Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"The influence of severity of hemophilia on bone mineral density and fracture risk","authors":"Pia Ransmann ,&nbsp;Jamil Hmida ,&nbsp;Marius Brühl ,&nbsp;Frank Alexander Schildberg ,&nbsp;Georg Goldmann ,&nbsp;Johannes Oldenburg ,&nbsp;Max Jaenisch ,&nbsp;Fabian Tomschi ,&nbsp;Thomas Hilberg ,&nbsp;Andreas Christian Strauss","doi":"10.1016/j.rpth.2024.102624","DOIUrl":"10.1016/j.rpth.2024.102624","url":null,"abstract":"<div><h3>Background</h3><div>Evidence states that persons with hemophilia are frequently affected by low bone mineral density (BMD). Data assessing the relationship between severity of hemophilia and occurrence of osteoporosis are lacking.</div></div><div><h3>Objectives</h3><div>This prospective cohort study aimed to assess the impact of hemophilia severity on BMD and to investigate trabecular bone score (TBS) and fracture risk (FRAX).</div></div><div><h3>Methods</h3><div>This prospective cohort study evaluated the BMD, TBS, and FRAX in 255 persons with hemophilia using dual x-ray absorptiometry. The International Society for Clinical Densitometry guidelines were used for classification: osteoporosis (T-score &lt;−2.5), osteopenia (T-score &lt;−1.0), normal (T-score &gt;−1.0). Patients younger than 50 years of age with a Z-score of &lt;−2.0 were considered below the expected range for age.</div></div><div><h3>Results</h3><div>Of 255 persons with hemophilia (mild: <em>n</em> = 52, moderate: <em>n</em> = 53, severe: <em>n</em> = 150) aged 43 ± 15 years (mean ± SD), 63.1% showed reduced BMD. Even 11.9% of persons with hemophilia aged &lt;50 years were classified as below the expected range for age. Neck BMD decreased linearly with severity (mild: 0.907 ± 0.229, moderate: 0.867 ± 0.131, severe: 0.799 ± 0.143; <em>P</em> = .01). TBS was classified as “normal” in <em>n</em> = 178 (81.3%) with a mean value of 1.403 ± 0.136, and there were no differences between severity levels (<em>P</em> = .54). The FRAX was 4.4% ± 3.0%. After adjustment of TBS, it was 2.8% ± 3.7%.</div></div><div><h3>Conclusion</h3><div>The present study shows that BMD is decreased in 63.1% of persons with hemophilia also depending on the severity of hemophilia. However, the largely normal TBS implies that the microarchitecture of the bone does not seem to be affected. It is recommended to include osteoporosis screening, including TBS analysis, in the comprehensive diagnostic work-up of persons with hemophilia, especially as they age.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102624"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748653","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}

{"title":"Dependence of clot structure and fibrinolysis on apixaban and clotting activator","authors":"Rebecca A. Risman ,&nbsp;Mitali Shroff ,&nbsp;Julie Goswami ,&nbsp;Valerie Tutwiler","doi":"10.1016/j.rpth.2024.102614","DOIUrl":"10.1016/j.rpth.2024.102614","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulants prevent the formation of potentially fatal blood clots. Apixaban is a direct oral anticoagulant that inhibits factor (F)Xa, thereby impeding the conversion of prothrombin into thrombin and the formation of blood clots. Blood clots are held together by fibrin networks that must be broken down (fibrinolysis) to restore blood flow. Fibrinolysis is initiated when tissue plasminogen activator (tPA) converts plasminogen to plasmin, which binds to and degrades a fibrin fiber. The effects of apixaban on clot structure and lysis have been incompletely studied.</div></div><div><h3>Objectives</h3><div>We aimed to study apixaban effects on clot structure, kinetics, and fibrinolysis using thrombin (low or high concentration) or tissue factor (TF) to activate clot formation.</div></div><div><h3>Methods</h3><div>We used a combination of confocal and scanning electron microscopy and turbidity to analyze the structure, formation kinetics, and susceptibility to lysis when plasma was activated with low concentrations of thrombin, high concentrations of thrombin, or TF in the presence or absence of apixaban.</div></div><div><h3>Results</h3><div>We found that the clotting activator and apixaban differentially modulated clot structure and lytic potential. Low thrombin clots with apixaban lysed quickly due to a loose network and FXa cleavage product’s cofactor with tPA; high thrombin clots lysed faster due to FXa cleavage product’s cofactor with tPA; TF generated loose clots with restricted lysis due to their activation of thrombin activatable fibrinolytic inhibitor.</div></div><div><h3>Conclusion</h3><div>Our study elucidates the role of apixaban in fibrinolytic pathways with different clotting activators and can be used for the development of therapeutic strategies using apixaban as a cofactor in fibrinolytic pathways.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"Article 102614"},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748650","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}

{"title":"Development and internal validation of a simple clinical score for the estimation of the probability of deep vein thrombosis in outpatient emergency department patients.","authors":"Thor-David Halstensen, Camilla Hardeland, Waleed Ghanima, Vigdis Abrahamsen Grøndahl, Aliaksandr Hubin, Mazdak Tavoly","doi":"10.1016/j.rpth.2024.102608","DOIUrl":"10.1016/j.rpth.2024.102608","url":null,"abstract":"<p><strong>Background: </strong>Wells score comprises subjective elements, making physicians reluctant to use Wells score or cause them to use it incorrectly.</p><p><strong>Objectives: </strong>To develop and internally validate a prediction score that is objective and simple for evaluating suspected deep vein thrombosis (DVT), with a safety comparable with that of Wells score.</p><p><strong>Methods: </strong>We performed a post hoc analysis using data from the Ri-Schedule study (NCT02486445) involving suspected DVT patients at Østfold Hospital's Emergency Department, Norway (2015-2018). Candidate variables were identified through bootstrapping technique, with a confirmed DVT diagnosis as the outcome variable. Sensitivity, specificity, negative predictive value (NPV), and positive predictive values (PPV) were estimated and compared with the 2-tier Wells score.</p><p><strong>Results: </strong>Among 1312 patients (median age, 64 years [IQR, 52-73]; 55% women), 19.9% were diagnosed with DVT. Exploration of 30 variables identified tenderness along deep veins and previous venous thromboembolism as significant predictors (selection frequency >60% in 1000 bootstrapping samples). The derived score categorized 450 patients with 0 items as unlikely to have DVT, of whom 8.0% were diagnosed with DVT, compared with 8.2% in DVT unlikely category according to Wells score. Compared with Wells score, the derived score demonstrated sensitivity of 86.2 (95% CI, 81.4-90.2) vs 80.1 (95% CI, 74.7-84.8), specificity of 39.4 (95% CI, 36.4-42.4) vs 55.3 (95% CI, 52.2-58.3), NPV of 92.0 (95% CI, 89.4-94.0) vs 91.8 (95% CI, 89.7-93.5), and PPV of 26.1 (95% CI, 24.8-27.5) vs 30.8 (95% CI, 28.9-32.8). When incorporating D-dimer cutoff of <0.5 µg/mL, the derived score had sensitivity of 99.6 (95% CI, 97.9-99.9), specificity of 16.1 (95% CI, 13.1-18.4), NPV of 99.4 (95% CI, 96.0-99.9), and PPV of 22.8 (95% CI, 22.3-23.3).</p><p><strong>Conclusion: </strong>The derived DVT score, with 2 objective variables, had a comparable safety with that of the Wells score. However, an external validation is mandated prior to clinical use.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"102608"},"PeriodicalIF":3.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882909","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}

{"title":"Complement-mediated hemolytic uremic syndrome associated with postpartum hemorrhage: case series and systematic review of individual participant data.","authors":"Anna Gurevich-Shapiro, Sharon Orbach-Zinger, Avi Leader, Galia Stemer, Arnon Wiznitzer, Pierre Singer, Miriam Davidovits, Michael Shapiro, Eva N Hamulyák, Pia Raanani, Galia Spectre","doi":"10.1016/j.rpth.2024.102579","DOIUrl":"10.1016/j.rpth.2024.102579","url":null,"abstract":"<p><strong>Background: </strong>Postpartum hemorrhage is considered a risk factor for pregnancy-associated complement-mediated hemolytic uremic syndrome (CM-HUS; previously known as atypical hemolytic uremic syndrome) but has not been systematically studied.</p><p><strong>Objectives: </strong>To systematically examine the role of postpartum hemorrhage in precipitating CM-HUS and to describe the characteristics of postpartum hemorrhage-associated CM-HUS, its prognosis and recommended management.</p><p><strong>Methods: </strong>A systematic review of individual participant data from case series and reports in addition to a case series from our institution. Search terms were \"thrombotic microangiopathy,\" \"atypical hemolytic uremic syndrome,\" and \"complement mediated\" combined with \"pregnancy,\" \"postpartum,\" and/or \"postpartum hemorrhage\". Cases of thrombotic microangiopathy other than CM-HUS were excluded. Outcomes were clinical and laboratory characteristics of postpartum hemorrhage-associated CM-HUS, treatment, and outcomes.</p><p><strong>Results: </strong>Thirty-three studies comprising 48 women with postpartum hemorrhage-associated CM-HUS and 3 patients from our institution were included in the study. Most women presented at term (28/45; 62%), delivered by cesarean section (21/41; 51%), and had pregnancy complications, mainly preeclampsia (16/51; 31%) or fetal demise (9/51; 18%). Hematological and renal abnormalities usually appeared within the first 24 hours postdelivery. The median platelet count was 46 × 10⁹/L (IQR, 26-72), and the median maximal lactate dehydrogenase was 2638 U/L (IQR, 1620-3588). Renal function normalized in 20/23 (87%) women treated with C5 inhibitors with or without plasma exchange; in 7/11 (63%) women treated with plasma exchange alone, but only in 3/17 (18%) patients treated with supportive care. Patients treated with C5 inhibitors and/or plasma exchange achieved significantly better renal outcomes compared with supportive care alone (<i>P</i> < .001).</p><p><strong>Conclusion: </strong>CM-HUS is a rare complication following postpartum hemorrhage and occurs mainly in women with preeclampsia and/or following cesarean section. Patients treated with C5 inhibitors and/or plasma exchange had a better renal prognosis compared with patients who received supportive treatment alone.</p>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 8","pages":"102579"},"PeriodicalIF":3.4,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11665619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882854","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}

{"title":"Efficacy and safety of hetrombopag in the treatment of recombinant human thrombopoietin–resistant thrombocytopenia after allogeneic hematopoietic stem cell transplantation","authors":"Jing Ni ,&nbsp;Jian Hong ,&nbsp;Xinglin Liang ,&nbsp;Jifei Dai ,&nbsp;Zhangbiao Long ,&nbsp;ChengXin Luan ,&nbsp;Mingzhen Yang ,&nbsp;Qingsheng Li","doi":"10.1016/j.rpth.2024.102578","DOIUrl":"10.1016/j.rpth.2024.102578","url":null,"abstract":"<div><h3>Background</h3><div>Thrombocytopenia after allogeneic hematopoietic cell transplantation is a challenging clinical problem. Recombinant human thrombopoietin (rhTPO) and thrombopoietin receptor agonists are increasingly used in posttransplant thrombocytopenia. However, the use of hetrombopag in patients with posttransplant thrombocytopenia, especially in patients with resistance to rhTPO, has not yet been reported.</div></div><div><h3>Objectives</h3><div>The present study aimed to investigate the efficacy and safety of hetrombopag in patients with rhTPO-resistant posttransplant thrombocytopenia.</div></div><div><h3>Methods</h3><div>This retrospective study included 21 patients with rhTPO-resistant posttransplant thrombocytopenia who received hetrombopag from August 2021 to July 2022. The primary endpoint was the overall response rate, including partial response and complete response (CR). We also evaluated the predictors of hetrombopag efficacy and adverse events.</div></div><div><h3>Results</h3><div>The overall response rate to hetrombopag was 81%, and the CR rate was 62%. The median time from hetrombopag initiation to response and CR were 16 and 31 days, respectively. Decreased megakaryocytes in bone marrow negatively correlated with CR to hetrombopag (<em>P</em> = .03). All the patients tolerated hetrombopag well without any significant increase in adverse events. At the last follow-up, 71% of responders had discontinued hetrombopag and sustained their best response.</div></div><div><h3>Conclusion</h3><div>Our results suggested that hetrombopag is an effective treatment option to promote platelet recovery in patients with posttransplant thrombocytopenia, even in patients resistant to rhTPO.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102578"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653653","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}

{"title":"Extracellular vesicle tissue factor and tissue factor pathway inhibitor are independent discriminators of sepsis-induced coagulopathy","authors":"Anna K. Tobiasch ,&nbsp;Georg F. Lehner ,&nbsp;Clemens Feistritzer ,&nbsp;Andreas Peer ,&nbsp;Birgit Zassler ,&nbsp;Viktoria M. Neumair ,&nbsp;Sebastian J. Klein ,&nbsp;Michael Joannidis","doi":"10.1016/j.rpth.2024.102596","DOIUrl":"10.1016/j.rpth.2024.102596","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis-induced disseminated intravascular coagulopathy (DIC) remains a challenging clinical entity associated with significant morbidity and mortality. Endothelial injury or activation and extracellular vesicles (EV) are postulated as important determinants of DIC.</div></div><div><h3>Objectives</h3><div>The aim of this study was to test the discriminatory ability of E-selectin, EV, tissue factor (TF) and TF pathway inhibitor (TFPI) in sepsis-induced coagulopathy.</div></div><div><h3>Methods</h3><div>In this prospective, single-center study, we collected plasma samples within 24 hours after sepsis diagnosis and followed these patients for 5 consecutive days. Overt DIC was determined by the International Society on Thrombosis and Haemostasis (ISTH) DIC score. Eighty-seven sepsis patients were recruited (35 with overt DIC) who presented with increased levels of EV, EV-associated TF procoagulant activity (TF-PCA), E-selectin, TF, and TFPI at admission compared with healthy subjects.</div></div><div><h3>Results</h3><div>Only TFPI levels and TF-PCA discriminated between sepsis patients with or without DIC (area under the curve = 0.76; <em>P</em> = .0002). Increased TF-PCA was not sensitive in detecting sepsis-associated DIC; however, levels above 1.38 pg/mL showed high specificity in this cohort (sensitivity 27%, specificity 95%). The hazard ratio to progress to DIC over 5 days was 1.14 (95% CI, 0.64-2.07) for TF-PCA levels of 0.5 pg/mL or higher and 3.18 (95% CI, 1.74-5.79) for TFPI levels of 22.28 ng/mL or higher at admission.</div></div><div><h3>Conclusion</h3><div>These findings highlight the pivotal roles of TF-PCA and TFPI in an early phase of sepsis-induced DIC. Only EV-associated and functionally active TF and not TF antigen levels showed a predictive potential regarding DIC. These novel results might support the improvement of diagnostic or even therapeutic strategies to mitigate the devastating consequences of DIC in septic patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102596"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654133","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}

{"title":"Enhanced thrombin and plasmin generation profiles in alpha-2-antiplasmin–deficient patients: Data from the Rare Bleeding disorders in the Netherlands study","authors":"Bauke Haisma ,&nbsp;Sanna R. Rijpma ,&nbsp;Marjon H. Cnossen ,&nbsp;Paul L. den Exter ,&nbsp;Ilmar C. Kruis ,&nbsp;Karina Meijer ,&nbsp;Laurens Nieuwenhuizen ,&nbsp;Nick van Es ,&nbsp;Roger E.G. Schutgens ,&nbsp;Nicole M.A. Blijlevens ,&nbsp;Waander L. van Heerde ,&nbsp;Saskia E.M. Schols","doi":"10.1016/j.rpth.2024.102604","DOIUrl":"10.1016/j.rpth.2024.102604","url":null,"abstract":"<div><h3>Background</h3><div>α2-Antiplasmin (A2AP) deficiency is a rare and often unidentified disorder characterized by increased fibrinolysis and subsequent bleeding. Global hemostasis assays may increase insight into the altered coagulation and fibrinolysis in these patients.</div></div><div><h3>Objectives</h3><div>To explore thrombin and plasmin generation profiles in A2AP-deficient patients, corresponding A2AP activity levels and associated bleeding phenotypes.</div></div><div><h3>Methods</h3><div>The Nijmegen hemostasis assay was used to assess thrombin and plasmin generation in 23 A2AP-deficient patients (median age, 50 years; 70% women) from the cross-sectional Rare Bleeding disorders in the Netherlands study. Analyzed parameters included thrombin peak height, thrombin potential, fibrin lysis time, plasmin peak height, plasmin velocity index, and plasmin potential. These parameters were expressed as percentages of a reference obtained from 37 healthy controls (median age, 46 years; 57% women). The Nijmegen hemostasis assay data were correlated with A2AP activity levels and International Society on Thrombosis and Hemostasis Bleeding Assessment Tool scores using Pearson correlation coefficients.</div></div><div><h3>Results</h3><div>Patients’ A2AP activity levels ranged from 23% to 83% (reference range, 89%-122%). Plasmin generation increased, as evidenced by significantly shorter fibrin lysis times (73%; <em>P</em> &lt; .001) and higher plasmin peak heights (203%; <em>P</em> &lt; .001), plasmin velocity indices (302%; <em>P</em> &lt; .001) and plasmin potentials (154%; <em>P</em> &lt; .001) in A2AP-deficient patients than those in healthy controls. Moreover, significantly higher thrombin potentials (146%; <em>P</em> &lt; .001) and thrombin peak heights (132%; <em>P</em> &lt; .001) were observed. Enhanced plasmin generation parameters showed statistically significant correlations with lower A2AP activity levels and higher International Society on Thrombosis and Hemostasis Bleeding Assessment Tool scores.</div></div><div><h3>Conclusion</h3><div>A2AP-deficient patients exhibited augmented plasmin generation profiles that correlated with A2AP activity level and bleeding phenotype. Interestingly, increased thrombin generation profiles were also found in these patients.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102604"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654128","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}

{"title":"Bleeding and quality of life in people with Glanzmann thrombasthenia—insights from the Glanzmann’s 360 study","authors":"Kate Khair,&nbsp;Simon Fletcher,&nbsp;Matthew Boyton,&nbsp;Michael Holland","doi":"10.1016/j.rpth.2024.102586","DOIUrl":"10.1016/j.rpth.2024.102586","url":null,"abstract":"<div><h3>Background</h3><div>Glanzmann thrombasthenia (GT) is a rare platelet function disorder that results in severe bleeding. We assessed clinical symptoms and psychological parameters to identify the unmet needs associated with GT.</div></div><div><h3>Objectives</h3><div>Glanzmann’s 360 is a mixed-methods study designed to give a contemporary snapshot of the impact of living with GT.</div></div><div><h3>Methods</h3><div>The study comprised a self-completion online survey complemented by interviews conducted with affected individuals and carers recruited via social media and hemophilia treatment centers.</div></div><div><h3>Results</h3><div>The survey was completed by 88 people with GT and 29 carers of children/young people with GT aged &lt;16 years. The population ranged in age from &lt;2 years to &gt;70 years; 56% were female. Although 47% had been diagnosed with GT under the age of 2 years, 12% were diagnosed after 20 years of age. For 82%, a bleeding phenotype was apparent by the age of 5 years. Most respondents (88%) had experienced at least one bleed in the past week. Bleeding disproportionally affected women. Bleeds resulted in frequent hospital contact and considerable psychological distress: 26% of the population had scores suggestive of low self-esteem, while 30% met criteria suggestive of symptomatic depression. Exploratory analyses suggest that bleed experiences are associated with impaired health-related quality of life.</div></div><div><h3>Conclusion</h3><div>The Glanzmann’s 360 study reveals the significant physical, psychosocial, and quality-of-life impairments that are likely to be linked to the frequent bleeds experienced by those with GT. Clinicians treating people with GT should promote access to multidisciplinary comprehensive care, including psychosocial support.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102586"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552330","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}

{"title":"Mechanistic insight into multiple antibody binding to ADAMTS13 in immune thrombotic thrombocytopenic purpura","authors":"Konstantine Halkidis ,&nbsp;Chan Meng ,&nbsp;Vikram G. Pillai ,&nbsp;Madison Shay ,&nbsp;Szumam Liu ,&nbsp;X. Long Zheng","doi":"10.1016/j.rpth.2024.102603","DOIUrl":"10.1016/j.rpth.2024.102603","url":null,"abstract":"<div><h3>Background</h3><div>Antibody-mediated inhibition of von Willebrand factor (VWF) cleavage by ADAMTS-13 results in immune thrombotic thrombocytopenic purpura (iTTP). However, the effects of multiple antibody binding to ADAMTS-13 are not fully understood.</div></div><div><h3>Objectives</h3><div>To determine how multiple antibodies affect ADAMTS13 activity under various conditions.</div></div><div><h3>Methods</h3><div>Single-chain fragments of the variable region isolated via phage display from patients with iTTP, FRETS-VWF73, native ADAMTS-13 in normal human plasma, and hydrogen-deuterium exchange plus mass spectrometry were used.</div></div><div><h3>Results</h3><div>We found that 2 stimulatory antibodies affect ADAMTS-13 turnover rate more than its substrate recognition. Hydrogen-deuterium exchange plus mass spectrometry revealed that 1 of these 2 stimulatory antibodies bound to the CUB2 domain that presumably interacts with the spacer domain of ADAMTS-13. Spacer domain is targeted by most inhibitory antibodies in iTTP. Both inhibitory and stimulating antibodies could bind ADAMTS-13 simultaneously but when both were present the inhibitory activity predominates. The antibody-mediated stimulation was lost, but the inhibition persisted when a modified substrate with the amino acid residue leucine at position 1603 of VWF was replaced by an alanine (VWF73-L1603A), interfering with active site binding.</div></div><div><h3>Conclusion</h3><div>These results support the hypothesis that the mechanism of action of both stimulatory and inhibitory anti-ADAMTS-13 antibodies in iTTP is through allosteric modification of the catalytic domain and that inhibition of ADAMTS-13 dominates when both are present. Our findings may provide a new avenue of exploration to develop targeted diagnostic and therapeutic approaches in the management of iTTP.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102603"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654129","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}

{"title":"Clinical features and treatment of 70 children with lupus anticoagulant-hypoprothrombinemia syndrome: a retrospective study from a single center in China","authors":"Dandan Tian ,&nbsp;Junfeng Zhang ,&nbsp;Jintu Lou ,&nbsp;Xuejun Chen ,&nbsp;Juan Liang ,&nbsp;Xiaojun Xu ,&nbsp;Hui Gao ,&nbsp;Wenjian Nie ,&nbsp;Qing Ye ,&nbsp;Hongqiang Shen","doi":"10.1016/j.rpth.2024.102577","DOIUrl":"10.1016/j.rpth.2024.102577","url":null,"abstract":"<div><h3>Background</h3><div>Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder characterized by the presence of lupus anticoagulant (LA) and acquired hypoprothrombinemia.</div></div><div><h3>Objectives</h3><div>To summarize the experience of diagnosis, clinical features, and treatment of lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS).</div></div><div><h3>Methods</h3><div>A retrospective study of 70 children diagnosed with LAHPS from January 2019 to February 2024 at a single center was conducted.</div></div><div><h3>Results</h3><div>A total of 70 subjects (32 boys and 38 girls), with a mean age of 5.58 years, were included in the study. Among these subjects, 15 had autoimmune diseases (AIDs), 51 had infections, and 4 had unknown causes. Fifty-six of 70 (80%) subjects experienced bleeding with the median bleeding score of 4, 1 of 70 (1.4%) presented with thrombosis, and 13 of 70 (18.6%) were asymptomatic. All patients exhibited prolonged prothrombin time, significantly prolonged activated partial thromboplastin time, decreased factor (F)II activity (FII:C), and positive lupus anticoagulant. There was a weak negative correlation between the severity of bleeding and FII:C level (<em>rs</em> = −0.4283; <em>P</em> &lt; .001). Patients with infection-associated LAHPS were younger than those with AIDs-associated LAHPS (<em>P</em> &lt; .0001). In the study, LAHPS subjects are treated with corticosteroids as the first-line therapy, or in combination with immunosuppressants. Coagulation factor replacement therapy can effectively prevent and control bleeding events. After follow-up, lupus anticoagulant of all patients had turned negative within 12 weeks. And, prothrombin time and FII:C were completely normalized of all patients without recurrence of bleeding and without thrombosis.</div></div><div><h3>Conclusion</h3><div>Children develop LAHPS most commonly after AIDs and infection. Most patients presented with mild to moderate bleeding. The severity of bleeding symptoms was not exactly parallel to the decreased FII:C level.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102577"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142445225","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}