Thrombosis research最新文献

{"title":"Direct oral anticoagulant prescribing trends for venous thromboembolism among adult patients with obesity at University of Utah Health","authors":"Hailey L. Vandenhazel ,&nbsp;Aaron S. Wilson ,&nbsp;Xiangyang Ye ,&nbsp;Sara R. Vazquez ,&nbsp;Daniel M. Witt","doi":"10.1016/j.thromres.2024.109216","DOIUrl":"10.1016/j.thromres.2024.109216","url":null,"abstract":"<div><h3>Background</h3><div>Anticoagulants, including warfarin and direct oral anticoagulants (DOACs), are used to prevent and treat venous thromboembolism (VTE) which is common in patients with obesity. Guidance statements regarding use of DOACs for VTE treatment in this patient population have been updated.</div></div><div><h3>Objective</h3><div>Examine DOAC prescribing trends in patients with obesity and VTE.</div></div><div><h3>Methods</h3><div>We performed a retrospective, single-site cross-sequential study of DOAC prescribing trends in adult patients with obesity (BMI <em>≥</em>30) and objectively confirmed VTE diagnosis between 2014 and 2022. The primary outcome of interest was the proportion of patients with obesity prescribed DOACs.</div></div><div><h3>Results</h3><div>A total of 1826 patients were included in our analysis. Most patients were of White race (85.8 %) and approximately half were female. Pulmonary embolism was the most common VTE type (62.2 %). A total of 1018 patients were prescribed DOAC therapy (55.8 %), 524 warfarin therapy (28.7 %), and 284 enoxaparin (15.6 %). Logistic regression analysis revealed that the utilization of DOACs exhibited a significant upward trend from 2017 to 2022 (odds ratio [OR] 1.85 to 14.08 compared to 2014), but not from 2015 to 2016 (OR 1.30 to 1.52). Patients with BMI ≥ 40 and ≥ 50 were twice and 4-times as likely to be prescribed warfarin than DOACs, respectively.</div></div><div><h3>Conclusion</h3><div>Between 2017 and 2022, the proportion of patients with obesity prescribed DOACs for the treatment of VTE increased significantly. This suggests an increasing likelihood to prescribe DOACs in this patient population despite the lack of safety and efficacy data from randomized controlled trials except for very heavy patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109216"},"PeriodicalIF":3.7,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial and circulating progenitor cells as prognostic biomarkers of stroke: A systematic review and meta-analysis","authors":"Juan Francisco García Granado ,&nbsp;Francisco Javier Rodríguez Esparragón ,&nbsp;Jesús María González Martín ,&nbsp;Sara E. Cazorla Rivero ,&nbsp;Ayoze Nauzet González Hernández","doi":"10.1016/j.thromres.2024.109224","DOIUrl":"10.1016/j.thromres.2024.109224","url":null,"abstract":"<div><h3>Purpose</h3><div>Endothelial progenitor cells (EPCs) are biomarkers of neurovascular repair in cerebral vascular disease (CVD). Low quantification of EPCs and/or their dysfunction has been associated with stroke severity and post-stroke functionality. This systematic review (SR) and meta-analysis aimed to analyze whether EPC quantification contributes to stroke severity and functional prognosis.</div></div><div><h3>Methods</h3><div>Articles were selected from the PubMed, ScienceDirect, and Ovid MEDLINE databases, according to the guidelines of the PRISMA 2020 [<span><span>1</span></span>] statement. Detailed observational studies of samples from subjects with a clinical diagnosis of CVD (ischemic stroke-IS, hemorrhagic stroke-HS, or transient ischemic attack-TIA) aged &gt;45 years during 2003–2023 were included. Evaluation of study quality was based on the Critical Appraisal Skills Programme checklist(Santamaría, 2017 [<span><span>2</span></span>]).</div></div><div><h3>Results</h3><div>We included 22 articles in our SR. Patients with IS and good functional outcomes had higher EPC levels during the first week of admission than those with worse functional outcomes. Higher EPC levels were associated with reduced infarct growth, improved NIHSS scores at 48 h (OR 0.8; 95 % CI: 0.72–0.90; <em>p</em> &lt; 0.0002) 7 (<em>r</em> = −0.607; <em>p</em> &lt; 0.0001), and 90 days (<em>r</em> = −0.570; p &lt; 0.0001), with a negative correlation between EPC levels and NIHSS score (overall pooled r = −0,32, 95 % CI: −0.39-0.24), and good functional outcomes with better mRS scores at 24 h, 3, 6, and 12 months (overall pooled SMD 4.51, CI 95 %: 0.70–0.83). Lower EPC quantification and worse functional outcomes during admission were predictors of IS recurrence. Higher EPC levels were associated with better functional outcomes and lower bleeding volumes in patients with HS and were protective markers for the progression high-risk TIA.</div></div><div><h3>Conclusion</h3><div>EPCs seems to be predictive biomarkers of better clinical outcomes in patients with CVD, exhibiting lower severity (NIHSS) and better functional prognosis (mRS).</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109224"},"PeriodicalIF":3.7,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematology products from snake venoms","authors":"David Green MD, PhD","doi":"10.1016/j.thromres.2024.109215","DOIUrl":"10.1016/j.thromres.2024.109215","url":null,"abstract":"<div><div>Venoms have primarily been used to prepare antivenoms for the treatment of snake bites, but they have constituents that might serve other medical needs. These include metalloproteinases, serine proteases, phospholipases, and C-type lectin-like proteins. Some of the products that have been prepared from venoms are procoagulants employed as topical hemostatics, and either applied directly to bleeding wounds or used as adjuncts to surgical procedures to assist in controlling blood loss. Venoms are also a valuable source of laboratory reagents helpful in diagnosing specific coagulation factor deficiencies, identifying lupus anticoagulants, or managing therapeutic anticoagulation. In addition, the unique properties of certain venom components have led to their use as antithrombotic agents. This review describes how snake venoms have provided insight into coagulation mechanisms and generated products to improve human health. Venomous snakes are dangerous but we must learn to safely share our planet with them, not least because studies of their venoms might lead to the discovery of valuable biomolecules.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109215"},"PeriodicalIF":3.7,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing therapeutic enoxaparin in preterm neonates and infants","authors":"Madeline Abbott (Grossman) ,&nbsp;Anna Bustin O'Brien ,&nbsp;Kelsie Ellis ,&nbsp;Hilary Whitworth ,&nbsp;Christopher Thom","doi":"10.1016/j.thromres.2024.109214","DOIUrl":"10.1016/j.thromres.2024.109214","url":null,"abstract":"<div><h3>Objectives</h3><div>The purpose of this study was to describe the enoxaparin dose required by preterm neonates and infants to achieve therapeutic anti-Xa levels.</div></div><div><h3>Study design</h3><div>Retrospective chart review of preterm infants, &lt;12 weeks postnatal age, born before 37 weeks gestation, receiving subcutaneous (SUBQ) enoxaparin every 12 h (q12h) with an anti-Xa goal of 0.5–1 units/mL. The primary endpoint was the enoxaparin dose required to achieve a therapeutic anti-Xa level. Secondary endpoints included initial enoxaparin dose and the frequency of achieving therapeutic anti-Xa levels with the initial dose, index thrombus progression, formation of new thrombi, and suspected or confirmed bleeding.</div></div><div><h3>Results</h3><div>Fifty-six patients were included for analysis. At time of enoxaparin initiation, the median gestational age, post-menstrual age, and weight were 34 weeks and 2 days, 38 weeks and 4 days, and 2.5 kg (kg), respectively. The median dose required to achieve a therapeutic anti-Xa was 2 mg/kg (IQR 1.7–2.6 mg/kg) SUBQ q12h. The median initial enoxaparin dose of 1.7 mg/kg SUBQ q12h aligned with formulary recommendations. Twenty-three patients (41 %) achieved a therapeutic anti-Xa with the initial dose. Follow-up ultrasounds were available for 38 patients, of which 3 (8 %) showed progression of the index thrombus and 5 (13 %) showed formation of a new thrombus. One patient discontinued enoxaparin due to pulmonary hemorrhage, necessitating protamine administration.</div></div><div><h3>Conclusions</h3><div>Preterm neonates appear to require a median enoxaparin dose of 2 mg/kg subcutaneously every 12 h to achieve therapeutic anti-Xa levels.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109214"},"PeriodicalIF":3.7,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protein disulfide isomerase 1 (PDIA1) regulates platelet-derived extracellular vesicle release","authors":"Agnieszka Pelesz ,&nbsp;Katarzyna Rafa-Zablocka ,&nbsp;Patrycja Kaczara ,&nbsp;Stefan Chlopicki ,&nbsp;Kamil Przyborowski","doi":"10.1016/j.thromres.2024.109209","DOIUrl":"10.1016/j.thromres.2024.109209","url":null,"abstract":"<div><h3>Background</h3><div>Protein disulfide isomerase 1 (PDIA1) and 3 (PDIA3) regulate platelet activation and thrombus formation. However, their role in the formation of platelet-derived extracellular vesicles (pEVs) remains unknown.</div></div><div><h3>Aim</h3><div>To characterise the effects of PDIA1 and PDIA3 inhibition on pEV formation in washed murine platelets in response to platelet glycoprotein VI (GPVI) receptor or intracellular calcium signal activation.</div></div><div><h3>Methods</h3><div>Washed platelets were isolated from C57BL/6 mice and activated using convulxin or the calcium ionophore A23187. Then, the resulting pEVs were analysed using nano flow cytometry (FC), platelet aggregation was measured by FC and a 96-well plate-based assay, and intracellular free calcium concentration ([Ca²⁺]i) was measured by indicator fluorescence. Platelet PDIs were blocked by a classic selective PDIA1 inhibitor (bepristat 2a) and sulphonamides of aziridine-2-carboxylic acid derivatives, novel PDI inhibitors relatively selective for PDIA1 or PDIA3 (C-3389 and C-3399, respectively). Clinically relevant antiplatelet drugs were used for comparison.</div></div><div><h3>Results</h3><div>Convulxin and A23187 concentration-dependently induced pEV formation. However, unlike convulxin, platelet activation by A23187 did not stimulate their aggregation. Bepristat 2a, C-3389 and C-3399 inhibited convulxin-induced pEV release accompanied by the reduction of [Ca²⁺]i. In contrast, only bepristat 2a inhibited A23187-induced pEV release, but without effect on [Ca²⁺]i. Cangrelor and tirofiban, but not acetylsalicylic acid (ASA), inhibited convulxin-induced pEV release, but neither of them inhibited A23187-induced pEV release.</div></div><div><h3>Conclusion</h3><div>The inhibition of PDIA1 represents a novel approach to inhibit pEV formation by a mechanism independent of platelet aggregation and calcium signaling.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109209"},"PeriodicalIF":3.7,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between coagulation activity and clinical and imaging outcomes in acute ischemic stroke patients - A sub-study of the MR CLEAN NO-IV trial","authors":"Angelique Ceulemans ,&nbsp;Aarazo Barakzie ,&nbsp;Henri M.H. Spronk ,&nbsp;Moniek P.M. de Maat ,&nbsp;Heleen M.M. van Beusekom ,&nbsp;Aladdin Taha ,&nbsp;Bart J. Emmer ,&nbsp;Yvo B.W.E.M. Roos ,&nbsp;Diederik W.J. Dippel ,&nbsp;Charles B.L.M. Majoie ,&nbsp;Wim H. van Zwam ,&nbsp;Hugo ten Cate ,&nbsp;Robert J. van Oostenbrugge ,&nbsp;Magdolna Nagy","doi":"10.1016/j.thromres.2024.109212","DOIUrl":"10.1016/j.thromres.2024.109212","url":null,"abstract":"<div><h3>Background</h3><div>The MR CLEAN NO-IV trial showed neither superiority nor noninferiority of endovascular treatment (EVT) alone compared to intravenous thrombolysis (IVT; Alteplase) before EVT in acute ischemic stroke (AIS) patients with large vessel occlusion of the anterior circulation. Although the treatment effect is largely attributable to EVT, IVT may affect hypercoagulability during AIS.</div></div><div><h3>Aims</h3><div>To investigate the association between activated coagulation and final infarct volume and clinical outcomes (modified Rankin Scale 3–6 and mortality 90 days post-EVT), and whether this effect is modified by IVT administration.</div></div><div><h3>Methods</h3><div>Enzyme-linked immunosorbent assays were used to quantify activated coagulation markers (activated coagulation factor (F) XIIa-C1 esterase inhibitor (C1inh); FXIIa-antithrombin (AT), FXIa-C1inh, FXIa-AT, FIXa-AT, FXa-AT, T-AT, FVIIa-AT) in plasma samples obtained on admission (T₀), 1 h post-EVT (T₁) and 24 h post-EVT (T₂). Multivariable regressions were performed to investigate the associations and effect modification.</div></div><div><h3>Results</h3><div>In the total cohort of 116 patients, a significant increase at T₁ was seen in FIXa-AT (<em>p</em> = .001), FXa-AT (<em>p</em> &lt; .001), T-AT (p &lt; .001), and FVIIa-AT (<em>p</em> = .012), while there was a significant increase at T₂ in FXIIa-C1inh (p &lt; .001). Similar results were seen in the IVT+EVT subgroup. The EVT alone subgroup showed a significant temporary increase at T₁ in FXa-AT (p &lt; .001) and T-AT (<em>p</em> = .014). Neither the enzyme:inhibitor complexes nor the interaction with IVT were significantly associated with the outcome measures.</div></div><div><h3>Conclusion</h3><div>Despite temporary significant increases in enzyme:inhibitor complexes in the IVT+EVT group, but not in the EVT alone group, there were no significant associations with final infarct volume and clinical outcomes.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"245 ","pages":"Article 109212"},"PeriodicalIF":3.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142688974","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":"A study of platelet function in patients with chronic immune thrombocytopenia treated with thrombopoietin receptor agonists","authors":"Christos Stafylidis ,&nbsp;Sevastianos Chatzidavid ,&nbsp;Panagiotis Diamantopoulos ,&nbsp;Dimitra Vlachopoulou ,&nbsp;Stavroula Syriopoulou ,&nbsp;Panagiota Katsiampoura ,&nbsp;Nefeli Giannakopoulou ,&nbsp;Abraham Pouliakis ,&nbsp;Ioanna Anastasopoulou ,&nbsp;Olga Katsarou ,&nbsp;Marina Mantzourani ,&nbsp;Nora-Athina Viniou","doi":"10.1016/j.thromres.2024.109211","DOIUrl":"10.1016/j.thromres.2024.109211","url":null,"abstract":"<div><h3>Background</h3><div>Thrombopoietin receptor agonists (TPO-RAs) are widely used in immune thrombocytopenia (ITP) and are associated with increased thrombotic risk. However, data regarding their impact on platelet function is scarce.</div></div><div><h3>Methods</h3><div>Platelet function was evaluated in chronic ITP patients enrolled over one year, using light transmission aggregometry and platelet-derived microparticle (PMP) levels measurement with flow cytometry. Aggregation responses to various concentrations of ADP, collagen, ristocetin, and PMP levels were compared between TPO-RA-treated patients, patients treated with other agents and healthy individuals.</div></div><div><h3>Results</h3><div>TPO-RA-treated patients (<em>n</em> = 24) displayed significantly reduced aggregation responses to 2.5 μM, 5 μM, and 10 μM of ADP and collagen compared to 15 healthy individuals (59.5 % vs. 87.6 %, <em>p</em> &lt; .0001, 43.6 % vs. 79.9 %, p &lt; .0001, 26.1 % vs. 75.2 %, p &lt; .0001, 67.2 % vs. 86 %, p &lt; .0001, respectively). Reduced responses to ADP and collagen were also recorded in patients treated with other agents (<em>n</em> = 16) compared to healthy controls but without difference between the two treatment groups. Aggregation response to ristocetin was normal in all three groups. None of the patients yielded enhanced platelet aggregation. In TPO-RA-treated patients, a strong positive correlation between platelet counts and aggregation response to ristocetin was observed (r_s = 0.65, <em>p</em> = .0005). PMP levels were significantly elevated in TPO-RA-treated patients compared to patients treated with other agents (49.5 vs 4.5 events/uL, <em>p</em> &lt; .0001) and healthy controls (5 events/uL, p &lt; .0001).</div></div><div><h3>Conclusions</h3><div>These results suggest that TPO-RAs may not enhance platelet aggregation responses, whereas impaired responses may be a disease feature. Furthermore, TPO-RAs may increase PMP levels and thus be implicated in the modulation of platelet function in ITP patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109211"},"PeriodicalIF":3.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionally distinct anticoagulant mechanisms of endothelial cells","authors":"Claudia Schönichen ,&nbsp;Siyu Sun ,&nbsp;Harmen Middelveld ,&nbsp;Dana Huskens ,&nbsp;Philip G. de Groot ,&nbsp;Johan W.M. Heemskerk ,&nbsp;Mark Roest ,&nbsp;Bas de Laat","doi":"10.1016/j.thromres.2024.109208","DOIUrl":"10.1016/j.thromres.2024.109208","url":null,"abstract":"<div><div>Antithrombin and tissue factor pathway inhibitor (TFPI) provide different anticoagulant mechanisms. Having established a potent anticoagulant role of cultured human umbilical vein endothelial cells in vessel-on-a-chip microfluidic models, we now investigated how these cells modulated thrombin generation under stasis through antithrombin and TFPI pathways. We observed that endothelial monolayers in 96 well-plates strongly delayed and suppressed the thrombin generation process induced by tissue factor, regardless of the presence of whole blood, platelet-rich plasma or platelet-free plasma. Intervention studies indicated that the blocking of heparin-like proteoglycans with polybrene or protamine sulphate, similarly as the absence of antithrombin in plasma, reverted the endothelial anticoagulant activity. Heparinase treatment of the cells also reduced the anticoagulant potential. Furthermore, the presence of andexanet-alpha (inactivated factor Xa) and an anti-TFPI antibody were able to revert the endothelial effects. Jointly, these data point to additive anticoagulant mechanisms of endothelial cells through surface-expressed heparin-like proteoglycans and TFPI, both contributing to thrombin inhibition.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109208"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of protein kinase C and the glycoprotein Ibα cytoplasmic tail in anti-glycoprotein Ibα antibody-induced platelet apoptosis and thrombocytopenia","authors":"Sai Zhang ,&nbsp;Chenglin Sun ,&nbsp;Qiuxia Huang,&nbsp;Jiahao Du,&nbsp;Yue Xia,&nbsp;Kangxi Zhou,&nbsp;Biao Yang,&nbsp;Kesheng Dai,&nbsp;Rong Yan","doi":"10.1016/j.thromres.2024.109210","DOIUrl":"10.1016/j.thromres.2024.109210","url":null,"abstract":"<div><h3>Introduction</h3><div>Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts. ITP patients with anti-platelet glycoprotein (GP) Ibα (a subunit of GPIb-IX-V complex) autoantibodies, which induce Fc-independent signaling and platelet clearance, are refractory to conventional treatment. Protein kinase C (PKC) is activated by the binding of the ligand von Willebrand factor (VWF) to GPIbα and regulates VWF-GPIbα-induced platelet activation. However, the role of PKC in anti-GPIbα antibody-induced thrombocytopenia remains unknown.</div></div><div><h3>Materials and methods</h3><div>The anti-GPIbα antibody-induced PKC activation and its underlying mechanisms were first detected by Western blot, and then the effects of PKC inhibitors, PKC knockout, or GPIbα C-terminal removal on anti-GPIbα antibody-induced platelet apoptosis, activation, aggregation, and clearance were investigated by flow cytometry, platelet aggregometry, and platelet posttransfusion, respectively. Meanwhile, platelet retention and co-localization with macrophages in the liver were detected by spinning disc intravital confocal microscopy.</div></div><div><h3>Results</h3><div>Anti-GPIbα antibody-induced PKC activation depends on GPIbα clustering and phosphoinositide 3-kinase (PI3K) activation and results in Akt phosphorylation. Pharmacologic inhibition or genetic ablation of PKC suppresses anti-GPIbα antibody-induced platelet apoptosis and activation. Moreover, the GPIbα cytoplasmic tail is required for antibody-induced PKC activation, platelet apoptosis, and activation. Inhibition or ablation of PKC and deletion of the GPIbα cytoplasmic tail protect platelets from clearance in vivo.</div></div><div><h3>Conclusions</h3><div>Our study indicates the important role of PKC and the GPIbα cytoplasmic tail in anti-GPIbα antibody-mediated platelet signaling and clearance and suggests a novel therapeutic target for ITP and other thrombocytopenic diseases.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109210"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142628616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased risk of pulmonary embolism in patients with dermatomyositis/polymyositis, a retrospective cohort study from Israel","authors":"Roi Amster ,&nbsp;Abdulla Watad ,&nbsp;Uria Shani ,&nbsp;Dennis McGonagle ,&nbsp;Arnon D. Cohen ,&nbsp;Howard Amital ,&nbsp;Niv Ben-Shabat","doi":"10.1016/j.thromres.2024.109203","DOIUrl":"10.1016/j.thromres.2024.109203","url":null,"abstract":"<div><h3>Background</h3><div>Despite the well-established association between chronic inflammatory conditions and pulmonary embolism(PE), previous investigations of the relationship between Dermatomyositis(DM) and Polymyositis(PM) with PE were scarce and have been subject to significant limitations, including small sample sizes and failure to account for potential confounders.</div></div><div><h3>Objectives</h3><div>To investigate the correlation between DM/PM and PE, as well as assessing the impact of serologic status, myonecrosis, and inflammation markers on this relationship.</div></div><div><h3>Methods</h3><div>In this large, nationwide population-based study, we used the Clalit Health Services medical database and extracted all DM/PM patients who were first diagnosed between 1 January 2002 to 31 December 2018 and compared them with age and gender matched controls in a ratio of 1:5. Serological and laboratory values were obtained for each patient. Rates of PE were compared between groups using multivariate models.</div></div><div><h3>Results</h3><div>The study included 1557 DM patients with 7633 controls, and 528 PM patients with 2560 controls. Compared with matched controls, the rates of PE were significantly higher in the DM/PM group, PM patients(2.8 % vs 0.5 % in controls, OR = 5.73, <em>p</em> &lt; 0.001), DM patients(1.2 % vs 0.3 % in controls, OR = 3.42, <em>p</em> &lt; 0.001). APLA seropositivity was significantly more prevalent in DM/PM patients compared with their matched controls, PM patients(10.8 % vs 2.7 % in controls, <em>p</em> &lt; 0.001), DM patients(7.9 % vs 1.6 % in controls, p &lt; 0.001). APLA seropositivity had a synergistic effect for PE in the DM/PM(OR = 23.18, p &lt; 0.001).</div></div><div><h3>Conclusions</h3><div>DM and PM are associated with higher rates of PE. Furthermore, patients with DM/PM demonstrate a significantly higher prevalence APLA which act as a potentiator of thrombosis in these patients.</div></div>","PeriodicalId":23064,"journal":{"name":"Thrombosis research","volume":"244 ","pages":"Article 109203"},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142605580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}