges are due to the heterogeneity of VWD and the complexities surrounding laboratory assessment, including reactive influences on VWF levels. At least six types of VWD can be identified, with these classified according to the functional defect and/or level of deficiency in the plasma protein von Willebrand factor (VWF). The VWF protein has several functions, most of which can be assessed by laboratory testing; however, this increases the diagnostic complexity, and clinicians/laboratory staff may not understand the differences in these tests and what they assess. Thus, a battery of laboratory tests is required to enable an effective diagnosis or exclusion of VWD, as well as its type classification. VWD was first identified in a young female patient by Erik von Willebrand in 1924, with a seminal publication on his findings appearing in the literature in 1926. This year, 2026, represents 100 years of VWD. We review some of the history of VWD, as well as outlining the contemporary diagnostic pathway for VWD, assisted by several illustrative case examples.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"908-926"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147514571","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}
{"title":"Measurement Uncertainty in the Hemostasis Laboratory.","authors":"Stephen MacDonald","doi":"10.1055/a-2723-9166","DOIUrl":"10.1055/a-2723-9166","url":null,"abstract":"<p><strong>Abstract: </strong>Clinical laboratory results are inherently uncertain. Variability arises when repeating measurements of the same sample under different conditions. Measurement uncertainty (MU) is a metrological framework that quantifies this variability, enabling clinical interpretation and comparison of results within and between patients. In hemostasis assays, MU describes uncertainty propagation across the entire traceability chain-from international standards to final patient results. The Guide to the Expression of Uncertainty of Measurement (GUM) offered a statistically rigorous but complex method for estimating MU, limiting its widespread adoption. A relatively recent technical specification (TS) from the International Standardization Organization (ISO; ISO/TS 20914:2019) introduced a top-down approach that balances rigor with operational feasibility, supporting ISO 15189 compliance. However, its applicability to specialist areas such as hemostasis has been questioned. Furthermore, despite improved understanding of calculation methods, international guidance recommends against reporting results, together with MU, directly to service users; instead, the laboratory is required to provide it upon request. This review explores the implementation of different approaches for MU in hemostasis laboratories.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"899-907"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318476","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}
Marc H M Thelen, Marith van Schrojenstein Lantman, Anne Stavelin, Tze Ping Loh
{"title":"Comments to the International Council for Standardization in Hematology Guidance for New Lot Verification of Coagulation Reagents, Calibrators, and Controls.","authors":"Marc H M Thelen, Marith van Schrojenstein Lantman, Anne Stavelin, Tze Ping Loh","doi":"10.1055/a-2572-1299","DOIUrl":"10.1055/a-2572-1299","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"996-998"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773308","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}
Emmanuel J Favaloro, Benjamin Reardon, Leonardo Pasalic
{"title":"Laboratory Monitoring and Measuring of Clinical Anticoagulants.","authors":"Emmanuel J Favaloro, Benjamin Reardon, Leonardo Pasalic","doi":"10.1055/a-2907-8841","DOIUrl":"10.1055/a-2907-8841","url":null,"abstract":"<p><strong>Abstract: </strong>Haemostasis reflects a balance between procoagulant and anticoagulant forces. A relative excess of procoagulant forces and/or a relative lack of anticoagulant forces can predispose individuals to an increased risk of thrombosis. Conversely, a relative lack of procoagulant forces and/or a relative excess of anticoagulant forces can predispose individuals to an increased risk of bleeding. It is possible in several clinical situations to mitigate bleeding risk using various approaches, including provision of procoagulant material; conversely, thrombosis risk can be mitigated by using various clinical anticoagulants. In some cases, such therapies require laboratory monitoring or measurements; in particular, therapy using anticoagulants may require laboratory measuring or monitoring to ensure adequate anticoagulation without over- or under-coagulating patients, and thereby reducing any treatment associated risk of bleeding or thrombosis. In this narrative review, we detail the various anticoagulants under current clinical use, as well as the tests or assays used to measure anticoagulant levels, or to monitor anticoagulant therapy.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"927-936"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437791","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}
{"title":"Laboratory Diagnostics for Thrombosis and Hemostasis Testing-Part V.","authors":"Kristi J Smock, Karen A Moffat","doi":"10.1055/a-2912-7667","DOIUrl":"https://doi.org/10.1055/a-2912-7667","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":"52 8","pages":"887-888"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246399","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}
{"title":"External Quality Assessment for Unfractionated Heparin Monitoring: An Update from Australasia/Asia-Pacific.","authors":"Emmanuel J Favaloro, Sandya Arunachalam, Leonardo Pasalic","doi":"10.1055/a-2779-0035","DOIUrl":"10.1055/a-2779-0035","url":null,"abstract":"<p><strong>Abstract: </strong>Unfractionated heparin (UFH) remains a major anticoagulant therapy applied within the acute hospital system. Due to intra- and interpatient variability, UFH monitoring needs to be applied to ensure patients remain free of thrombotic and bleeding complications at too low and too high an UFH level, respectively. Monitoring of UFH therapy is usually achieved using either an activated partial thromboplastin time (aPTT) or an anti-factor Xa (anti-Xa) method. The former is a clotting assay that evaluates both the anti-factor IIa (anti-IIa or anti-thrombin) and anti-Xa anticoagulant activity of UFH and the latter is a chromogenic assay that evaluates just the anti-Xa anticoagulant activity of UFH. The aPTT method is perhaps more widely utilized since aPTT testing is performed by all hemostasis laboratories performing routine coagulation tests. However, the aPTT method requires establishment of an aPTT UFH therapeutic range. The anti-Xa method is favored in larger hospital sites and by most experts and uses a standard UFH therapeutic range. We report findings for aPTT and anti-Xa testing for UFH monitoring in our geographic region using recent data (testing for the past 5 years; 2020-2024 inclusive) from the Royal College of Pathologists of Australasia Quality Assurance Program, an international external quality assessment (EQA) program, with over 110 enrolments for this EQA module. Four samples are assessed each year, with these comprising various levels of UFH. Good reproducibility was observed for duplicate samples sent in different surveys. Coefficient of variation (%) data revealed moderate variation for samples containing UFH (10-40% for anti-Xa; 10-25% for aPTT). Anti-Xa reagents containing dextran sulphate tended to yield higher anti-Xa values than those without. Interpretations regarding UFH levels being below, within, or above therapeutic levels were generally reported as expected, according to the level of UFH present in the sample, especially for anti-Xa testing.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"956-966"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828057","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}
{"title":"Seminars in Thrombosis and Hemostasis: 2025 Impact Factor, Most Highly Cited Papers, and Other Journal Metrics.","authors":"Emmanuel J Favaloro","doi":"10.1055/a-2910-6717","DOIUrl":"https://doi.org/10.1055/a-2910-6717","url":null,"abstract":"","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":"52 8","pages":"889-898"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149246388","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}
{"title":"External Quality Assessment for Low Molecular Weight Heparin Monitoring in the Australasia/Asia-Pacific Region.","authors":"Emmanuel J Favaloro, Sandya Arunachalam, Leonardo Pasalic","doi":"10.1055/a-2900-7026","DOIUrl":"10.1055/a-2900-7026","url":null,"abstract":"<p><strong>Abstract: </strong>Low molecular weight heparin (LMWH) remains a widely utilized parenteral anticoagulant in hospital and outpatient settings for thromboprophylaxis and treatment of venous thromboembolism. While LMWH typically does not require routine monitoring due to predictable pharmacokinetics, anti-factor Xa (anti-Xa) monitoring is indicated in specific populations, including those with renal impairment, extremes of body weight, pregnancy, or unexplained treatment failure. LMWH monitoring relies exclusively on chromogenic anti-Xa assays, as LMWH's predominant anti-Xa activity with minimal anti-IIa effect renders activated partial thromboplastin time insensitive. Therapeutic targets are context-dependent: peak anti-Xa levels of 0.5 to 1.2 U/mL for twice-daily therapeutic dosing or 1.0 to 2.0 U/mL for once-daily dosing, measured 3- to 5-hour postdose. We report external quality assessment findings for anti-Xa testing of LMWH from the past 6 years (2020-2025 inclusive) using RCPAQAP (Royal College of Pathologists of Australasia Quality Assurance Program) data, an international program with approximately 150 laboratory enrolments. Four samples are assessed annually at varied LMWH concentrations (0, 0.2-0.3, 0.5-0.6, 0.8-1.0 U/mL). Good reproducibility was demonstrated for duplicate samples across surveys. Coefficient of variation data revealed moderate variability (10-25%) for detectable LMWH levels, lower than unfractionated heparin (UFH) monitoring variability. Method-related differences were observed, with Siemens Innovance anti-Xa assays yielding slightly higher values than Werfen HemosIL or Stago STA assays. Participant interpretations of LMWH levels (below/within/above therapeutic range) showed greater variability than UFH due to multiple valid therapeutic ranges for LMWH depending on dosing context. Overall, laboratories demonstrated acceptable analytical and interpretative performance for LMWH monitoring, which should provide some reassurance to both patients and their clinical carers.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"967-974"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382640","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}
Eric Salazar, Kristi J Smock, Taryn Cazzolli, Jeffrey S Dlott, Nathan Lickteig, Thomas A Long, Joseph J Mulvey, Morayma R Gil, Marian Rollins-Raval, Jun Teruya, Oksana Volod, Chance A Walker, Geoffrey D Wool, Nicole D Zantek, Andrew J Goodwin Iv
{"title":"D-Dimer Reporting and Harmonization: Analysis of College of American Pathologists D-Dimer Proficiency Testing Program.","authors":"Eric Salazar, Kristi J Smock, Taryn Cazzolli, Jeffrey S Dlott, Nathan Lickteig, Thomas A Long, Joseph J Mulvey, Morayma R Gil, Marian Rollins-Raval, Jun Teruya, Oksana Volod, Chance A Walker, Geoffrey D Wool, Nicole D Zantek, Andrew J Goodwin Iv","doi":"10.1055/a-2803-3165","DOIUrl":"10.1055/a-2803-3165","url":null,"abstract":"<p><strong>Abstract: </strong>Measurement of D-dimer, a fibrin degradation product, is crucial for diagnosing thrombotic and fibrinolytic conditions. Despite its expanding utility, D-dimer testing faces challenges due to varying assay methodologies and nonstandardized reporting. To understand D-dimer reporting practices, the College of American Pathologists Hemostasis and Thrombosis Committee analyzed proficiency testing data from D-dimer surveys conducted between 2020 and 2023 across multiple laboratories. The data demonstrate that laboratories commonly report units that differ from the assay package insert when reporting their proficiency testing results. We sought to assess variability in reporting practices and opportunities for improvement in D-dimer reporting amongst participants. To accomplish this, we harmonized all D-dimer results to ng/mL fibrinogen equivalent units from one distributed sample and assessed distinct populations of entries per instrument/reagent combination. Notable trends emerged from this analysis. Data from laboratories using the same instrument/reagent combinations clustered around different means, suggesting issues with unit reporting and/or conversion. Entries reported in mg/L or ug/mL D-dimer units commonly exhibited significant deviations from the dominant population. For one instrument/reagent combination, most reported values differed by approximately twice the certificate of analysis value. This analysis highlights potential issues with D-dimer reporting in proficiency testing. Whether these issues translate into issues with clinical D-dimer reporting requires further study.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"975-981"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132817","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}
{"title":"Transitioning of Patients from Direct-Acting Oral Anticoagulant to Heparin: Impact on Laboratory Testing.","authors":"Deepa J Arachchillage, Saravanan Vinayagam, Annie Parsons, Nilanthi Karawitage, Mike Laffan","doi":"10.1055/a-2734-2293","DOIUrl":"10.1055/a-2734-2293","url":null,"abstract":"<p><strong>Abstract: </strong>Direct oral anticoagulants (DOACs), including direct thrombin inhibitors (dabigatran) and direct factor Xa inhibitors (apixaban, rivaroxaban, edoxaban), have transformed anticoagulant management in recent years due to their predictable pharmacodynamics, rapid onset of action, and fixed dosing without the need for routine laboratory monitoring. Unfractionated heparin (UFH) remains the anticoagulant of choice for patients who are acutely unwell and treated in intensive care units due to its short half-life, reversibility, ease of dose titration, and nonrenal dependent excretion. It is therefore not uncommon for an individual's anticoagulation management to require rapid changing from DOAC to UFH. Due to UFH's complex pharmacokinetics, including nonspecific binding to acute phase proteins and dose-dependent clearance, careful laboratory monitoring, generally with activated partial thromboplastin time (APTT) or anti-factor Xa (anti-Xa) activity, is necessary. When transitioning from a DOAC to UFH, overlapping pharmacologic effects can significantly interfere with coagulation assays, particularly if residual DOAC levels persist at the time UFH is initiated. DOACs can prolong the APTT and elevate anti-Xa activity, leading to overestimation of UFH activity, inappropriate dose adjustments, and increased risk of bleeding or thromboembolic events. Here, we examine the laboratory implications of transitioning from DOAC therapy to UFH, with a focus on the performance and interpretation of APTT and anti-Xa assays in the presence of residual DOAC levels and how to overcome the interference of DOAC in UFH monitoring. We suggest an algorithm to follow during this transition.</p>","PeriodicalId":21673,"journal":{"name":"Seminars in thrombosis and hemostasis","volume":" ","pages":"982-990"},"PeriodicalIF":4.2,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145513666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}