Journal of Thrombosis and Haemostasis最新文献

{"title":"Incidence and clinical course of chronic thromboembolic pulmonary hypertension with or without a history of venous thromboembolism in Denmark","authors":"Frederikus A. Klok ,&nbsp;Emese Vágó ,&nbsp;Erzsébet Horváth-Puhó ,&nbsp;Stefano Barco ,&nbsp;Asger Andersen ,&nbsp;Kasper Bonnesen ,&nbsp;Anton Vonk-Noordegraaf ,&nbsp;Marion Delcroix ,&nbsp;Stavros V. Konstantinides ,&nbsp;Dieuwke Luijten ,&nbsp;Suzanne C. Cannegieter ,&nbsp;Henrik Toft Sørensen","doi":"10.1016/j.jtha.2024.09.006","DOIUrl":"10.1016/j.jtha.2024.09.006","url":null,"abstract":"<div><h3>Background</h3><div>A considerable number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) lack a history of venous thromboembolism (VTE).</div></div><div><h3>Objectives</h3><div>We aimed to examine the annual incidence and prevalence of CTEPH in Denmark and to compare the rates of VTE, bleeding, and mortality between CTEPH patients with and without a history of VTE.</div></div><div><h3>Methods</h3><div>The Danish National Patient Registry covering all Danish hospitals was used to identify all CTEPH cases between 2009 and 2018, based on combinations of discharge diagnoses using <em>International Classification of Diseases</em>, <em>10th Revision</em> codes for CTEPH and relevant diagnostic and/or therapeutic interventions. Incidence rates of CTEPH per 100 000 person-years, rates of VTE and bleeding, and 5-year survival estimates were calculated.</div></div><div><h3>Results</h3><div>In total, 509 CTEPH patients were identified, of whom 82% had a history of VTE. The yearly incidence rate of CTEPH was 0.5 to 0.8 per 100 000 person-years during the study period. Patients with a history of VTE experienced a 2.5-fold rate of VTE compared with those without prior VTE (2571 vs 980 per 100 000 person-years), while the rate of bleeding events was lower (5008 vs 7139 per 100 000 person-years). The 5-year survival of CTEPH patients with a VTE history was 65% (95% CI, 58%-71%) compared with 45% (95% CI, 31%-58%) in patients without a history of VTE.</div></div><div><h3>Conclusion</h3><div>The Danish incidence rate of CTEPH was comparable with that of other European countries. We identified notable differences in the prognosis of patients with CTEPH with or without a history of VTE. These findings may support generation of hypotheses regarding the pathophysiology of CTEPH and inform current patient care.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3562-3571"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289962","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":"Patency and reflux in relation to postthrombotic syndrome: a subanalysis of the Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome trial","authors":"Ruben D. Hupperetz ,&nbsp;Aaron F.J. Iding ,&nbsp;Jorinde van Laanen ,&nbsp;Rutger Brans ,&nbsp;Pascale Notten ,&nbsp;Lidwine W. Tick ,&nbsp;Louis-Jean Vleming ,&nbsp;Asiong Jie ,&nbsp;Nils Planken ,&nbsp;Cees H.A. Wittens ,&nbsp;Hugo ten Cate ,&nbsp;Arina J. ten Cate-Hoek","doi":"10.1016/j.jtha.2024.08.022","DOIUrl":"10.1016/j.jtha.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Adjunctive catheter-directed thrombolysis shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency.</div></div><div><h3>Objectives</h3><div>This Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome (CAVA) trial subanalysis investigated the effect of ultrasound-accelerated catheter-directed thrombolysis (UACDT) on patency, reflux, and their relevance in PTS development.</div></div><div><h3>Methods</h3><div>This multicenter, randomized, single-blind trial enrolled patients (aged 18-85 years) with a first iliofemoral deep vein thrombosis and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound at 12 months (T12) and long-term (LT) follow-up (median, 39.5 months; IQR, 24.0-63.0 months). PTS was diagnosed using the Villalta score.</div></div><div><h3>Results</h3><div>UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs 25.9% standard treatment [ST]; <em>P</em> = .002) and LT (45.2% UACDT vs 11.9% ST; <em>P</em> &lt; .001). Popliteal patency, however, was similar between groups (87.9% UACDT vs 83.3% ST; <em>P</em> = .487). Reflux was similar between groups at T12 and LT; only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs 44.8% ST; <em>P</em> = .010). Absent iliac patency at T12 was associated with increased PTS risk in the ST group only (odds ratio [OR], 10.84; 95% CI, 1.93-60.78; <em>P</em> = .007). In the UACDT group, popliteal reflux at T12 was associated with moderate-to-severe PTS at T12 (OR, 4.88; 95% CI, 1.10-21.57; <em>P</em> = .041) and LT (OR, 5.83; 95% CI, 1.44-23.63; <em>P</em> = .009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR, 10.79; 95% CI, 2.41-48.42; <em>P</em> &lt; .001).</div></div><div><h3>Conclusion</h3><div>UACDT improved patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-to-severe PTS and contribute synergistically to its development. However, a proportion of moderate-to-severe PTS cases lacks an evident underlying cause.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3552-3561"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289964","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":"Resistance to tPA-induced fibrinolysis and activation of coagulation is present in autoimmune bullous diseases of the skin","authors":"Divya Sharma ,&nbsp;Christopher D. Barrett ,&nbsp;Hunter B. Moore ,&nbsp;Joe H. Jackson ,&nbsp;Tanner M. Sandberg ,&nbsp;Flobater I. Gawargi ,&nbsp;Trace B. Moody ,&nbsp;Xiaoyue Cheng ,&nbsp;Corey J. Georgesen ,&nbsp;Erin X. Wei","doi":"10.1016/j.jtha.2024.08.024","DOIUrl":"10.1016/j.jtha.2024.08.024","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3640-3644"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289965","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":"“Four years into the pandemic, managing COVID-19 patients with acute coagulopathy: what have we learned?” Comment from Wada et al","authors":"Hideo Wada ,&nbsp;Takeshi Matsumoto ,&nbsp;Katsuya Shiraki","doi":"10.1016/j.jtha.2024.08.030","DOIUrl":"10.1016/j.jtha.2024.08.030","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3647-3649"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748501","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":"Assessment of antibodies against platelet factor 4 following vaccination with adenovirus type 26–vectored vaccines","authors":"Hendy Kristyanto ,&nbsp;Leen Slaets ,&nbsp;Esmée Braams ,&nbsp;Ilse Scheys ,&nbsp;Roy Heesbeen ,&nbsp;Vicky Cárdenas ,&nbsp;Georgi Shukarev ,&nbsp;Gert Scheper ,&nbsp;Jerald Sadoff ,&nbsp;Kerstin Lühn ,&nbsp;Hanneke Schuitemaker ,&nbsp;Frank Struyf ,&nbsp;Jenny Hendriks","doi":"10.1016/j.jtha.2024.08.019","DOIUrl":"10.1016/j.jtha.2024.08.019","url":null,"abstract":"<div><h3>Background</h3><div>Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse event identified following vaccination with some adenovirus-vectored COVID-19 vaccines, including Ad26.COV2.S. VITT is characterized by the presence of antibodies against platelet factor 4 (PF4).</div></div><div><h3>Objectives</h3><div>To evaluate whether PF4 antibodies were generally induced following vaccination with adenovirus type 26 (Ad26)–vectored vaccines.</div></div><div><h3>Methods</h3><div>The study included 913 and 991 healthy participants without thromboembolic (TE) events in Ad26.COV2.S and non–COVID-19 Ad26-vectored vaccine clinical studies, respectively, and 1 participant with VITT following Ad26.COV2.S vaccination. PF4 antibody levels were measured in prevaccination and postvaccination sera. PF4 antibody positivity rates were assessed in a case-control setting in participants who developed TE events during participation in Ad26-vectored vaccine clinical studies.</div></div><div><h3>Results</h3><div>In the 1 VITT patient, PF4 antibodies were negative before vaccination. Seroconversion for platelet-activating PF4 antibodies was observed upon Ad26.COV2.S vaccination. In participants without TE events, the PF4 antibody levels and positivity rates were similar before and after Ad26 vaccination. Ad26 vaccination did not increase PF4 antibody levels in participants who were PF4 antibody–positive at baseline (<em>n</em> = 47). Lastly, 1 out of 28 TE cases and 2 out of 156 non-TE controls seroconverted after Ad26.COV2.S vaccination. None of the 15 TE cases and 3 of the 77 non-TE controls seroconverted following non–COVID-19 Ad26 vaccination.</div></div><div><h3>Conclusion</h3><div>Ad26.COV2.S and the other Ad26-vectored vaccines studied did not generally induce PF4 antibodies or increase preexisting PF4 antibody levels. Moreover, unlike VITT, TE events that occurred at any time following Ad26 vaccination were not associated with PF4 antibodies.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3532-3541"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289959","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":"Viral coagulation: pushing the envelope","authors":"Edward Louis George Pryzdial ,&nbsp;John Ruggles Perrier ,&nbsp;Mahamud-Ur Rashid ,&nbsp;Henry Euan West ,&nbsp;Michael Ross Sutherland","doi":"10.1016/j.jtha.2024.08.014","DOIUrl":"10.1016/j.jtha.2024.08.014","url":null,"abstract":"<div><div>Many virus types affect the blood clotting system with correlations to pathology that range widely from thrombosis to hemorrhage linking to inflammation. Here we overview the intricate crosstalk induced by infection between proteins on the virus encoded by either the host or virus genomes, coagulation proteins, platelets, leukocytes, and endothelial cells. For blood-borne viruses with an outer covering acquired from the host cell, the envelope, a key player may be the cell-derived trigger of coagulation on the virus surface, tissue factor (TF). TF is a multifunctional transmembrane cofactor that accelerates factor (F)VIIa–dependent activation of FX to FXa, leading to clot formation. However, the nascent TF/FVIIa/FXa complex also facilitates G protein–coupled modulation of cells via protease-activated receptor 2. As a viral envelope constituent, TF can bypass the physiological modes of regulation, thereby initiating the activation of neighboring platelets, leukocytes, and endothelial cells. A thromboinflammatory environment is predicted due to feedback amplification in response to cellular release of cytokines, procoagulant proteins, neutrophil extracellular traps, and stimulus-induced accessibility of adhesive receptors, resulting in cellular aggregates. The pathobiological effects of thromboinflammation ultimately contribute to innate and adaptive immunity for viral clearance. In contrast, the preceding stages of viral infection may be enhanced via the TF-protease axis.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3366-3382"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289967","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":"HMGB1 in platelets: a viable therapeutic target?","authors":"Sebastian Vogel","doi":"10.1016/j.jtha.2024.09.004","DOIUrl":"10.1016/j.jtha.2024.09.004","url":null,"abstract":"","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3392-3394"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748073","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":"Factors associated with venous thromboembolism pharmacoprophylaxis initiation in hospitalized medical patients: the Medical Inpatients Thrombosis and Hemostasis study","authors":"Allen B. Repp ,&nbsp;Andrew D. Sparks ,&nbsp;Katherine Wilkinson ,&nbsp;Nicholas S. Roetker ,&nbsp;Jordan K. Schaefer ,&nbsp;Ang Li ,&nbsp;Leslie A. McClure ,&nbsp;Deirdra R. Terrell ,&nbsp;Augusto Ferraris ,&nbsp;Alys Adamski ,&nbsp;Nicholas L. Smith ,&nbsp;Neil A. Zakai","doi":"10.1016/j.jtha.2024.08.016","DOIUrl":"10.1016/j.jtha.2024.08.016","url":null,"abstract":"<div><h3>Background</h3><div>Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown.</div></div><div><h3>Objectives</h3><div>To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services.</div></div><div><h3>Methods</h3><div>We performed a cohort study using electronic health record data from adult patients hospitalized on medical services at 4 academic medical centers between 2016 and 2019. Main measures were candidate predictors of HA-VTE pharmacoprophylaxis initiation, including known HA-VTE risk factors, predicted HA-VTE risk, and bleeding diagnoses present on admission.</div></div><div><h3>Results</h3><div>Among 111 550 admissions not on intermediate or full-dose anticoagulation, 48 520 (43.5%) received HA-VTE pharmacoprophylaxis on the day of or the day after admission. After adjustment for age, sex, race/ethnicity, and study site, the strongest clinical predictors of HA-VTE pharmacoprophylaxis initiation were malnutrition and chronic obstructive pulmonary disease. Thrombocytopenia and history of gastrointestinal bleeding were associated with decreased odds of HA-VTE pharmacoprophylaxis initiation. Patients in the highest 2 tertiles of predicted HA-VTE risk were less likely to receive HA-VTE pharmacoprophylaxis than patients in the lowest (first) tertile (OR, 0.84; 95% CI, 0.81-0.86 for the second tertile; OR, 0.95; 95% CI, 0.92-0.98 for the third tertile).</div></div><div><h3>Conclusion</h3><div>Among patients not already receiving anticoagulants, HA-VTE pharmacoprophylaxis initiation during the first 2 hospital days was lower in patients with a higher predicted HA-VTE risk and those with risk factors for bleeding. Reasons for not initiating pharmacoprophylaxis in those with a higher predicted HA-VTE risk could not be assessed.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3521-3531"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142182688","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":"Bivariate genome-wide association study of circulating fibrinogen and C-reactive protein levels","authors":"Julie Hahn ,&nbsp;Gerard Temprano-Sagrera ,&nbsp;Natalie R. Hasbani ,&nbsp;Symen Ligthart ,&nbsp;Abbas Dehghan ,&nbsp;Alisa S. Wolberg ,&nbsp;Nicholas L. Smith ,&nbsp;Maria Sabater-Lleal ,&nbsp;Alanna C. Morrison ,&nbsp;Paul S. de Vries","doi":"10.1016/j.jtha.2024.08.021","DOIUrl":"10.1016/j.jtha.2024.08.021","url":null,"abstract":"<div><h3>Background</h3><div>Fibrinogen and C-reactive protein (CRP) play an important role in inflammatory pathways and share multiple genetic loci reported in previously published genome-wide association studies (GWAS), highlighting their common genetic background. Leveraging the shared biology may identify further loci pleiotropically associated with both fibrinogen and CRP.</div></div><div><h3>Objectives</h3><div>To identify novel genetic variants that are pleiotropic and associated with both fibrinogen and CRP, by integrating both phenotypes in a bivariate GWAS by using a multitrait GWAS.</div></div><div><h3>Methods</h3><div>We performed a bivariate GWAS to identify further pleiotropic genetic loci, using summary statistics of previously published GWAS on fibrinogen (<em>n</em> = 120 246) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium, consisting of European ancestry samples and CRP (<em>n</em> = 363 228) from UK Biobank, including 5 different population groups. The main analysis was performed using metaUSAT and N-GWAMA. We conducted replication for novel CRP associations to test the robustness of the findings using an independent GWAS for CRP (<em>n</em> = 148 164). We also performed colocalization analysis to compare the associations in identified loci for the 2 traits and Genotype-Tissue Expression data.</div></div><div><h3>Results</h3><div>We identified 87 pleiotropic loci that overlapped between metaUSAT and N-GWAMA, including 23 previously known for either fibrinogen or CRP, 58 novel loci for fibrinogen, and 6 novel loci for both fibrinogen and CRP. Overall, there were 30 pleiotropic and novel loci for both traits, and 7 of these showed evidence of colocalization, located in or near <em>ZZZ3</em>, <em>NR1I2</em>, <em>RP11-72L22.</em>1, <em>MICU1</em>, <em>ARL14EP</em>, <em>SOCS2</em>, and <em>PGM5</em>. Among these 30 loci, 13 replicated for CRP in an independent CRP GWAS.</div></div><div><h3>Conclusion</h3><div>Bivariate GWAS identified additional associated loci for fibrinogen and CRP. This analysis suggests fibrinogen and CRP share a common genetic architecture with many pleiotropic loci.</div></div>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":"22 12","pages":"Pages 3448-3459"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142289960","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":"Molecular basis of platelet granule defects.","authors":"Helen Hy Yao, Walter Ha Kahr","doi":"10.1016/j.jtha.2024.11.016","DOIUrl":"https://doi.org/10.1016/j.jtha.2024.11.016","url":null,"abstract":"<p><p>Platelets are small, discoid, anucleate blood cells that play key roles in clotting and other functions involved in health and disease. Platelets are derived from bone marrow-resident megakaryocytes, which undergo a complex developmental process where they increase dramatically in size and produce an abundance of organelles destined for platelets. These organelles include mitochondria, lysosomes, peroxisomes and two unique types of secretory organelle: α and dense (δ) granules. Dense granules contain small molecules including ATP, ADP and serotonin, and ions such as Ca²⁺ and Zn²⁺. α-granules contain a variety of cargo proteins, which when secreted by activated platelets are involved in processes such as hemostasis (e.g. fibrinogen and Von Willebrand factor), angiogenesis, inflammation and wound healing. Investigations of patients with inherited conditions resulting in decreased/abnormal platelet secretory granules have led to the identification of proteins, protein complexes and cellular processes involved in their production by megakaryocytes. Notably, studies of ARPC1B deficiency, Hermansky-Pudlak and Chediak-Higashi syndromes have linked several genes/proteins to dense granule biogenesis. Studies of multisystemic ARC syndrome revealed the requirement of two proteins, VPS33B and VPS16B in α-granule formation. Identification of the genetic cause of gray platelet syndrome established that NBEAL2 is an additional protein needed for α-granule cargo retention. These discoveries enabled studies using animal models, cell culture and molecular analysis to gain insights regarding the roles of proteins and cellular processes involved in platelet secretory granule production, which are discussed in this review.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770203","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}