Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Exploratory rivaroxaban trial for isolated calf deep vein thrombosis with a risk factor of thrombosis extension: an open-label, multicenter, randomized controlled trial","authors":"","doi":"10.1016/j.rpth.2024.102515","DOIUrl":"10.1016/j.rpth.2024.102515","url":null,"abstract":"<div><h3>Background</h3><p>Limited evidence exists regarding the incidence of recurrent venous thromboembolism (VTE) in patients diagnosed with isolated distal deep vein thrombosis (DVT) who are at risk of thrombosis extension whether they receive anticoagulation therapy or not.</p></div><div><h3>Objectives</h3><p>The study aimed to investigate the incidence of recurrent VTE and the impact of rivaroxaban in this patient population.</p></div><div><h3>Methods</h3><p>This open-label, exploratory, and randomized controlled trial was conducted at 7 centers in Japan between April 2019 and April 2022. Adult patients with isolated distal DVT at risk of thrombosis extension received either rivaroxaban combined with physical therapy or physical therapy alone for 90 days. Whole-leg ultrasound was performed at 14 and 90 days. We assessed a composite outcome of symptomatic or asymptomatic proximal DVT or symptomatic pulmonary embolism as the primary outcome until the end of the treatment period using an intention-to-treat analysis. Major bleeding was evaluated as a key secondary outcome.</p></div><div><h3>Results</h3><p>Out of 90 enrolled patients, 3 were excluded due to withdrawal of consent; therefore, we analyzed 87 participants. The rivaroxaban group (<em>n</em> = 42) reported no primary outcomes (0%; 95% CI, 0.0%-8.4%), whereas the physical therapy group (<em>n</em> = 45) had 2 cases of symptomatic proximal DVT (4.4%; 95% CI, 0.5%-15.1%). Major bleeding events occurred in 4 patients in the rivaroxaban group (9.5%; 95% CI, 2.7%-22.6%), whereas no events occurred in the physical therapy group (0%; 95% CI, 0%-7.9%).</p></div><div><h3>Conclusion</h3><p>Preliminary data suggest that rivaroxaban may reduce the risk of VTE recurrence among this patient subset, albeit with an increased incidence of bleeding events.</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/S2475037924002103/pdfft?md5=08d54b0330e6ca9b0791899a0db535c7&pid=1-s2.0-S2475037924002103-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690000","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":"Thromboembolic events in severe postpartum hemorrhage treated with recombinant activated factor VII: a systematic literature review and meta-analysis","authors":"","doi":"10.1016/j.rpth.2024.102533","DOIUrl":"10.1016/j.rpth.2024.102533","url":null,"abstract":"<div><p>Postpartum hemorrhage (PPH) is an obstetric complication with high associated morbidity. Recombinant activated factor VII (rFVIIa) is used to treat severe PPH when uterotonics fail to stop bleeding. However, data on the safety of rFVIIa treatment of severe PPH from adequately powered trials are lacking. We systematically reviewed published data on the incidence of thromboembolic events (TEs) in women with PPH treated or not treated with rFVIIa (PROSPERO CRD42022360736). Databases (Embase, MEDLINE, BIOSIS, Current Contents, and the Cochrane Library) were searched for peer-reviewed publications published between January 1996 and August 2022 and conference abstracts published between January 2017 and August 2022 using search terms related to thromboembolism or infarction and PPH. Data were extracted from all publications reporting on a general population of women with PPH with information on TEs. Descriptive summary statistics and the estimated proportion of TEs were analyzed using a generalized linear mixed model based on the binomial distribution. Quality assessments were based on the checklist by Downs and Black. From 1637 potentially eligible studies, 55 publications were included reporting on 611 women treated and 32,488 women not treated with rFVIIa. The global estimated proportion of TEs was 1.82% (prediction interval [PI], 0.30-10.23) and 0.72% (PI, 0.03-16.47) in women with severe PPH treated and those not treated with rFVIIa, respectively. The estimated proportions of TEs were similarly small, with wide and largely overlapping PIs. Additional well-designed trials are needed to improve understanding of TE incidence in PPH.</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/S2475037924002280/pdfft?md5=be0da4bab78466826c5464518f53f215&pid=1-s2.0-S2475037924002280-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141849860","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":"Spontaneous bleeding in chronic kidney disease: global coagulation assays may predict bleeding risk","authors":"","doi":"10.1016/j.rpth.2024.102520","DOIUrl":"10.1016/j.rpth.2024.102520","url":null,"abstract":"<div><h3>Background</h3><p>Chronic kidney disease (CKD) is associated with increased bleeding and thrombotic risks. Standard blood tests do not sufficiently quantify these risks. Global coagulation assays (GCAs) provide a more comprehensive assessment of coagulation.</p></div><div><h3>Objectives</h3><p>We aimed to evaluate if GCAs are predictive of spontaneous major bleeding (sMB) in CKD.</p></div><div><h3>Methods</h3><p>Adult patients with CKD (estimated glomerular filtration rate, &lt;30 mL/min/1.73m²) were recruited to this pilot prospective observational study. Testing with GCAs (thromboelastography, overall hemostatic potential, calibrated automated thrombogram, and plasminogen activator inhibitor-1) was performed, and the results were correlated to sMB events.</p></div><div><h3>Results</h3><p>Eighty-seven CKD patients (median age, 67 years; 67.8% male) were included, with median follow-up of 3.1 years. CKD patients demonstrated elevated fibrinogen, factor VIII, and von Willebrand factor antigen levels, while other conventional coagulation test results were within reference intervals. Ten episodes of sMB (11.5%) were captured (3.0/100 person-years), with no significant association demonstrated between sMB and antiplatelet use (<em>P</em> = .36), platelet count (<em>P</em> = .14), or renal function (urea, <em>P</em> = .27; estimated glomerular filtration rate, <em>P</em> = .09). CKD patients with sMB had more hypocoagulable GCA parameters compared with those without sMB. The lowest quartiles of endogenous thrombin potential (subhazard ratio [sHR], 7.11; 95% CI, 1.84-27.45), overall hemostatic potential (sHR, 6.81; 95% CI, 1.77-26.16), and plasminogen activator inhibitor-1 (sHR, 5.26; 95% CI, 1.55-17.91) were associated with sMB.</p></div><div><h3>Conclusion</h3><p>This pilot study demonstrates that GCAs such as thrombin and fibrin generation may predict sMB risk in patients with CKD, which has potential to be practice-changing. Larger studies are required to validate these findings.</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/S2475037924002152/pdfft?md5=ff2aea45562ef749471de4163fc80ab0&pid=1-s2.0-S2475037924002152-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851634","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":"Managing surgical relapse risk in acquired thrombotic thrombocytopenic purpura: a systematic review","authors":"","doi":"10.1016/j.rpth.2024.102478","DOIUrl":"10.1016/j.rpth.2024.102478","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/S2475037924001675/pdfft?md5=3920f44ea26e27f3ca81846026c365f0&pid=1-s2.0-S2475037924001675-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141630778","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":"Interference of lupus anticoagulant causing antiprothrombin and anti–beta-2-glycoprotein I antibodies on international normalized ratio measurements: comparative analysis of international normalized ratio methods","authors":"Rachel Gehlen ,&nbsp;Roxanne G. Moesbergen ,&nbsp;CuiCui Bai ,&nbsp;Philip G. de Groot ,&nbsp;A.J.Gerard Jansen ,&nbsp;Joost C.M. Meijers ,&nbsp;Bas de Laat ,&nbsp;Jasper A. Remijn","doi":"10.1016/j.rpth.2024.102470","DOIUrl":"10.1016/j.rpth.2024.102470","url":null,"abstract":"<div><h3>Background</h3><p>Life-long vitamin K antagonist (VKA) therapy is recommended as a standard of care in antiphospholipid syndrome (APS) patients with thrombosis. Concerns have been raised about the validity of international normalized ratio (INR) measurements in lupus anticoagulant (LA)-positive APS patients because LA may interfere with phospholipid-dependent coagulation tests and could elevate INR measurements.</p></div><div><h3>Objectives</h3><p>Here, we aimed to determine the interference of antigen-specific monoclonal and isolated patient antibodies with LA activity on INR measurements.</p></div><div><h3>Methods</h3><p>Pooled normal plasma and control plasma from patients on VKA (without LA) were incubated with monoclonal and isolated patient immunoglobulin G antiprothrombin and anti–beta-2-glycoprotein I antibodies that express LA activity. INR was determined before and after addition using 3 laboratory assays (Owren STA-Hepato Prest, Quick STA-NeoPTimal, and Quick STA-Neoplastine R) and 1 point-of-care test device (CoaguChek Pro II).</p></div><div><h3>Results</h3><p>Antiprothrombin and anti–beta-2-glycoprotein I antibodies with LA activity interfered with recombinant human thromboplastin reagents (Quick STA-Neoplastine R and CoaguChek Pro II), particularly when added to plasma of VKA-treated controls. This effect was most evident on point-of-care test INR measurements, while the recombinant Quick reagent exhibited a lesser degree of interference. In contrast, tissue-derived thromboplastin reagents (Owren STA-Hepato Prest and Quick STA-NeoPTimal) remained largely unaffected by these antibodies, both in pooled normal plasma and VKA anticoagulated control plasma. Among these reagents, the Owren INR reagent exhibited the lowest sensitivity to the influence of LA antibodies. This observed difference in sensitivity is independent of the plasma dilution factor or the presence of factor V or fibrinogen in Owren reagent.</p></div><div><h3>Conclusion</h3><p>INR reagents that utilize recombinant human thromboplastin are more sensitive to the presence of monoclonal and patient-derived antibodies with LA activity. Consequently, APS patients positive for LA should be monitored using tissue-derived thromboplastin reagents, given its reduced susceptibility to interference by LA-causing antibodies.</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/S2475037924001596/pdfft?md5=907440664fb64fd45bb59c757e8a972f&pid=1-s2.0-S2475037924001596-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141409482","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":"Real-world usage and effectiveness of recombinant factor VIII/factor IX Fc in hemophilia A/B: final data from the 24-month, prospective, noninterventional PREVENT study in Germany","authors":"","doi":"10.1016/j.rpth.2024.102482","DOIUrl":"10.1016/j.rpth.2024.102482","url":null,"abstract":"<div><h3>Background</h3><p>Real-world experience with efmoroctocog alfa (a recombinant factor [F]VIII Fc fusion protein [rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) is needed to bridge evidence gaps.</p></div><div><h3>Objectives</h3><p>To describe rFVIIIFc/rFIXFc usage and effectiveness over a 24-month prospective period.</p></div><div><h3>Methods</h3><p>PREVENT (NCT03055611), a noninterventional study across 25 German hemophilia treatment centers, enrolled previously treated persons with hemophilia A and B (all ages/severities) on individualized rFVIIIFc/rFIXFc prophylaxis before/at enrollment. Primary endpoints included annualized bleeding rate (ABR), injection frequency (IF), and factor consumption (FC). Additionally, up to 12 months of retrospective FVIII/FIX data were collected. Physician and patient satisfaction, and safety outcomes were also assessed.</p></div><div><h3>Results</h3><p>Overall, 150 patients received ≥1 rFVIIIFc dose and 47 patients received ≥1 rFIXFc dose, with median prospective follow-up of 20.6 and 21.0 months, respectively. rFVIIIFc/rFIXFc demonstrated low median ABR (0.5/1.7), annualized IF (121.8/52.2 injections/y), and FC (4611.7/2423.9 IU/kg) in line with product labels. Compared with previous FVIII/FIX, there was a 56.0% reduction in ABR for rFVIIIFc (rate ratio, 0.44; 95% CI, 0.31-0.64), with no change for rFIXFc (rate ratio, 0.93; 95% CI, 0.66-1.31); rFVIIIFc/rFIXFc reduced annualized IF (rFVIIIFc, mean difference, −31.7; 95% CI, −40.3 to −23.1; rFIXFc, mean difference, −37.3; 95% CI, −46.9 to −27.8), while FC remained stable (rFVIIIFc, +374.1; 95% CI, +46.8 to +701.3; rFIXFc, +503.9; 95% CI, +95.4 to +912.4). Most physicians and patients were satisfied or highly satisfied with rFVIIIFc/rFIXFc. rFVIIIFc/rFIXFc were well tolerated, with no inhibitor development or treatment-related serious adverse events.</p></div><div><h3>Conclusion</h3><p>Real-world PREVENT data complement phase 3 trials and show that individualized rFVIIIFc/rFIXFc prophylaxis provided stable bleed protection with low IF and maintained FC. Compared with previous FVIII, ABR was considerably reduced with rFVIIIFc, with stable annualized FC. For rFIXFc, bleed protection was maintained vs previous FIX while reducing annualized IF.</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/S2475037924001717/pdfft?md5=d34012183ee4054591d75ab52ad9d95b&pid=1-s2.0-S2475037924001717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141638879","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 in valvular heart disease: is von Willebrand factor the culprit?","authors":"","doi":"10.1016/j.rpth.2024.102506","DOIUrl":"10.1016/j.rpth.2024.102506","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/S2475037924002012/pdfft?md5=acd725b13f9cda641fb02327e62bfb3d&pid=1-s2.0-S2475037924002012-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141711684","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":"In vitro assessment of the risk of ABCB1-mediated drug–drug interaction between rivaroxaban and tacrolimus in human embryonic kidney 293 recombinant cell lines","authors":"","doi":"10.1016/j.rpth.2024.102521","DOIUrl":"10.1016/j.rpth.2024.102521","url":null,"abstract":"<div><h3>Background</h3><p>In lung transplant patients, direct oral anticoagulants are often taken in combination with immunosuppressive drugs such as tacrolimus. Since tacrolimus is a substrate and inhibitor of the efflux protein ABCB1, also transporting direct oral anticoagulants, a possible drug–drug interaction mediated by competition for this transporter needs to be investigated.</p></div><div><h3>Objectives</h3><p>To determine the <em>in vitro</em> effect of tacrolimus on ABCB1-mediated rivaroxaban transport in order to support clinician practice.</p></div><div><h3>Methods</h3><p>Recombinant cell line models, based on human embryonic kidney 293 cells, were generated by a stable transfection process to overexpress ABCB1 or not (control cells). The impact of tacrolimus on ABCB1-mediated rivaroxaban transport was assessed by accumulation experiments.</p></div><div><h3>Results</h3><p>ABCB1 expression decreased the cellular accumulation of rivaroxaban and tacrolimus at their respective clinically relevant concentrations when compared with control cells. This confirms the involvement of ABCB1 in the active transport of tacrolimus and rivaroxaban. However, tacrolimus had no significant influence on rivaroxaban disposition at those clinically relevant concentrations.</p></div><div><h3>Conclusion</h3><p>Our study does not provide evidence for a possible interaction between tacrolimus and rivaroxaban when used together in practice.</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/S2475037924002164/pdfft?md5=4bec598e07edbcc379d704c378e999c9&pid=1-s2.0-S2475037924002164-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141851468","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":"The association between unemployment and treatment among adults with hemophilia","authors":"","doi":"10.1016/j.rpth.2024.102514","DOIUrl":"10.1016/j.rpth.2024.102514","url":null,"abstract":"<div><h3>Background</h3><p>People with hemophilia often experience pain and suffer from comorbidities related to their bleeding disorder. Consequently, unemployment due to disability is prevalent among people with hemophilia.</p></div><div><h3>Objectives</h3><p>To explore associations between unemployment due to disability and treatment while adjusting for known risk factors for unemployment.</p></div><div><h3>Methods</h3><p>Collecting data from 20 hemophilia centers from 15 European countries, the Age-related DeVelopments ANd ComorbiditiEs in hemophilia study recruited 785 participants aged 40 years and over with hemophilia A or B. A comprehensive electronic case report form included items related to patient characteristics, demographic information, past and current treatment regimens, and medical history, including a lifelong history of comorbidities. Baseline data from the Age-related DeVelopments ANd ComorbiditiEs in hemophilia study was analyzed using descriptive statistics and logistic regression models.</p></div><div><h3>Results</h3><p>Employment status was available for 756 of 785 participants aged 40 to 88 years (median, 53 years). We used regression analysis to compare people with hemophilia who were fully employed with those who were unemployed due to disability. This analysis included 424 participants. Using multivariable logistic regression, we found that age (odds ratio [OR], 1.07; <em>P</em> &lt; .01), severe hemophilia (OR, 10.81; <em>P</em> &lt; .01), current smoker (OR, 2.53; <em>P</em> &lt; .01), and psychiatric disorder (OR, 4.18; <em>P</em> = .02) were associated with increased odds of unemployment due to disability. In contrast, prophylactic treatment (OR, 0.44; <em>P</em> = .01) was associated with decreased odds.</p></div><div><h3>Conclusion</h3><p>Our analysis suggests that by maintaining factor levels above a critical threshold (3%-5%), prophylactic treatment for people with hemophilia could help avoid unemployment due to disability. While prophylaxis is more costly and can be burdensome, the benefits to material well-being and quality of life could be substantial.</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/S2475037924002097/pdfft?md5=e507947a1148f3326b1e2389baf5325f&pid=1-s2.0-S2475037924002097-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141697838","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":"Caplacizumab improves clinical outcomes and is well tolerated across clinically relevant subgroups of patients with immune-mediated thrombotic thrombocytopenic purpura","authors":"","doi":"10.1016/j.rpth.2024.102512","DOIUrl":"10.1016/j.rpth.2024.102512","url":null,"abstract":"<div><h3>Background</h3><p>Immune-mediated thrombotic thrombocytopenic purpura (iTTP) may lead to microvascular thrombosis and mortality, despite patients receiving appropriate standard of care treatment (immunosuppressive therapy and therapeutic plasma exchange). Caplacizumab directly inhibits von Willebrand factor–platelet interaction and consequently prevents microthrombi formation.</p></div><div><h3>Objectives</h3><p>This study aimed to determine the efficacy and safety of caplacizumab in diverse, clinically relevant patient subgroups.</p></div><div><h3>Methods</h3><p>In this post hoc analysis of phase 3 HERCULES study (NCT02553317), patients were categorized by clinically relevant subgroups (prior iTTP history, iTTP severity at presentation, and initial immunosuppression regimen).</p></div><div><h3>Results</h3><p>In patients with previous acute iTTP episodes, less severe disease at presentation, or those who received a corticosteroid-only initial immunosuppression regimen, time to platelet count response was shorter with caplacizumab vs placebo. Across all subgroups, fewer patients experienced a composite outcome of iTTP-related death, exacerbation, or major thromboembolic event on caplacizumab vs placebo. Placebo-treated patients remained at risk of exacerbations and refractoriness on either initial immunosuppression regimen (ie, corticosteroids only or corticosteroids plus rituximab). In the corticosteroids plus rituximab group, no exacerbations were reported in caplacizumab-treated patients, but 8 of the 16 (50%) patients experienced exacerbations in the placebo group. Safety outcomes were consistent with the findings of the main HERCULES study.</p></div><div><h3>Conclusion</h3><p>Caplacizumab treatment of acute iTTP, in combination with therapeutic plasma exchange and immunosuppression, was safe and effective regardless of prior iTTP history, severity, or initial immunosuppression regimen and improved patient outcomes across clinically diverse subgroups. These findings emphasize the need for treatments with rapid onset of action that can reduce mortality and iTTP-related complications.</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/S2475037924002073/pdfft?md5=c6a35baa1171484690e576461bd88b75&pid=1-s2.0-S2475037924002073-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141702142","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}