Research and Practice in Thrombosis and Haemostasis最新文献

{"title":"Incident thrombocytopenia and bleeding risk in elderly patients with atrial fibrillation on direct oral anticoagulants: insights from the ATHEROsclerosis in Atrial Fibrillation study","authors":"Danilo Menichelli ,&nbsp;Luca Crisanti ,&nbsp;Tommaso Brogi ,&nbsp;Gregory Y.H. Lip ,&nbsp;Alessio Farcomeni ,&nbsp;Pasquale Pignatelli ,&nbsp;Daniele Pastori","doi":"10.1016/j.rpth.2024.102575","DOIUrl":"10.1016/j.rpth.2024.102575","url":null,"abstract":"<div><h3>Background</h3><div>The bleeding risk of patients with atrial fibrillation (AF) changes over time. Most studies thus far evaluated only the baseline bleeding risk with discordant results. The impact of incident thrombocytopenia during direct oral anticoagulant (DOAC) therapy and its relation to bleeding has not been previously investigated.</div></div><div><h3>Objectives</h3><div>To investigate the incidence rate of thrombocytopenia and major bleeding (MB) risk in AF patients on DOACs.</div></div><div><h3>Methods</h3><div>Prospective ongoing ATHEROsclerosis in Atrial Fibrillation study including patients with nonvalvular AF on DOACs. Incident thrombocytopenia was defined as a platelet count &lt;150 × 10⁹/L. MB events were recorded at each follow-up visit. Gray estimator for competing risk data was used. Estimates are expressed in terms of subdistributional hazard ratios (sHR) and relative 95% CI for MB.</div></div><div><h3>Results</h3><div>We enrolled 957 AF patients treated with DOACs (mean age, 77.3 ± 9.0 years; 49.1% women). During a follow-up (median time to censoring 1330 days; 95% CI, 1246-1443), 139 patients developed thrombocytopenia (3.08 per 100 person-years; 95% CI, 2.27-3.89) with no difference between direct thrombin and factor Xa inhibitors. Overall, 179 bleedings occurred, of which 80 were major (3.17 per 100 person-years; 95% CI, 2.34-3.99). Patients sustaining bleedings were more frequently affected by arterial hypertension, heart failure, anemia and had higher CHA₂DS₂-VASc and HAS-BLED scores. On multivariable Cox analysis, independent risk factors for MB were incident thrombocytopenia (sHR, 12.77; 95% CI, 8.880-18.360; <em>P</em> &lt; .001), and age (sHR, 1.030 per year; 95% CI, 1.010-1.040; <em>P</em> = .002).</div></div><div><h3>Conclusion</h3><div>Patients developing thrombocytopenia have an increased risk of MB. Dynamic evaluation of platelet count during follow-up may provide better prognostic value than baseline assessment only.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102575"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419950","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":"Functional characterization of a nanobody-based glycoprotein VI-specific platelet agonist","authors":"Minka Zivkovic ,&nbsp;Elisabeth Pols - van Veen ,&nbsp;Vossa van der Vegte ,&nbsp;Silvie A.E. Sebastian ,&nbsp;Annick S. de Moor ,&nbsp;Suzanne J.A. Korporaal ,&nbsp;Roger E.G. Schutgens ,&nbsp;Rolf T. Urbanus","doi":"10.1016/j.rpth.2024.102582","DOIUrl":"10.1016/j.rpth.2024.102582","url":null,"abstract":"<div><h3>Background</h3><div>Glycoprotein (GP)VI is a platelet-specific collagen receptor required for platelet activation during hemostasis. Platelet reactivity toward collagen is routinely assessed during diagnostic workup of platelet disorders. GPVI can be activated by inducing receptor clustering with suspensions of fibrillar collagen or synthetic cross-linked collagen-related peptide (CRP-XL). However, these suspensions are poorly standardized or difficult to produce. Nanobodies are small recombinant camelid-derived heavy-chain antibody variable regions. They are highly stable, specific, and ideal candidates for developing a stable GPVI agonist for diagnostic assays.</div></div><div><h3>Objectives</h3><div>Develop a stable nanobody-based GPVI agonist.</div></div><div><h3>Methods</h3><div>Nanobody D2 (NbD2) was produced as dimers and purified. Tetramers were generated via C-terminal fusion of dimers with click chemistry. Nanobody constructs were functionally characterized with light transmission aggregometry (LTA) in platelet-rich plasma and whole blood flow cytometry. Diagnostic performance was assessed in patients with inherited platelet function disorders with LTA and flow cytometry.</div></div><div><h3>Results</h3><div>NbD2 was specific for human platelet GPVI. Dimers did not result in platelet activation in LTA or flow cytometry settings and fully inhibited CRP-XL-induced P-selectin expression and fibrinogen binding in whole blood and attenuated collagen-induced platelet aggregation in platelet-rich plasma. However, NbD2 tetramers caused full platelet aggregation, as well as P-selectin expression and fibrinogen binding. NbD2 tetramers were able to discriminate between inherited platelet function disorder patients and healthy controls based on fibrinogen binding, similar to CRP-XL.</div></div><div><h3>Conclusion</h3><div>Nanobody tetramers to GPVI induce platelet activation and can be used to assess the GPVI pathway in diagnostic assays.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102582"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535137","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":"Great white sighting: a case of heparin-induced thrombosis with thrombocytosis","authors":"Julia Levy ,&nbsp;Hong De Sa ,&nbsp;Lindsey Loss ,&nbsp;Mandy VanSandt ,&nbsp;Rhusheet Patel ,&nbsp;Merav Sendowski","doi":"10.1016/j.rpth.2024.102587","DOIUrl":"10.1016/j.rpth.2024.102587","url":null,"abstract":"<div><h3>Background</h3><div>Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse response to heparin therapy, characterized by decreased platelet count and increased risk of thrombosis. HIT, without the tell-tale sign of thrombocytopenia, has rarely been described.</div></div><div><h3>Key Clinical Question</h3><div>Can HIT be diagnosed in the presence of thrombocytosis? What clinical clues and diagnostic tools facilitate accurate diagnosis in such cases?</div></div><div><h3>Clinical Approach</h3><div>We report a case of HIT with thrombocytosis in a young male who initially presented after traumatic knee dislocation. HIT was diagnosed clinically through the discovery of a white thrombus during a vascular surgery procedure and corroborated by a positive latex immunoturbidimetric immunoassay (HemosIL HIT-Ab _{(platelet-factor 4(PF4)-heparin)}), a rapid immunoassay.</div></div><div><h3>Conclusion</h3><div>With its high sensitivity, specificity, and rapid results, the latex immunoturbidimetric immunoassay is a valuable diagnostic tool, even among patients with a seemingly low pretest probability. This case underscores the guidance imparted by Dr Andreas Greinacher: “[HIT] must be considered if thrombosis occurs or progresses despite effective heparinization even in the absence of thrombocytopenia.” Access to rapid and effective laboratory testing reduces the probability of diagnostic error.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102587"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142552331","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 impact of pulmonary embolism on health outcomes of COVID-19 at 3 months after hospitalization","authors":"Chantal Visser ,&nbsp;Julia C. Berentschot ,&nbsp;Cindy M.M. de Jong ,&nbsp;M. Louisa Antoni ,&nbsp;L. Martine Bek ,&nbsp;Rita J.G. van den Berg-Emons ,&nbsp;Bram van den Borst ,&nbsp;Hugo ten Cate ,&nbsp;Arina J. ten Cate-Hoek ,&nbsp;Dionne C.W. Braeken ,&nbsp;J.J. Miranda Geelhoed ,&nbsp;Majanka H. Heijenbrok-Kal ,&nbsp;Sander M.J. van Kuijk ,&nbsp;Lucia J.M. Kroft ,&nbsp;Jenneke Leentjens ,&nbsp;Anna H.E. Roukens ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Frederikus A. Klok ,&nbsp;Marieke J.H.A. Kruip ,&nbsp;Merel E. Hellemons","doi":"10.1016/j.rpth.2024.102573","DOIUrl":"10.1016/j.rpth.2024.102573","url":null,"abstract":"<div><h3>Background</h3><div>COVID-19 patients frequently experience pulmonary embolism (PE), but its long-term consequences remain uncertain.</div></div><div><h3>Objectives</h3><div>To assess the impact of PE in COVID-19 patients on health outcomes at 3 months after hospitalization.</div></div><div><h3>Methods</h3><div>In this multicenter cross-sectional study, we aggregated data from existing databases to evaluate the impact of PE on health outcomes at 3 months after hospitalization. We assessed 1) questionnaires on health-related quality of life (5-level EuroQol 5-dimensional questionnaire [EQ-5D-5L] questionnaire), anxiety, depression, cognitive failure, and posttraumatic stress disorder; 2) pulmonary function tests (diffusing capacity of the lungs for carbon monoxide [DLCO] and spirometry); and 3) radiological abnormalities. We developed 3 models to assess the association between PE and the EQ-5D-5L index and the percentage of predicted DLCO (DLCO%): a crude model (model 1), adjusted for age, sex, and presence of comorbidities (model 2), and model 2 additionally adjusted for intensive care unit admission (model 3).</div></div><div><h3>Results</h3><div>We included 465 patients who had been hospitalized for COVID-19, of whom 102 (21.9%) had developed a PE during admission. Patients with PE had poorer EQ-5D-5L index values, more impairment in pulmonary functions, and more frequent radiological abnormalities than patients without PE. Symptoms of anxiety, depression, cognitive failure, and posttraumatic stress disorder did not differ between the 2 groups. In model 2, PE was associated with lower EQ-5D-5L index and lower DLCO%. After additionally adjusting for intensive care unit admission, the association between PE and lower EQ-5D-5L index (mean difference = −0.069, [95% CI, −0.12 to −0.017]) remained but not between PE and DLCO%.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that PE in COVID-19 patients is associated with reduced health-related quality of life at 3 months after hospitalization. While PE may be a marker of COVID-19 severity, its presence during hospitalization could indicate potential long-term health issues, which may be considered during follow-up care.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102573"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419949","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":"Periprocedural hemostatic prophylaxis and outcomes in bleeding disorder of unknown cause","authors":"Callie Berkowitz ,&nbsp;Alice Ma ,&nbsp;Vanessa Miller ,&nbsp;Supreet Goraya ,&nbsp;Kristi Kirkland ,&nbsp;Julie Grabell ,&nbsp;Nigel S. Key ,&nbsp;Paula D. James","doi":"10.1016/j.rpth.2024.102572","DOIUrl":"10.1016/j.rpth.2024.102572","url":null,"abstract":"<div><h3>Background</h3><div>Bleeding disorder of unknown cause (BDUC) is a diagnostic category encompassing patients with a clear bleeding phenotype but without identifiable abnormality on hemostatic testing. The optimal management of hemostasis in BDUC patients prior to invasive procedures and childbirth is uncertain.</div></div><div><h3>Objectives</h3><div>Our objective was to characterize periprocedural hemostatic prophylaxis and bleeding outcomes in patients with BDUC.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of adult patients with BDUC at 2 academic medical centers. Following diagnosis of BDUC, subsequent surgical procedures and childbirths were analyzed using a combination of registry data and manual chart review.</div></div><div><h3>Results</h3><div>We identified 127 patients with mean age of 39.9 years (SD = 16.6); the majority of patients were female (91.3%). Forty-eight major procedures, 70 minor procedures, and 19 childbirths were analyzed. Antifibrinolytic monotherapy was advised for 57% of major procedures, 59% of minor procedures, and 67% of childbirths. Perioperative platelet transfusion was recommended in 26% of major procedures and 9% of minor procedures in combination with other hemostatic agents. Major or clinically relevant nonmajor bleeding occurred in 4.1% (4/98) of procedures with prophylaxis and 10% (2/20) of procedures without prophylaxis. Postpartum hemorrhage occurred in 26% (5/19) of deliveries.</div></div><div><h3>Conclusion</h3><div>In this multiinstitution experience, we found overall low rates of hemostatic complications in procedures completed with hemostatic prophylaxis, although preventing hemorrhage in childbirth and gynecologic procedures remain unmet needs.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102572"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535135","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":"Prediction of the chance of successful immune tolerance induction in persons with severe hemophilia A and inhibitors: a clinical prediction model","authors":"Ilja Oomen ,&nbsp;Amal Abdi ,&nbsp;Ricardo M. Camelo ,&nbsp;Fábia M.R.A. Callado ,&nbsp;Luany E.M. Carvalho ,&nbsp;Ilenia L. Calcaterra ,&nbsp;Manuel Carcao ,&nbsp;Giancarlo Castaman ,&nbsp;Jeroen C.J. Eikenboom ,&nbsp;Kathelijn Fischer ,&nbsp;Vivian K.B. Franco ,&nbsp;Martijn W. Heymans ,&nbsp;Frank W.G. Leebeek ,&nbsp;David Lillicrap ,&nbsp;Cláudia S. Lorenzato ,&nbsp;Maria Elisa Mancuso ,&nbsp;Davide Matino ,&nbsp;Matteo N.D. Di Minno ,&nbsp;Alex B. Mohseny ,&nbsp;Johannes Oldenburg ,&nbsp;Samantha C. Gouw","doi":"10.1016/j.rpth.2024.102580","DOIUrl":"10.1016/j.rpth.2024.102580","url":null,"abstract":"<div><h3>Background</h3><div>Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI. Estimating the individual chance of ITI success allows clinicians, patients, and their families to support shared decision-making.</div></div><div><h3>Objectives</h3><div>We aimed to identify clinical predictors of ITI success and to develop a clinical prediction model to estimate the chance of successful ITI in persons with severe HA.</div></div><div><h3>Methods</h3><div>This multicenter study included persons with severe HA who received ITI. Clinical data were collected. Successful ITI was defined by a negative inhibitor titer and an adequate response to FVIII concentrates. A multivariable logistic regression model was developed. Model performance and internal validation were performed.</div></div><div><h3>Results</h3><div>Of 206 participants with a median age of 19.8 months (IQR, 12.1-38.8) at ITI start, 148 (71.8%) achieved ITI success. Our clinical prediction model included 4 predictors of ITI success: cumulative number of FVIII exposure days at inhibitor development, peak inhibitor titer, ethnicity, and <em>F8</em> mutation type. The C statistic was 0.801 (95% CI, 0.70-0.87).</div></div><div><h3>Conclusion</h3><div>In our study, including 206 people with severe HA and inhibitors, we developed a clinical prediction model to estimate the chance of successful ITI. After future external validation, this clinical prediction model may be useful for informing clinicians and families.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102580"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592790","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":"Reported particles are not blood clots, so anticoagulant drugs are not a plausible treatment","authors":"Tilly Fox ,&nbsp;Beverley Hunt ,&nbsp;Alan Carson ,&nbsp;Katie Scandrett ,&nbsp;George Davey Smith ,&nbsp;Paul Garner ,&nbsp;Rebecca Kuehn","doi":"10.1016/j.rpth.2024.102598","DOIUrl":"10.1016/j.rpth.2024.102598","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102598"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142654131","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":"Mathematical modeling identifies clotting factor combinations that modify thrombin generation in normal and factor VIII-, IX-, or XI-deficient blood","authors":"Michael T. Stobb ,&nbsp;Keith B. Neeves ,&nbsp;Dougald M. Monroe ,&nbsp;Suzanne S. Sindi ,&nbsp;Karin Leiderman ,&nbsp;Aaron L. Fogelson","doi":"10.1016/j.rpth.2024.102570","DOIUrl":"10.1016/j.rpth.2024.102570","url":null,"abstract":"<div><h3>Background</h3><div>In healthy individuals, plasma levels of clotting proteins naturally vary within a range of 50% to 150% of their mean values. We do not know how these variations modify thrombin generation.</div></div><div><h3>Objectives</h3><div>To assess the impact of protein level variations on simulated thrombin generation in normal and factor (F)VIII-, FIX-, or FXI-deficient blood.</div></div><div><h3>Methods</h3><div>We used a mathematical model of flow-mediated coagulation to simulate thrombin generation with all possible combinations of clotting protein variations within the normal range and for various tissue factor levels. We selected, analyzed, and ranked combinations that enhanced thrombin generation compared with baseline.</div></div><div><h3>Results</h3><div>Protein variations most strongly affected thrombin generation at intermediate tissue factor levels. Low tissue factor levels prevented coagulation initiation, while high tissue factor levels always triggered thrombin generation. At intermediate levels, we identified protein variations that substantially modified thrombin generation. Low-normal FV shortened lag times and increased thrombin generation, whereas high-normal FV lengthened lag times and reduced thrombin generation. With severe FVIII and FIX deficiencies, low-normal tissue factor pathway inhibitor α and antithrombin amplified the effect of low-normal FV. For moderate FVIII and FIX deficiencies, high-normal tissue factor pathway inhibitor α and antithrombin enhanced the impact of high-normal FV in reducing thrombin production. In normal and FXI-deficient blood, high-normal FVIII and FIX significantly boosted thrombin generation.</div></div><div><h3>Conclusion</h3><div>Our mathematical model predicted how variations in clotting protein levels, within the normal range, could contribute to the variability of bleeding phenotypes observed with clotting factor deficiencies. Our study generated experimentally testable hypotheses that could aid in developing new therapies toward normal hemostasis.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102570"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419947","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":"Fibrinaloid microclots in long COVID: assessing the actual evidence properly","authors":"Douglas B. Kell ,&nbsp;M. Asad Khan ,&nbsp;Etheresia Pretorius","doi":"10.1016/j.rpth.2024.102566","DOIUrl":"10.1016/j.rpth.2024.102566","url":null,"abstract":"","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102566"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142419951","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":"Loss of endogenous Nox2-NADPH oxidase does not prevent age-induced platelet activation and arterial thrombosis in mice","authors":"Azaj Ahmed ,&nbsp;Gokul Patil ,&nbsp;Vijay K. Sonkar ,&nbsp;Melissa Jensen ,&nbsp;Jennifer Streeter ,&nbsp;Sanjana Dayal","doi":"10.1016/j.rpth.2024.102597","DOIUrl":"10.1016/j.rpth.2024.102597","url":null,"abstract":"<div><h3>Background</h3><div>Reactive oxygen species are known to contribute to platelet hyperactivation and thrombosis during aging; however, the mechanistic contribution of the specific oxidative pathway remains elusive.</div></div><div><h3>Objectives</h3><div>We hypothesized that during aging, endogenous Nox2-NADPH oxidase contributes to platelet reactive oxygen species accumulation and that loss of Nox2 will protect from platelet activation and thrombosis.</div></div><div><h3>Methods</h3><div>We studied littermates of Nox2 knockout (Nox2-KO) and -wild-type (Nox2-WT) mice at young (3-4 months) and old (18-20 months) age. Within platelets, we examined the expression of subunits of NADPH oxidase and enzyme activity, oxidant levels, activation markers, aggregation, and secretion. We also assessed susceptibility to <em>in vivo</em> thrombosis in 2 experimental models.</div></div><div><h3>Results</h3><div>While aged Nox2-WT mice displayed increased mRNA levels for Nox2, aged Nox2-KO mice showed an increase in Nox4 mRNA. However, neither the protein levels of several subunits nor the activity of NADPH oxidase were found to be altered by age or genotype. Both aged Nox2-WT and aged Nox2-KO mice exhibited similar enhancement in levels of platelet oxidants, granule release, α_IIbβ₃ activation, annexin V binding, aggregation and secretion, and a greater susceptibility to platelet-induced pulmonary thrombosis compared with young mice. In a photochemical injury model, adoptive transfer of platelets from aged Nox2-WT or Nox2-KO mice to the aged host mice resulted in a similar time to develop occlusive thrombus in the carotid artery. These findings suggest that loss of endogenous Nox2 does not protect against age-related platelet activation and arterial thrombosis in mice.</div></div><div><h3>Conclusion</h3><div>We conclude that Nox2 is not an essential mediator of prothrombotic effects associated with aging.</div></div>","PeriodicalId":20893,"journal":{"name":"Research and Practice in Thrombosis and Haemostasis","volume":"8 7","pages":"Article 102597"},"PeriodicalIF":3.4,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653540","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}