Thrombosis and haemostasis最新文献

{"title":"Percutaneous Coronary Intervention in Acute Coronary Syndrome with Mild-to-Moderate Thrombocytopenia.","authors":"Yicong Ye, Yongchen Hao, Xiliang Zhao, Jun Liu, Na Yang, Sidney C Smith, Yong Huo, Gregg C Fonarow, Junbo Ge, Louise Morgan, Zhaoqing Sun, Danqing Hu, Yiqian Yang, Chang-Sheng Ma, Dong Zhao, Yaling Han, Jing Liu, Yong Zeng","doi":"10.1055/a-2225-5263","DOIUrl":"10.1055/a-2225-5263","url":null,"abstract":"<p><strong>Background: </strong> Baseline thrombocytopenia is commonly observed in patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI).</p><p><strong>Aim: </strong> The purpose of this analysis was to investigate safety and effectiveness of PCI in ACS patients with baseline mild-to-moderate thrombocytopenia.</p><p><strong>Methods: </strong> The data were collected from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. A total of 50,009 ACS patients were recruited between July 2017 and December 2019. Among them, there were 6,413 patients with mild-to-moderate thrombocytopenia, defined as a platelet count of ≥50 × 10⁹/L and <150 × 10⁹/L on admission. The primary outcome was in-hospital net adverse clinical events (NACE), consisting of major adverse cardiac events (MACE) and major bleeding events. The associations between PCI and in-hospital outcomes were analyzed by inverse probability treatment weighting (IPTW) method.</p><p><strong>Results: </strong> PCI was performed in 4,023 of 6,413 patients (62.7%). The IPTW analysis showed that PCI was significantly associated with a reduced risk of in-hospital MACE (odd ratio [OR]: 0.45; 95% confidence interval [CI]: 0.31-0.67; <i>p</i> < 0.01) and NACE (OR: 0.59; 95% CI: 0.42-0.83; <i>p</i> < 0.01). PCI was also associated with an increased risk of any bleeding (OR: 1.56; 95% CI: 1.09-2.22; <i>p</i> = 0.01) and minor bleeding (OR: 1.52; 95% CI: 1.00-2.30; <i>p</i> = 0.05), but not major bleeding (OR: 1.51; 95% CI: 0.76-2.98; <i>p</i> = 0.24).</p><p><strong>Conclusion: </strong> Compared with medical therapy alone, PCI is associated with better in-hospital outcomes in ACS patients with mild-to-moderate thrombocytopenia. Further studies with long-term prognosis are needed.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"218-229"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Inhibitory Single-Domain Antibody against Protein Z-Dependent Protease Inhibitor Promotes Thrombin Generation in Severe Hemophilia A and FXI Deficiency.","authors":"Claire Auditeau, Tung-Son Nguyen, Floriane Devaux, François Saller, Ivan Peyron, Adeline Blandinières, Christelle Repérant, Sadyo Daramé, Cécile V Denis, Peter Lenting, Delphine Borgel, Elsa P Bianchini","doi":"10.1055/a-2373-2829","DOIUrl":"10.1055/a-2373-2829","url":null,"abstract":"<p><strong>Background: </strong> Protein Z-dependent protease inhibitor (ZPI) is an anticoagulant serpin that targets factor Xa (FXa) in the presence of protein Z (PZ), and factor XIa (FXIa). In factor-VIII-deficient mice, PZ or ZPI gene knock-out mitigates the bleeding phenotype, and pharmacological inhibition of PZ enhances thrombin generation in plasma from patients with hemophilia.</p><p><strong>Aims: </strong> To develop a single-domain antibody (sdAb) directed against ZPI to inhibit its anticoagulant activity.</p><p><strong>Methods: </strong> We screened for anti-ZPI sdAbs in a llama-derived phage display immune library of sdAbs. The sdAbs that bound ZPI were produced and purified for characterization. The binding of sdAbs to ZPI or other serpins was evaluated using ELISAs, and ZPI inhibition was measured in an anti-FXa or anti-FXIa chromogenic assay. The sdAbs's procoagulant activity was assessed in a thrombin generation assay in normal plasma, factor VIII- and FXI-deficient plasma.</p><p><strong>Results: </strong> Of the four sdAbs found to bind to ZPI, one (referred to as ZPI-sdAb2) dose-dependently inhibited ZPI's anti-FXa and anti-FXIa activities with a mean half-maximal inhibitory concentration of 1.8 and 1.3 µM, respectively. ZPI-sdAb2 did not cross-react with other plasma serpins, such as antithrombin and α1-antitrypsin. ZPI-sdAb2 induced a significant increase in thrombin generation in plasma samples from healthy donors, patients with severe hemophilia A, and patients with FXI deficiency.</p><p><strong>Conclusion: </strong> ZPI-sdAb2 is the first specific, direct ZPI inhibitor found to exhibit procoagulant activity in plasma. This sdAb might have potential as a treatment for hemophilia or other bleeding disorders.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"207-217"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbamylation-A Pathologic Posttranslational Modification Affecting Platelet and Von Willebrand Factor Function during Uremic Kidney Disease.","authors":"Rory R Koenen","doi":"10.1055/s-0044-1791550","DOIUrl":"10.1055/s-0044-1791550","url":null,"abstract":"","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"241-242"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354311","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}

{"title":"Risk of Depression after Venous Thromboembolism in Patients with Hematological Cancer: A Population-Based Cohort Study.","authors":"Daniel Steiner, Erzsébet Horváth-Puhó, Helle Jørgensen, Kristina Laugesen, Cihan Ay, Henrik Toft Sørensen","doi":"10.1055/a-2225-5428","DOIUrl":"10.1055/a-2225-5428","url":null,"abstract":"<p><strong>Background: </strong> Venous thromboembolism (VTE) may complicate the clinical course of cancer patients and add to their psychological burden.</p><p><strong>Objectives: </strong> We aimed to investigate the association between VTE and risk of subsequent depression in patients with hematological cancer.</p><p><strong>Patients and methods: </strong> We conducted a population-based cohort study using Danish national health registries. Between 1995 and 2020, we identified 1,190 patients with hematological cancer and incident VTE diagnosed within 6 months before to 1 year after cancer diagnosis. A comparison cohort of patients with hematological cancer without VTE (<i>n</i> = 5,325) was matched by sex, year of birth, cancer type, and year of cancer diagnosis. Patients were followed until diagnosis of depression, emigration, death, study end (2021), or for a maximum of 3 years. Depression was defined as hospital discharge diagnosis of depression or ≥1 prescription for antidepressants. Absolute risks of depression were computed with cumulative incidence functions, treating death as competing event. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using Cox proportional hazards regression models, adjusting for comorbidities.</p><p><strong>Results: </strong> Depression was observed in 158 hematological cancer patients with and 585 without VTE. The 3-year absolute risks of depression were 13.3% (95% CI: 11.5-15.3%) in the VTE cancer cohort and 11.1% (95% CI: 10.3-12.0%) in the comparison cancer cohort, corresponding to a risk difference of 2.2% (95% CI: -1.8-6.5%). VTE was associated with an increased relative risk of depression (adjusted HR: 1.56, 95% CI: 1.28-1.90).</p><p><strong>Conclusion: </strong> VTE was associated with an elevated risk of subsequent depression in patients with hematological cancer.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"255-264"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138800703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems.","authors":"Grace C Herron, Deborah DeCamillo, Xiaowen Kong, Brian Haymart, Scott Kaatz, Stacy Ellsworth, Mona A Ali, Christopher Giuliano, James B Froehlich, Geoffrey D Barnes","doi":"10.1055/a-2365-8681","DOIUrl":"10.1055/a-2365-8681","url":null,"abstract":"<p><strong>Background: </strong> While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment.</p><p><strong>Objectives: </strong> We aimed to better characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention.</p><p><strong>Methods: </strong> We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI²) registry, a retrospective quality-improvement process using data abstractors, from 2018 to 2022 on the number of \"alerts\" that are generated in response to dosing deviating from the U.S. Food and Drug Administration instructions for atrial fibrillation (AF) and venous thromboembolism (VTE).</p><p><strong>Results: </strong> Among a sample of 789 to 1,022 annual AF patients and 381 to 484 annual VTE patients prescribed a DOAC in the MAQI² registry, off-label dosing was relatively common. Over the 5-year period (2018-2022), there were 569 alerts for AF patients and 162 alerts for VTE patients. Alerts occurred more frequently during follow-up than at the time of initial prescribing in AF patients (78.2 vs. 21.8%), but more commonly at initial prescribing in VTE patients (59.9 vs. 40.1%). After initial review by quality-improvement abstractors, 19.3% of AF alerts and 14.8% of VTE alerts resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention about 75% of the time for both populations. The most common intervention was a change in DOAC dosing.</p><p><strong>Conclusion: </strong> This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC, particularly for patients with AF, as off-label prescribing occurs frequently during the follow-up period.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"278-285"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbamylation is Instrumental in End-Stage Kidney Disease Coagulopathies: The Impact on von Willebrand Factor and Platelet Functionality.","authors":"Janka Babickova, Urszula Kałucka, Alicja Sochaj-Grzegorczyk, Jan Potempa, Carsten Scavenius, Thomas Knoop, Hans-Peter Marti, Marta Kaminska, Piotr Mydel","doi":"10.1055/a-2373-3792","DOIUrl":"10.1055/a-2373-3792","url":null,"abstract":"<p><strong>Background: </strong> Chronic kidney disease (CKD) is a progressive, irreversible, and incurable condition characterized by high morbidity and mortality, affecting approximately one-tenth of the global population. Rise of urea-derived cyanate levels in CKD patients, severalfold higher in comparison to those found in healthy individuals, leads to an increased rate of carbamylation of lysine residues of proteins and peptides. This posttranslational modification plays an important role in the progression of kidney failure but also in the onset of CKD-related complications, including previously reported coagulopathies. In this study, we have explored the impact of carbamylation on the functionality of von Willebrand factor (vWF), a pivotal player in hemostasis, and its implications for platelet adhesion.</p><p><strong>Materials and methods: </strong> We have explored carbamylated vWF's interactions with its partner proteins via ELISA. Mass spectrometry was employed to identify modified lysine residues. Blood platelets isolated from healthy donors were carbamylated, and their activation, binding to endothelium and thromboxane release were evaluated using flow cytometry, adhesion assays and ELISA, respectively.</p><p><strong>Results: </strong> Using mass spectrometry we detected the vWF's lysine residue smost susceptible to carbamylation. This modification has in turn affected vWF's interactions with its key binding partners: decreased binding to collagen types I/III but increased the affinity to factor FVIII, while its binding to fibrinogen remained unchanged. Carbamylation of vWF impeded vWF-blood platelet binding, but carbamylation of platelets led to their increased thrombin-dependent activation as observed by enhanced phosphatidylserine exposure, improved their binding to vascular endothelium, at the same time decreasing the production of the prothrombotic mediator, thromboxane A2.</p><p><strong>Conclusion: </strong> Our findings highlight the multifaceted impact of carbamylation on vWF and platelets, disturbing the delicate balance of coagulation cascade. These alterations could contribute to the complex hemostatic imbalance in ESKD, underscoring the need for further research to fully understand these mechanisms and their clinical implications.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":"230-240"},"PeriodicalIF":5.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11858613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141760999","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}

{"title":"Utility of Sepsis-induced Coagulopathy among Disseminated Intravascular Coagulation Diagnostic Criteria: A Multicenter Retrospective Validation Study.","authors":"Satoshi Gando, Takeshi Wada, Kazuma Yamakawa, Toshikazu Abe, Seitaro Fujishima, Shigeki Kushimoto, Toshihiko Mayumi, Hiroshi Ogura, Daizoh Saitoh, Atsushi Shiraishi, Yutaka Umemura, Yasuhiro Otomo","doi":"10.1055/a-2530-7553","DOIUrl":"10.1055/a-2530-7553","url":null,"abstract":"<p><strong>Background: </strong> The criteria for diagnosing sepsis-induced coagulopathy (SIC) may overlap with those of Japanese Association for Acute Medicine (JAAM) disseminated intravascular coagulation (DIC). This study determined if the diagnostic criteria of SIC overlap with JAAM DIC diagnostic criteria for identifying patients with DIC according to the International Society on Thrombosis and Haemostasis (ISTH) criteria and whether the patients diagnosed with these criteria have the same prognosis.</p><p><strong>Methods: </strong> This multicenter retrospective study included patients with sepsis diagnosed using the JAAM and ISTH DIC and SIC criteria on days 1 and 4. The established ISTH DIC criteria was the reference standard for primary outcome that compared the characteristics of SIC and JAAM DIC. Secondary outcomes were multiple organ dysfunction syndrome (MODS), ventilator-free and intensive care unit-free days, and in-hospital mortality.</p><p><strong>Results: </strong> A total of 1,438 patients were included in this study. On day 1, the JAAM DIC and SIC criteria diagnosed almost all patients with ISTH DIC (98 and 94%, respectively), predicting ISTH DIC (area under the receiver operating curve [AUC]: 0.740 versus 0.752, <i>p</i> = 0.523) and MODS (AUC: 0.686 versus 0.697, <i>p</i> = 0.546) on day 4 and progressing to ISTH DIC in the same proportion (28.6 versus 30.1%, <i>p</i> = 0.622). There were no differences in survival probabilities (<i>p</i> = 0.196) or secondary outcomes between patients diagnosed using JAAM DIC and SIC criteria on day 1.</p><p><strong>Conclusion: </strong> SIC and JAAM DIC diagnoses were equal among patients with sepsis, suggesting that SIC criteria add little to current DIC scoring systems.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Correction of Wiskott-Aldrich syndrome iPS Cells Rescues Proplatelet Defects and Improves Platelet Size.","authors":"Praewphan Ingrungruanglert, Sarinya Phodang, Pramuk Amarinthnukrowh, Phattarawan Meehart, Pornpitra Pratedrat, Narissara Suratannon, Vorasuk Shotelersuk, Kanya Suphapeetiporn, Nipan Israsena","doi":"10.1055/a-2508-0983","DOIUrl":"10.1055/a-2508-0983","url":null,"abstract":"<p><p>Wiskott-Aldrich syndrome (WAS) is a severe X-linked disorder caused by loss-of-function mutations in the <i>WAS</i> gene, responsible for encoding WAS protein (WASP), a key regulator of the actin cytoskeleton in all hematopoietic cells, except red blood cells. The mechanism underlying microthrombocytopenia, a distinctive feature of WAS and a major contributor to mortality, remains not fully elucidated. In this study, using different gene-editing strategies, we corrected mutations in patient-derived WAS-induced pluripotent stem cell (iPSC) lines, generating isogeneic WAS-iPSC lines. These included lines with direct mutation-specific correction and lines incorporating a <i>WASP</i> transgene cassette regulated by the MND or WAS1.6 kb promoter integrated at the safe harbor AAV1 site. Our results demonstrated that direct mutation correction successfully restored WASP levels to the equivalent of the wild-type in iPSC-derived megakaryocytes (MKs). In contrast, the AAV1-targeted strategy using the MND and WAS1.6 promoters yielded a lower level of WASP. Notably, only the mutation-specific correction lines exhibited improvements in proplatelet structures and generated larger-sized platelets. Our findings underscore the crucial roles of WASP during human thrombopoiesis and suggest that therapeutic approaches, such as direct gene correction, which can achieve physiologic levels of WASP in MKs, hold promise for ameliorating platelet defects in individuals with WAS.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Pulmonary Embolism Risk Stratification: The National Early Warning Score and Its Integration into the ESC Classification.","authors":"Karin Janata, Alexandra Julia Lipa, Anne Merrelaar, Marieke Merrelaar, Ursula Azizi-Semrad, Harald Herkner, Michael Schwameis, Juergen Grafeneder","doi":"10.1055/a-2544-3626","DOIUrl":"https://doi.org/10.1055/a-2544-3626","url":null,"abstract":"<p><strong>Background: </strong>Pulmonary embolism (PE) requires accurate risk assessment. We investigated the prognostic performance of the National Early Warning Score (NEWS) in emergency department patients with PE.</p><p><strong>Methods: </strong>We included patients ≥ 18 years from our PE registry (2017 to 2021), excluding patients after cardiac arrest or intubation before admission. The primary outcome was a composite of 30-day all-cause mortality or the need for advanced therapy (i.e., systemic or catheter-directed thrombolysis). We used logistic regression and Cox proportional hazards models to estimate associations. PESI and ESC classification served as covariates. The overall score performances were quantified using receiver operating characteristic analysis.</p><p><strong>Results: </strong>We included 524 patients. Each increase in NEWS points increased the odds of the primary outcome by 69% (odds ratio 1.69, 95% CI: 1.51 -1.89, p < 0.001) and 30-day mortality by 44% (hazard ratio 1.44, 95% CI 1.30- 1.60, p < 0.001). Within the ESC intermediate-high and high-risk group, the 30-day mortality rate was higher in patients with a NEWS ≥ 7 compared to NEWS < 7 (24% vs 1%, p < 0.001). With a NEWS ≥ 7, 30-day mortality was lower in patients who received advanced therapy (18% vs. 39%), but not significantly. The NEWS predicted the primary outcome better than the Pulmonary Embolism Severity Index (AUC 0.853 vs. 0.752, p < 0.001).</p><p><strong>Conclusions: </strong>The NEWS was associated with 30-day mortality and the need for advanced therapy. Incorporating the NEWS into the ESC classification could help to assess patient outcomes early and thus support timely treatment decisions.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte/Macrophage Infiltration in Thrombus and Outcomes of Stroke Patients with Monocyte/Macrophage-dominant Thrombus.","authors":"Kijeong Lee, Myoung-Jin Cha, Il Kwon, Sungeun Kim, Jin Ju Song, Young Dae Kim, Hyo Suk Nam, Jaseong Koo, Hye Sun Lee, Haram Joo, Hyunjung Choi, Ji Hoe Heo","doi":"10.1055/a-2513-9638","DOIUrl":"https://doi.org/10.1055/a-2513-9638","url":null,"abstract":"<p><strong>Background: </strong> Inflammatory cells may play a role in thrombus formation. However, the impact of monocytes in thrombosis and clinical characteristics of patients with monocyte-rich thrombus are less well understood.</p><p><strong>Methods: </strong> A FeCl₃-induced carotid thrombosis model in mice was used to study aged thrombus by ligating the distal carotid artery for 0.5, 1, 2, 3, 6, 24, 48, or 72 hours. In stroke patients, we used thrombi that were obtained during endovascular thrombectomy. Immunohistochemistry was performed to determine thrombus composition. We investigated monocyte/macrophage recruitment to arterial thrombus over time in mice, and compared clinical outcomes between stroke patients with the higher and the lower monocyte/macrophage compositions in thrombus.</p><p><strong>Results: </strong> In 90 mice, CD68 (monocyte/macrophage) counts increased from 3 hours in a time-dependent manner, and decreased after 48 hours (<i>p</i> < 0.001). In 102 stroke patients, the higher monocyte/macrophage group had higher blood platelet counts (median 228 × 10⁹/L, interquartile range [177-267] versus median 186 × 10⁹/L, interquartile range [164-225], <i>p</i> = 0.036), less frequently parenchymal hematoma (8.0% versus 28.8%, <i>p</i> = 0.007), and more frequently functional independence (54.0% versus 32.7%, <i>p</i> = 0.030). In multivariable logistic regression analysis, the higher monocyte/macrophage group was independently associated with functional independence (odds ratio 4.954, 95% confidence interval 1.467-16.724, <i>p</i> = 0.010).</p><p><strong>Conclusion: </strong> Monocytes/macrophages increasingly infiltrated the thrombus after a few hours in mouse arterial thrombosis model, suggesting their role in later stages rather than initial stages of thrombosis. Stroke patients with higher monocyte/macrophage counts had less frequent parenchymal hematoma and more frequent functional independence, suggesting that monocyte/macrophage-rich thrombi are a predictor of better clinical outcomes.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441925","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}