Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Letter in response to Bounaix et al. “Management of anticoagulation and factor XIII replacement in a patient with severe factor XIII deficiency and recurrent venous thromboembolic disease: case report and review of literature”","authors":"","doi":"10.1016/j.rpth.2024.102535","DOIUrl":"10.1016/j.rpth.2024.102535","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002309/pdfft?md5=d3045fb8c25860a06064eb3cc8d32f5a&pid=1-s2.0-S2475037924002309-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142098441","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":"Dual direct oral anticoagulant therapy in challenging thrombosis: a case series","authors":"","doi":"10.1016/j.rpth.2024.102546","DOIUrl":"10.1016/j.rpth.2024.102546","url":null,"abstract":"<div><h3>Background</h3><p>While anticoagulation therapy is highly effective at treating venous thromboembolism, some patients can develop rapidly progressive thrombosis in multiple organs or sites despite therapeutic anticoagulation. Effective strategies to manage life-threatening thrombosis in these patients are elusive.</p></div><div><h3>Objectives</h3><p>We describe our experience using dual direct oral anticoagulant (DOAC) therapy with a factor (F)Xa inhibitor (such as rivaroxaban or apixaban) and a FIIa inhibitor (dabigatran) for refractory cases of thrombosis.</p></div><div><h3>Methods</h3><p>A retrospective chart review of all patients treated with simultaneous dabigatran and an oral FXa inhibitor at our institution was conducted. We included all patients over the age of 18. The study was approved by the University of British Columbia Research Ethics Board (REB number: H23-02575).</p></div><div><h3>Results</h3><p>Eight patients were included. All patients initiated standard therapeutic anticoagulation upon diagnosis of acute venous thromboembolism with a median of 3 breakthrough thrombotic events prior to dual DOAC use. Five patients had a positive heparin-induced thrombocytopenia screen, but only 2 had heparin-induced thrombocytopenia confirmed on serotonin release assay testing. There were no recurrent deep vein thrombosis, pulmonary embolism, or bleeding events during dual DOAC use. Most patients ultimately transitioned to a single oral FXa inhibitor.</p></div><div><h3>Conclusion</h3><p>Dual DOAC therapy may be a useful strategy for managing challenging thrombosis cases resistant to conventional anticoagulation. Further research is warranted to validate these findings and explore the broader applicability of dual DOAC therapy in challenging thrombotic scenarios.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002413/pdfft?md5=816305b13c2dbee16632497e0e5e5dd9&pid=1-s2.0-S2475037924002413-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151132","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":"Antipolyphosphate monoclonal antibodies derived from autoimmune mice","authors":"","doi":"10.1016/j.rpth.2024.102550","DOIUrl":"10.1016/j.rpth.2024.102550","url":null,"abstract":"<div><h3>Background</h3><p>Inorganic polyphosphates (polyPs) are linear chains of phosphates that accelerate blood clotting. Targeting polyP <em>in vivo</em> has been shown to reduce thrombosis.</p></div><div><h3>Objectives</h3><p>To identify and characterize anti-polyP monoclonal antibodies that could be used as analytical tools and as antithrombotic agents.</p></div><div><h3>Methods</h3><p>Hybridomas were prepared from spleen cells from autoimmune NZBWF1/J female mice and screened for anti-polyP antibodies. Antibodies that bound polyP using enzyme-linked immunosorbent assay and pull-down assays were further characterized with plate binding, surface plasmon resonance, and plasma-based clotting assays. Antithrombotic potential was evaluated in a murine ferric chloride–induced carotid artery thrombosis model.</p></div><div><h3>Results</h3><p>Of 4 antibodies that bound polyP in our pull-down assay, 2 (PP2069 and PP2099) were available for further characterization. While analyzing these anti-polyP antibodies, we found secretory leukocyte peptidase inhibitor (SLPI) to be a common contaminant of these antibodies and that SLPI binds polyP. We removed SLPI quantitatively from our purified immunoglobulin G. Both PP2069 and PP2099 immunoglobulin G displayed high affinity for polyP but also bound to other polyanions such as DNA, heparin, and certain other glycosaminoglycans, indicating limited specificity. Both antibodies inhibited polyP-initiated plasma clotting <em>in vitro</em>. When tested <em>in vivo</em> in a mouse thrombosis model, however, neither PP2069 nor PP2099 exhibited a significant antithrombotic effect.</p></div><div><h3>Conclusion</h3><p>Autoimmune mice spontaneously produce antibodies against polyP. The 2 examples of anti-polyP monoclonal antibodies studied here not only bound to polyP with high affinity but also cross-reacted with DNA and heparin. Neither antibody protected against thrombosis in a mouse model, but they might have some utility for <em>in vitro</em> studies of polyP.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002450/pdfft?md5=f196d103a0baf733ec746abc85e4c216&pid=1-s2.0-S2475037924002450-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161862","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":"MYH9-related inherited thrombocytopenia: the genetic spectrum, underlying mechanisms, clinical phenotypes, diagnosis, and management approaches","authors":"","doi":"10.1016/j.rpth.2024.102552","DOIUrl":"10.1016/j.rpth.2024.102552","url":null,"abstract":"<div><p>Inherited thrombocytopenias have been considered exceedingly rare for a long time, but recent advances have facilitated diagnosis and greatly enabled the discovery of new causative genes. <em>MYH9</em>-related disease (<em>MYH9-</em>RD) represents one of the most frequent forms of inherited thrombocytopenia, usually presenting with nonspecific clinical manifestations, which renders it difficult to establish an accurate diagnosis. <em>MYH9-</em>RD is an autosomal dominant-inherited thrombocytopenia caused by deleterious variants in the <em>MYH9</em> gene encoding the heavy chain of nonmuscle myosin IIA. Patients with <em>MYH9</em>-RD usually present with thrombocytopenia and platelet macrocytosis at birth or in infancy, and most of them may develop one or more extrahematologic manifestations of progressive nephritis, sensorial hearing loss, presenile cataracts, and elevated liver enzymatic levels during childhood and adult life. Here, we have reviewed recent advances in the study of <em>MYH9</em>-RD, which aims to provide an updated and comprehensive summary of the current knowledge and improve our understanding of the genetic spectrum, underlying mechanisms, clinical phenotypes, diagnosis, and management approaches of this rare disease. Importantly, our goal is to enable physicians to better understand this rare disease and highlight the critical role of genetic etiologic analysis in ensuring accurate diagnosis, clinical management, and genetic counseling while avoiding ineffective and potentially harmful therapies for <em>MYH9</em>-RD patients.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002474/pdfft?md5=25f8cdaec23ba07ea71ddb4dc9a6f91c&pid=1-s2.0-S2475037924002474-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161861","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":"Oxidative stress–induced fibrinogen modifications in liver transplant recipients: unraveling a novel potential mechanism for cardiovascular risk","authors":"","doi":"10.1016/j.rpth.2024.102555","DOIUrl":"10.1016/j.rpth.2024.102555","url":null,"abstract":"<div><h3>Background</h3><p>Cardiovascular events represent a major cause of non–graft-related death after liver transplant. Evidence suggest that chronic inflammation associated with a remarkable oxidative stress in the presence of endothelial dysfunction and procoagulant environment plays a major role in the promotion of thrombosis. However, the underlying molecular mechanisms are not completely understood.</p></div><div><h3>Objectives</h3><p>In order to elucidate the mechanisms of posttransplant thrombosis, the aim of the present study was to investigate the role of oxidation-induced structural and functional fibrinogen modifications in liver transplant recipients.</p></div><div><h3>Methods</h3><p>A case-control study was conducted on 40 clinically stable liver transplant recipients and 40 age-matched, sex-matched, and risk factor–matched controls. Leukocyte reactive oxygen species (ROS) production, lipid peroxidation, glutathione content, plasma antioxidant capacity, fibrinogen oxidation, and fibrinogen structural and functional features were compared between patients and controls.</p></div><div><h3>Results</h3><p>Patients displayed enhanced leukocyte ROS production and an increased plasma lipid peroxidation with a reduced total antioxidant capacity compared with controls. This systemic oxidative stress was associated with fibrinogen oxidation with fibrinogen structural alterations. Thrombin-catalyzed fibrin polymerization and fibrin resistance to plasmin-induced lysis were significantly altered in patients compared with controls. Moreover, steatotic graft and smoking habit were associated with high fibrin degradation rate.</p></div><div><h3>Conclusion</h3><p>ROS-induced fibrinogen structural changes might increase the risk of thrombosis in liver transplant recipients.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002504/pdfft?md5=35fdaba75960d81f8bd6a4437c8506af&pid=1-s2.0-S2475037924002504-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167780","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":"Prescription and switching patterns of direct oral anticoagulants in patients with atrial fibrillation","authors":"","doi":"10.1016/j.rpth.2024.102544","DOIUrl":"10.1016/j.rpth.2024.102544","url":null,"abstract":"<div><h3>Background</h3><p>The patterns of direct oral anticoagulant (DOAC) selection and switching to a different oral anticoagulant (OAC) in patients with atrial fibrillation (AF) are unknown.</p></div><div><h3>Objectives</h3><p>To describe temporal patterns in first DOAC prescriptions, estimate the incidence, and identify predictors of switching to a different OAC within 1 year in OAC-naive AF patients.</p></div><div><h3>Methods</h3><p>In this retrospective cohort study, using a near-nationwide prescription registry (IQVIA, the Netherlands), we determined the number of patients per month initiated on each DOAC and identified predictors of switching within 1 year with robust Poisson regression.</p></div><div><h3>Results</h3><p>We included 94,874 patients. From November 2015 to November 2019, the monthly use of apixaban (<em>n</em> = 366 to <em>n</em> = 1066, +191%), rivaroxaban (<em>n</em> = 379 to <em>n</em> = 868, +129%), and edoxaban (<em>n</em> = 2 to <em>n</em> = 305, +15,150%) increased, whereas that of dabigatran decreased (<em>n</em> = 317 to <em>n</em> = 179, −44%). In the 66,090 patients with ≥1 year of available calendar time, 7% switched to a different OAC within 1 year. Strong predictors of switching to a different DOAC were using dabigatran (adjusted risk ratio [aRR], 3.33; 95% CI, 3.02-3.66) or edoxaban (aRR, 1.56; 95% CI, 1.34-1.82) rather than apixaban and using a standard DOAC dose (aRR, 2.54; 95% CI, 2.23-2.88). Strong predictors of switching to a vitamin K antagonist were using rivaroxaban (aRR, 1.36; 95% CI, 1.19-1.54 vs apixaban) and using a standard DOAC dose (aRR, 1.49; 95% CI, 1.26-1.77).</p></div><div><h3>Conclusion</h3><p>In the Netherlands, factor Xa inhibitors are increasingly being selected for OAC-naive AF patients. Seven percent of patients switch to a different OAC within 1 year, and the initial DOAC type and dose are strong predictors of switching.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002395/pdfft?md5=3e676a8fe1eef5cad271dceb451f5210&pid=1-s2.0-S2475037924002395-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142129542","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":"Cross-reacting antiporcine factor VIII inhibitors in patients with acquired hemophilia A","authors":"","doi":"10.1016/j.rpth.2024.102553","DOIUrl":"10.1016/j.rpth.2024.102553","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002486/pdfft?md5=5cde6793d058b57ee44e1f45bb26b89d&pid=1-s2.0-S2475037924002486-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142167786","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 risk of venous thromboembolism in primary central nervous system lymphoma: a systematic review and meta-analysis","authors":"","doi":"10.1016/j.rpth.2024.102507","DOIUrl":"10.1016/j.rpth.2024.102507","url":null,"abstract":"<div><p>Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma localized to the central nervous system. Small single-center studies have suggested that patients with PCNSL may be at high risk of venous thromboembolism (VTE). This systematic review aimed to estimate the risk of VTE in patients with PCNSL. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MEDLINE, Embase, and CINAHL were searched from 1990 to 2022. Prospective and retrospective observational studies as well as clinical trials were included. The primary efficacy outcome was VTE, and the primary safety outcome was major bleeding as defined by the individual studies. After screening 883 studies, 46 studies (3688 patients) with PCNSL were included. Mean age was 62.4 years. Five studies explored the use of thromboprophylaxis (acetyl salicylic acid or anticoagulation [<em>n</em> = 1]) and low-molecular-weight heparin (<em>n</em> = 4). Overall, 420 patients developed VTE (11.4%), including 17 fatal events (4% of all VTE). Two studies that reported on VTE prophylaxis representing 77 patients identified 8 breakthrough VTE events (10.4%). Most studies (<em>n</em> = 34; 74.5%) did not report major bleeding complications. Among studies reporting on bleeding, 174 major bleeding (7.4%) events were reported out of 2361 patients, 3 of which were attributed to thromboprophylaxis. Patients with PCNSL seem to be at high risk of both VTE and bleeding complications. Future clinical trials in this population should routinely collect data on incidence of VTE and bleeding to help clinicians assess the risk-to-benefit ratio of thromboprophylaxis in this high-risk patient population.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002024/pdfft?md5=f1aacc9589f46720801fcbde42f4fb3a&pid=1-s2.0-S2475037924002024-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141706791","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":"LAIR-1 and PECAM-1 function via the same signaling pathway to inhibit GPVI-mediated platelet activation","authors":"","doi":"10.1016/j.rpth.2024.102557","DOIUrl":"10.1016/j.rpth.2024.102557","url":null,"abstract":"<div><h3>Background</h3><p>Inhibition of platelet responsiveness is important for controlling thrombosis. It is well established that platelet endothelial cell adhesion molecule-1 (PECAM-1) serves as a physiological negative regulator of platelet-collagen interactions. We recently demonstrated that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a negative regulator of platelet production and reactivity. It is however not known if LAIR-1 and PECAM-1 function in the same or different inhibitory pathways.</p></div><div><h3>Objectives</h3><p>In this study, we investigated the role of LAIR-1 alongside PECAM-1 in megakaryocyte development and platelet production and determined the functional redundancy through characterization of a LAIR-1/PECAM-1 double knockout (DKO) mouse model.</p></div><div><h3>Methods</h3><p>LAIR-1 and PECAM-1 expression in megakaryocytes were evaluated by western blotting. Megakaryocyte ploidy and proplatelet formation were evaluated by flow cytometry and fluorescent microscopy. Platelet function and signalling were compared in wild-type, <em>LAIR-1^{^−/−}</em>, <em>PECAM-1^{^−/−}</em> and DKO mice using aggregometry, flow cytometry and western blotting. Thrombosis was evaluated using the FeCl_₃ carotid artery model.</p></div><div><h3>Results</h3><p>We show that LAIR-1/PECAM-1 DKO mice exhibit a 17% increase in platelet count. Bone marrow-derived megakaryocytes from all 3 mouse models had normal ploidy <em>in vitro</em>, suggesting that neither LAIR-1 nor PECAM-1 regulates megakaryocyte development. Furthermore, relative to wild-type platelets, platelets derived from LAIR-1, PECAM-1, and DKO mice were equally hyperresponsive to collagen <em>in vitro</em>, indicating that LAIR-1 and PECAM-1 participate in the same inhibitory pathway. Interestingly, DKO mice exhibited normal thrombus formation <em>in vivo</em> due to DKO mouse platelets lacking the enhanced Src family kinase activation previously shown in platelets from LAIR-1-deficient mice.</p></div><div><h3>Conclusion</h3><p>Findings from this study reveal that LAIR-1 and PECAM-1 act to inhibit GPVI-mediated platelet activation via the same signaling pathway. Mice lacking LAIR-1 and PECAM-1 do not however exhibit an increase in thrombus formation despite minor increase in platelet count and reactivity to collagen. This study adds to the growing evidence that immunoreceptor tyrosine-based inhibition motif–containing receptors are important regulators of platelet count and function.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002528/pdfft?md5=28e276c6f50262cd61f9ab527bcbe16e&pid=1-s2.0-S2475037924002528-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242615","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":"Pharmacokinetics and pharmacodynamics of low doses of recombinant tissue plasminogen activator to establish a model for biosimilarity comparisons","authors":"","doi":"10.1016/j.rpth.2024.102518","DOIUrl":"10.1016/j.rpth.2024.102518","url":null,"abstract":"<div><h3>Background</h3><p>Recombinant tissue plasminogen activator (rt-PA) is a thrombolytic agent and essential in emergency medical care. Given recent supply shortages, the availability of biosimilar products is an urgent medical need. However, biosimilarity trials are difficult to perform in critically ill patients.</p></div><div><h3>Objectives</h3><p>The aim of this pilot study was to investigate the pharmacokinetics and pharmacodynamics of low rt-PA doses to establish a model for testing proposed biosimilars in healthy volunteers.</p></div><div><h3>Methods</h3><p>Eight healthy volunteers received 0.02 to 0.05 mg/kg rt-PA on 3 study days; blood samples were obtained every 4 minutes after the end of the bolus infusion to measure rt-PA antigen levels by enzyme immunoassay, and the pharmacodynamics were assessed with rotational thromboelastometry.</p></div><div><h3>Results</h3><p>Bolus infusion of low rt-PA doses was safe and well tolerated. Maximal plasma concentrations and the area under the curve increased dose-dependently. Time-concentration curves were clearly separated between the lower and the higher doses. As expected, the half-live of rt-PA was short (4.5-5 min), and representative for therapeutic doses. The intrasubject coefficient variations were moderate (&lt;25%). Bolus infusion of rt-PA dose-dependently shortened lysis time and lysis onset time in both dose groups and caused maximum clot lysis of 100% in all participants.</p></div><div><h3>Conclusion</h3><p>In conclusion, the pharmacokinetics of rt-PA was dose linear and displayed limited intrasubject variability even at subtherapeutic doses. The half-life and thus clearance of rt-PA was representative of full therapeutic doses. The lysis time was shortened in a dose and time-dependent fashion and was clearly distinguishable between doses. Thus, the model appears to be suitable and sensitive to test biosimilarity.</p></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2475037924002139/pdfft?md5=dfff651ba8e76ba6cb98ae530b39fe12&pid=1-s2.0-S2475037924002139-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142048046","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}