{"title":"A novel automated chemiluminescent enzyme immunoassay for ADAMTS-13 activity enables accompanying measurements of the inhibitory autoantibodies","authors":"Masayuki Kubo , Kazuyasu Konko , Emi Kinoshita , Satoshi Uemae , Katsushi Kobayashi , Yoshinori Hayashi , Akihiko Kan , Yoshihiro Fujimura , Masanori Matsumoto","doi":"10.1016/j.jtha.2024.11.020","DOIUrl":"10.1016/j.jtha.2024.11.020","url":null,"abstract":"<div><h3>Background</h3><div>Thrombotic thrombocytopenic purpura (TTP) is a fatal disease caused by severe deficiency in ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs 13) activity. ADAMTS-13 activity measurement is essential for the diagnosis of TTP, but conventional standard assays are manual and time-consuming. Automated ADAMTS-13 activity assays have recently become available; however, their accuracy remains challenging.</div></div><div><h3>Objectives</h3><div>We here developed a novel chemiluminescent enzyme immunoassay (CLEIA) for ADAMTS-13 activity that is fully automated, highly sensitive, and has a short reaction time (17 minutes). We evaluated the utility of our fully automated CLEIA for measuring ADAMTS-13 activity and inhibitory antibodies and compared it with conventional manual assays.</div></div><div><h3>Methods</h3><div>We compared our CLEIA for ADAMTS-13 activity and inhibitory antibodies with an in-house FRETS-VWF73 assay and commercial enzyme-linked immunosorbent assay (ELISA) using samples from 100 patients and 50 healthy donors. Agreement between assays was evaluated using a cutoff value of 10 international units/dL for ADAMTS-13 activity and 0.5 Bethesda units/mL for inhibitory antibodies.</div></div><div><h3>Results</h3><div>The CLEIA and conventional assays for ADAMTS-13 activity correlated well. The CLEIA showed high agreement with the FRETS-VWF73 assay (kappa = 0.96) and ELISA (kappa = 1.0) in classifying patients with a cutoff value of 10 international units/dL for ADAMTS-13 activity. Furthermore, in classifying patients with the cutoff value of 0.5 Bethesda units/mL for inhibitory antibodies, the CLEIA agreed strongly with the FRETS-VWF73 assay (kappa = 0.95) and ELISA (kappa = 0.98). Its diagnostic performance for TTP was satisfactory.</div></div><div><h3>Conclusion</h3><div>The high-performance and fully automated CLEIA enables rapid in-hospital diagnosis and follow-up of TTP, as well as detection of inhibitory ADAMTS-13 autoantibodies.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 957-967"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813639","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}
Brittany Salter , Karen Moffat , Stephen Carlino , Jackie Dobson-Storr , Lee Beckett , Emma Broomhead , Liselotte Onelöv , Sarah Ge , Marina Atalla , Raymond Melika , Saumya Bansal , Steven Kitchen , Mark Crowther , Siraj Mithoowani
{"title":"Evaluation of the MRX PT DOAC assay for detection of clinically relevant factor Xa inhibitor drug levels","authors":"Brittany Salter , Karen Moffat , Stephen Carlino , Jackie Dobson-Storr , Lee Beckett , Emma Broomhead , Liselotte Onelöv , Sarah Ge , Marina Atalla , Raymond Melika , Saumya Bansal , Steven Kitchen , Mark Crowther , Siraj Mithoowani","doi":"10.1016/j.jtha.2024.12.005","DOIUrl":"10.1016/j.jtha.2024.12.005","url":null,"abstract":"<div><h3>Background</h3><div>Although routine monitoring is not needed for direct oral anticoagulants (DOACs), knowing if a clinically relevant DOAC level is present can be critical, especially in cases of severe bleeding or urgent surgery. Rapid assays to exclude these levels are necessary but not widely available.</div></div><div><h3>Objectives</h3><div>To determine the test performance of MRX PT DOAC for excluding clinically relevant DOAC drug levels.</div></div><div><h3>Methods</h3><div>The MRX PT DOAC (Nordic Biomarker, Umeå, Sweden) assay measures the functional effect of DOACs using the clot-time ratio, a ratio between DOAC-sensitive prothrombin time (PT) and DOAC-insensitive PT. We conducted a multicenter retrospective study of 152 samples from 151 patients with known DOAC levels to assess whether the MRX PT DOAC assay could exclude clinically relevant drug levels >50 ng/mL and whether test performance differed across coagulation analyzers. To assess generalizability, the assay was run on 4 coagulation analyzers: Werfen ACLTOP 750, Diagnostica Stago STACompact MAX, Sysmex CS2500, and Sysmex CN-6000.</div></div><div><h3>Results</h3><div>The MRX PT DOAC assay had a sensitivity of 100% with a CI of 70% to 100% and negative predictive value (NPV) of 100% (CI: 57%-100%) for edoxaban drug levels >50 ng/mL. For rivaroxaban, sensitivity was 100% (CI: 61%-100%) and NPV was 100% (CI: 5%-100%). For apixaban, sensitivity ranged from 59% to 83% (CI: 41%-93%) and NPV ranged from 0% to 50% (CI: 0%-69%). The specificity of the assay ranged from 61% to 86% (CI: 36%-97%) for apixaban, 36% to 50% (CI: 2%-97%) for edoxaban, and 75% to 100% (CI: 5%-100%) for rivaroxaban.</div></div><div><h3>Conclusion</h3><div>The MRX PT DOAC assay reliably excludes clinically relevant levels of edoxaban and rivaroxaban, but not apixaban, across multiple analyzers.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 989-996"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829152","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}
Jens Sundbøll , Katalin Veres , Frederikke S. Troelsen , Morten Würtz , Hans Erik Bøtker , Henrik Toft Sørensen
{"title":"Myocardial infarction and short- or long-term risk of a subsequent cancer diagnosis: a Danish Nationwide Cohort Study","authors":"Jens Sundbøll , Katalin Veres , Frederikke S. Troelsen , Morten Würtz , Hans Erik Bøtker , Henrik Toft Sørensen","doi":"10.1016/j.jtha.2024.12.008","DOIUrl":"10.1016/j.jtha.2024.12.008","url":null,"abstract":"<div><h3>Background</h3><div>Growing evidence suggests that myocardial infarction (MI) may be a marker of cancer risk, but many aspects of this relation are poorly understood.</div></div><div><h3>Objectives</h3><div>To examine the short- and long-term risk of incident cancer in patients presenting with MI.</div></div><div><h3>Methods</h3><div>Using nationwide population-based Danish health registries, we identified all patients with a first-time diagnosis of MI (1995-2021) and followed them for up to 28 years for any subsequent diagnosis of cancer. We computed risks and standardized incidence ratios with 95% CIs as the observed number of cancers relative to the expected number based on national cancer incidence rates by sex, age, and calendar year.</div></div><div><h3>Results</h3><div>Among 185 065 patients diagnosed with MI, we observed 25 315 subsequent cancers. The risk of any cancer was 2.4% after 1 year of follow-up, increasing to 25.8% after 28 years, taking the competing risks of death into account. During the first year of follow-up, the standardized incidence ratio of any cancer was 1.67 (95% CI, 1.62-1.73). The standardized incidence ratio remained moderately elevated during 2 to 5 years (1.03; 95% CI, 1.01-1.05) and beyond 5 years (1.07; 95% CI, 1.05-1.09). The strongest associations were found for hematological as well as obesity- and smoking-related cancers during the first year of follow-up, whereas primarily, the risk of smoking-related cancers remained elevated throughout the entire follow-up period.</div></div><div><h3>Conclusion</h3><div>MI was associated with subsequent risk of cancer, driven by hematologic, obesity-, and smoking-related cancers in the short term and smoking-related cancers in the long term.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 1023-1033"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864745","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}
Mohammed Abdullah Al Sharif , Brian Harnett , Subia Tasneem , Brian Leber , Christopher Hillis , Catherine P.M. Hayward
{"title":"“Discrepant low von Willebrand factor activity results on the ACL TOP analyzer are frequent in unselected patients with myeloproliferative neoplasms and show no correlation with high-molecular-weight multimer loss or bleeding phenotype”: comment from Al Sharif et al.","authors":"Mohammed Abdullah Al Sharif , Brian Harnett , Subia Tasneem , Brian Leber , Christopher Hillis , Catherine P.M. Hayward","doi":"10.1016/j.jtha.2024.11.017","DOIUrl":"10.1016/j.jtha.2024.11.017","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 1123-1126"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551814","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}
Ecaterina Scarlatescu , Jerrold H. Levy , Hunter Moore , Jecko Thachil , Toshiaki Iba , Lara N. Roberts , Ton Lisman
{"title":"Disseminated intravascular coagulation and cirrhotic coagulopathy: overlap and differences. The current state of knowledge. Communication from the SSC of the ISTH","authors":"Ecaterina Scarlatescu , Jerrold H. Levy , Hunter Moore , Jecko Thachil , Toshiaki Iba , Lara N. Roberts , Ton Lisman","doi":"10.1016/j.jtha.2024.11.019","DOIUrl":"10.1016/j.jtha.2024.11.019","url":null,"abstract":"<div><div>Patients with disseminated intravascular coagulation (DIC) have decreasing plasma levels of coagulation factors and platelet counts with increased levels of D-dimer. Standard laboratory tests are used clinically to diagnose DIC and quantify the severity of the disease. In patients with cirrhosis, liver-derived plasma coagulation factor levels are reduced due to decreased hepatic synthesis, further exacerbated by extravascular redistribution of these proteins, causing prolongation of routine diagnostic coagulation tests. Platelets are often decreased in cirrhosis due to reduced production and portal hypertension, resulting in hypersplenism and sequestration. Patients with cirrhosis frequently have elevated fibrin/fibrinogen degradation product levels without having acute medical decompensation. As a result, these patients commonly meet the laboratory criteria of DIC. However, it has been debated whether laboratory-assessed DIC is present in patients with cirrhosis and if it has clinical relevance. In this communication, we review hemostatic features in cirrhosis and DIC, examine published studies that evaluate the activation of hemostasis in patients with cirrhosis, and highlight future directions for research.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 1085-1106"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813641","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}
Kyle J. Comishen , Meha Bhatt , Katie Yeung , Jehan Irfan , Ayesha Zia , Robert F. Sidonio Jr. , Paula James
{"title":"Etiology and diagnosis of heavy menstrual bleeding among adolescent and adult patients: a systematic review and meta-analysis of the literature","authors":"Kyle J. Comishen , Meha Bhatt , Katie Yeung , Jehan Irfan , Ayesha Zia , Robert F. Sidonio Jr. , Paula James","doi":"10.1016/j.jtha.2024.11.014","DOIUrl":"10.1016/j.jtha.2024.11.014","url":null,"abstract":"<div><h3>Background</h3><div>Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with an individual’s quality of life. Many individuals with HMB are inadequately managed by health care providers.</div></div><div><h3>Objectives</h3><div>This systematic review aims to provide a comprehensive summary of the etiologies and diagnosis of HMB while calculating the prevalence of underlying causes among premenopausal patients and quantifying the test accuracy of diagnostic strategies.</div></div><div><h3>Methods</h3><div>MEDLINE, EMBASE, the Cochrane Library, and Web of Science were searched since inception to include studies investigating the prevalence of underlying etiology and diagnostic accuracy of investigations for HMB. The primary outcome was the prevalence of the causes of HMB, secondary outcome included the prevalence of etiology by age. Meta-analyses were conducted via random-effects model.</div></div><div><h3>Results</h3><div>In total, 53 studies were included. Forty-five studies included data on the prevalence of underlying HMB etiology, totaling 41 541 patients. The overall prevalence of bleeding disorders was 30% (95% CI, 14-46); von Willebrand disease, 8% (95% CI, 7-10); platelet function defect, 9% (95% CI, 7-12); abnormal thyroid, 3% (95% CI, 0-6); and polycystic ovarian syndrome, 8% (95% CI, 4-12). Subgroup analysis showed bleeding disorders were prevalent in 16% (95% CI, −8 to 41) of adults with HMB but in 39% (95% CI 18-60) of adolescents with HMB.</div></div><div><h3>Conclusion</h3><div>Many diagnoses were associated with bleeding disorders and, therefore, warrant investigation when assessing a patient with HMB of unknown etiology. The causes are likely age dependent and should be considered when diagnosing HMB.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 863-876"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770199","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}
Jori E. May , Arthur L. Allen , Bethany T. Samuelson Bannow , Carlee O’Connor , Katelyn W. Sylvester , Scott Kaatz
{"title":"Safe and effective anticoagulation use: case studies in anticoagulation stewardship","authors":"Jori E. May , Arthur L. Allen , Bethany T. Samuelson Bannow , Carlee O’Connor , Katelyn W. Sylvester , Scott Kaatz","doi":"10.1016/j.jtha.2024.11.024","DOIUrl":"10.1016/j.jtha.2024.11.024","url":null,"abstract":"<div><div>Anticoagulant use is prevalent and associated with significant potential for harm. Anticoagulation stewardship practice has emerged to address care gaps and promote safe, effective, and cost-conscious anticoagulation use across health care systems. We present 4 patient cases describing common challenges in anticoagulation management: inappropriate dosing of direct oral anticoagulants, the diagnosis and management of heparin-induced thrombocytopenia, periprocedural anticoagulation management, and heavy menstrual bleeding on anticoagulation. We discuss available examples of successful stewardship programs that can address the challenges of each case, demonstrating how an investment in anticoagulation stewardship can improve patient outcomes.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 779-789"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818466","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}
Anita Pirabe , Waltraud C. Schrottmaier , Dino Mehic , Hubert Hackl , Sabine Frühwirth , Anna Schmuckenschlager , Sarah Beck , Johanna Gebhart , Karoline Gleixner , Wolfgang Sperr , Alice Assinger
{"title":"Impaired hemostatic and immune functions of platelets after acute thrombocytopenia","authors":"Anita Pirabe , Waltraud C. Schrottmaier , Dino Mehic , Hubert Hackl , Sabine Frühwirth , Anna Schmuckenschlager , Sarah Beck , Johanna Gebhart , Karoline Gleixner , Wolfgang Sperr , Alice Assinger","doi":"10.1016/j.jtha.2024.11.029","DOIUrl":"10.1016/j.jtha.2024.11.029","url":null,"abstract":"<div><h3>Background</h3><div>Platelets are pivotal in maintaining vascular integrity, hemostasis, and immune modulation, with newly generated, immature platelets being the most responsive in fulfilling these tasks. Therefore, the immature platelet fraction provides insights into thrombopoiesis dynamics and clinical prognostication. However, it is currently unclear how immature platelet functions change in settings of acute thrombocytopenia.</div></div><div><h3>Objectives</h3><div>We aimed to investigate the functional consequences of acute thrombocytopenia on newly generated immature platelets in various mouse models and human subjects.</div></div><div><h3>Methods</h3><div>To examine platelet functionality after acute thrombocytopenia, we depleted either megakaryocytes using a platelet factor 4-specific inducible diphtheria toxin receptor transgenic mouse model or platelets via antibody-mediated depletion in mice, and collected blood from acute myeloid leukemia (AML) patients before and after consolidation or induction chemotherapy. Chemotherapy treatment was further repeated in an animal model. We assessed surface receptor expression of activation markers (CD62P, active GPIIb/IIIa, CD40L, CD63, CD107a) and toll-like receptors (TLR2, TLR4, TLR9) on immature and mature platelets following activation. Additionally, we investigated procoagulant platelet formation and platelet–leukocyte interactions in mouse models and patients with AML.</div></div><div><h3>Results</h3><div>In murine models, acute thrombocytopenia led to impaired hemostatic function and altered surface receptor expression in newly generated immature platelets. Similarly, AML patients during regeneration post chemotherapy exhibited reduced platelet activation and procoagulant function, alongside altered receptor expression and diminished platelet–leukocyte interactions.</div></div><div><h3>Conclusion</h3><div>After acute thrombocytopenia platelet-mediated hemostasis and immune modulation by newly generated platelets are impaired, underscoring the clinical relevance of understanding platelet function alterations in (post)thrombocytopenic conditions for therapeutic optimization.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 1052-1065"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829153","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}
Dasheng Luo , Liujie Zheng , Mingyang Ding , Defu Yu , Tao Chen , Ke Zheng , Juehua Jing , Yunfeng Yao
{"title":"Metalloproteomic analysis of hemophilic arthropathy synovial tissue: insights into metal overload and pathogenesis","authors":"Dasheng Luo , Liujie Zheng , Mingyang Ding , Defu Yu , Tao Chen , Ke Zheng , Juehua Jing , Yunfeng Yao","doi":"10.1016/j.jtha.2024.12.013","DOIUrl":"10.1016/j.jtha.2024.12.013","url":null,"abstract":"<div><h3>Background</h3><div>Hemophilic arthropathy (HA) is a joint disease characterized by local iron overload stemming from erythrocyte rupture and closely linked to synovial lesions. However, the precise molecular characteristics of clinical HA synovial samples remain to be defined.</div></div><div><h3>Objectives</h3><div>To gain insight into HA synovial tissue lesions, we utilized a metalloprotein strategy to compare the metal and protein spectra of HA with those of osteoarthritis and rheumatoid arthritis.</div></div><div><h3>Methods</h3><div>We collected synovial samples from patients with HA, osteoarthritis, and rheumatoid arthritis. Tissue metal and protein profiles were obtained by metallomics and proteomics, respectively. Finally, metalloproteomics strategies compared metal content, proteins, metalloproteins, and the life processes involved.</div></div><div><h3>Results</h3><div>Our metallomics analysis revealed an explicit increase in heavy metal content, particularly arsenic and mercury, in HA synovial samples. Through proteomics, we delineated specific metalloproteins and identified correlations between metals and pathways.</div></div><div><h3>Conclusion</h3><div>These findings yield valuable insights into the pathogenesis of HA and offer potential therapeutic targets for conditions characterized by iron overload.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 888-902"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142870846","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}
Michael Hack , Donald M. Arnold , Rumi Clare , Nikola Ivetic , Abirami Sudharshan , Hina Bhakta , Yi Zhang , John G. Kelton , Ishac Nazy
{"title":"Anti–platelet factor 4 antibody class and subclass in patients with vaccine-induced immune thrombocytopenia and thrombosis","authors":"Michael Hack , Donald M. Arnold , Rumi Clare , Nikola Ivetic , Abirami Sudharshan , Hina Bhakta , Yi Zhang , John G. Kelton , Ishac Nazy","doi":"10.1016/j.jtha.2024.12.017","DOIUrl":"10.1016/j.jtha.2024.12.017","url":null,"abstract":"<div><h3>Background</h3><div>Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare complication of adenoviral vector–based SARS-CoV-2 vaccines caused by platelet-activating anti–platelet factor 4 (PF4, CXCL4) antibodies. Despite similarities to heparin-induced thrombocytopenia (HIT), the humoral characteristics of VITT antibodies remain largely unknown.</div></div><div><h3>Objectives</h3><div>In this study, we described the distribution of antibody classes and subclasses in patients with VITT and compared the findings with those in published reports from patients with HIT.</div></div><div><h3>Methods</h3><div>We studied acute samples from patients diagnosed with VITT (<em>n</em> = 31) from Canada between March and July 2021. We quantified anti-PF4 antibody class and subclass distributions using an in-house anti-PF4 enzyme immunoassay. We then compared our results with clinical severity, such as time of symptom onset, platelet counts, and thrombosis.</div></div><div><h3>Results</h3><div>All VITT patients (<em>n</em> = 31) had anti-PF4 immunoglobulin G (IgG) antibodies. Of those, 16 (51.6%) also had immunoglobulin M and 5 (16.1%) also had immunoglobulin A. For anti-PF4 IgG subclasses, of the 31 VITT patients with IgG anti-PF4, 28 (90.3%) had IgG1, 20 (64.5%) had IgG2, 4 (12.9%) had IgG3, and 1 (3.2%) had IgG4. No significant correlations were observed between acute-phase clinical characteristics of VITT and different antibody distributions.</div></div><div><h3>Conclusion</h3><div>Anti-PF4 antibodies in VITT patients were predominantly IgG, particularly IgG1 and IgG2. Compared with published data on HIT, VITT antibodies were more often IgG2 and less frequently immunoglobulin A. The role of IgG1 and IgG2 anti-PF4 antibodies in VITT pathogenesis remains unknown, but our findings can improve our understanding of VITT immunology including its clinical presentations and aid in designing monoclonal antibodies to study anti-PF4 disorders further.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"23 3","pages":"Pages 1077-1084"},"PeriodicalIF":5.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143551877","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}