{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:51:14Z","timestamp":1780487474749,"version":"3.54.1"},"reference-count":170,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T00:00:00Z","timestamp":1639958400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>COVID-19 infection is associated with a broad spectrum of presentations, but alveolar capillary microthrombi have been described as a common finding in COVID-19 patients, appearing as a consequence of a severe endothelial injury with endothelial cell membrane disruption. These observations clearly point to the identification of a COVID-19-associated coagulopathy, which may contribute to thrombosis, multi-organ damage, and cause of severity and fatality. One significant finding that emerges in prothrombotic abnormalities observed in COVID-19 patients is that the coagulation alterations are mainly mediated by the activation of platelets and intrinsically related to viral-mediated endothelial inflammation. Beyond the well-known role in hemostasis, the ability of platelets to also release various potent cytokines and chemokines has elevated these small cells from simple cell fragments to crucial modulators in the blood, including their inflammatory functions, that have a large influence on the immune response during infectious disease. Indeed, platelets are involved in the pathogenesis of acute lung injury also by promoting NET formation and affecting vascular permeability. Specifically, the deposition by activated platelets of the chemokine platelet factor 4 at sites of inflammation promotes adhesion of neutrophils on endothelial cells and thrombogenesis, and it seems deeply involved in the phenomenon of vaccine-induced thrombocytopenia and thrombosis. Importantly, the hyperactivated platelet phenotype along with evidence of cytokine storm, high levels of P-selectin, D-dimer, and, on the other hand, decreased levels of fibrinogen, von Willebrand factor, and thrombocytopenia may be considered suitable biomarkers that distinguish the late stage of COVID-19 progression in critically ill patients.<\/jats:p>","DOI":"10.3390\/ijms222413638","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T08:43:32Z","timestamp":1639989812000},"page":"13638","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Prothrombotic Phenotype in COVID-19: Focus on Platelets"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3201-5883","authenticated-orcid":false,"given":"Cristina","family":"Barale","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, 10043 Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Melchionda","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, 10043 Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8407-2903","authenticated-orcid":false,"given":"Alessandro","family":"Morotti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, 10043 Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2921-1763","authenticated-orcid":false,"given":"Isabella","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, Turin University, 10043 Orbassano, Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2015432","article-title":"Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in COVID-19","volume":"383","author":"Ackermann","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.2217\/fmb.09.112","article-title":"Bacterial-Platelet Interactions: Virulence Meets Host Defense","volume":"5","author":"Yeaman","year":"2010","journal-title":"Future Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1160\/TH14-02-0126","article-title":"The Role of Platelets in Sepsis","volume":"112","year":"2014","journal-title":"Thromb. Haemost."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"286","DOI":"10.3109\/09537104.2015.1010441","article-title":"Platelets in Inflammation and Infection","volume":"26","author":"Jenne","year":"2015","journal-title":"Platelets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"85","DOI":"10.3389\/fimmu.2019.00085","article-title":"Cell Type-Specific Roles of NF-\u039aB Linking Inflammation and Thrombosis","volume":"10","author":"Mussbacher","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Liverani, E., Mondrinos, M.J., Sun, S., Kunapuli, S.P., and Kilpatrick, L.E. (2018). Role of Protein Kinase C-Delta in Regulating Platelet Activation and Platelet-Leukocyte Interaction during Sepsis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195379"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Acanfora, D., Acanfora, C., Ciccone, M.M., Scicchitano, P., Bortone, A.S., Uguccioni, M., and Casucci, G. (2021). The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases. Viruses, 13.","DOI":"10.3390\/v13101904"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/S0024-3205(97)01167-3","article-title":"Linkage between Inflammation and Coagulation: An Update on the Molecular Basis of the Crosstalk","volume":"62","author":"Cicala","year":"1998","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/j.1538-7836.2011.04323.x","article-title":"Innate Immunity and Coagulation","volume":"9","author":"Esmon","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2975","DOI":"10.1161\/ATVBAHA.120.315175","article-title":"Platelets Promote Thromboinflammation in SARS-CoV-2 Pneumonia","volume":"40","author":"Taus","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.pathol.1.110304.100100","article-title":"Inflammation and Atherosclerosis","volume":"1","author":"Hansson","year":"2006","journal-title":"Annu. Rev. Pathol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/s41569-021-00552-1","article-title":"Interplay between Inflammation and Thrombosis in Cardiovascular Pathology","volume":"18","author":"Stark","year":"2021","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/CIRCRESAHA.120.317447","article-title":"The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications","volume":"127","author":"McFadyen","year":"2020","journal-title":"Circ. Res."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Melillo, F., Napolano, A., Loffi, M., Regazzoni, V., Boccellino, A., Danzi, G.B., Cappelletti, A.M., Rovere-Querini, P., Landoni, G., and Ingallina, G. (2021). Myocardial Injury in Patients with SARS-CoV-2 Pneumonia: Pivotal Role of Inflammation in COVID-19. Eur. J. Clin. Investig., e13703.","DOI":"10.1111\/eci.13703"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108255","DOI":"10.1016\/j.intimp.2021.108255","article-title":"The Triumvirate of NF-\u039aB, Inflammation and Cytokine Storm in COVID-19","volume":"101","author":"Attiq","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1182\/blood.2020007214","article-title":"Platelet Gene Expression and Function in Patients with COVID-19","volume":"136","author":"Manne","year":"2020","journal-title":"Blood"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Barrett, T.J., Bilaloglu, S., Cornwell, M., Burgess, H.M., Virginio, V.W., Drenkova, K., Ibrahim, H., Yuriditsky, E., Aphinyanaphongs, Y., and Lifshitz, M. (2021). Platelets Contribute to Disease Severity in COVID-19. J. Thromb. Haemost.","DOI":"10.1161\/circ.144.suppl_1.11039"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1007\/s11239-020-02182-9","article-title":"Profile of Natural Anticoagulant, Coagulant Factor and Anti-Phospholipid Antibody in Critically Ill COVID-19 Patients","volume":"50","author":"Zhang","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical Course and Risk Factors for Mortality of Adult Inpatients with COVID-19 in Wuhan, China: A Retrospective Cohort Study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Comer, S.P., Cullivan, S., Szklanna, P.B., Weiss, L., Cullen, S., Kelliher, S., Smolenski, A., Murphy, C., Altaie, H., and Curran, J. (2021). COVID-19 Induces a Hyperactive Phenotype in Circulating Platelets. PLoS Biol., 19.","DOI":"10.1371\/journal.pbio.3001109"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1161\/CIRCRESAHA.120.317703","article-title":"Platelets Can Associate with SARS-Cov-2 RNA and Are Hyperactivated in COVID-19","volume":"127","author":"Zaid","year":"2020","journal-title":"Circ. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1083\/jcb.201304054","article-title":"The Incredible Journey: From Megakaryocyte Development to Platelet Formation","volume":"201","author":"Machlus","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nature21706","article-title":"The Lung Is a Site of Platelet Biogenesis and a Reservoir for Haematopoietic Progenitors","volume":"544","author":"Caudrillier","year":"2017","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/nri2956","article-title":"Platelets and the Immune Continuum","volume":"11","author":"Semple","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.thromres.2012.11.028","article-title":"Platelet-Leukocyte Crosstalk: Linking Proinflammatory Responses to Procoagulant State","volume":"131","author":"Ghasemzadeh","year":"2013","journal-title":"Thromb. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.thromres.2018.04.007","article-title":"Platelet Activation and Antiplatelet Therapy in Sepsis: A Narrative Review","volume":"166","author":"Wang","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1097\/CCM.0b013e318246b9df","article-title":"Acetyl Salicylic Acid Usage and Mortality in Critically Ill Patients with the Systemic Inflammatory Response Syndrome and Sepsis","volume":"40","author":"Eisen","year":"2012","journal-title":"Crit. Care Med."},{"key":"ref_28","first-page":"782573","article-title":"Outcomes of Severe Sepsis and Septic Shock Patients on Chronic Antiplatelet Treatment: A Historical Cohort Study","volume":"2013","author":"Jaffer","year":"2013","journal-title":"Crit. Care Res. Pr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2341","DOI":"10.1161\/ATVBAHA.110.207522","article-title":"Signaling during Platelet Adhesion and Activation","volume":"30","author":"Li","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.tem.2019.05.003","article-title":"Platelets as Potent Signaling Entities in Type 2 Diabetes Mellitus","volume":"30","author":"Pretorius","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1161\/ATVBAHA.114.303411","article-title":"Targeting Integrin and Integrin Signaling in Treating Thrombosis","volume":"35","author":"Estevez","year":"2015","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s12959-016-0100-6","article-title":"Platelets and Platelet Adhesion Molecules: Novel Mechanisms of Thrombosis and Anti-Thrombotic Therapies","volume":"14","author":"Xu","year":"2016","journal-title":"Thromb. J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1080\/09537104.2017.1353682","article-title":"Clathrin-Mediated Integrin AIIb\u03b23 Trafficking Controls Platelet Spreading","volume":"29","author":"Gao","year":"2018","journal-title":"Platelets"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1182\/bloodadvances.2017007732","article-title":"Fibrin and D-Dimer Bind to Monomeric GPVI","volume":"1","author":"Onselaer","year":"2017","journal-title":"Blood Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1161\/ATVBAHA.111.241067","article-title":"Platelet Glycoprotein VI Dimerization, an Active Process Inducing Receptor Competence, Is an Indicator of Platelet Reactivity","volume":"32","author":"Loyau","year":"2012","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/09537104.2018.1508649","article-title":"Does Fibrin(Ogen) Bind to Monomeric or Dimeric GPVI, or Not at All?","volume":"30","author":"Slater","year":"2019","journal-title":"Platelets"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/jth.13919","article-title":"Platelet Collagen Receptor Glycoprotein VI-Dimer Recognizes Fibrinogen and Fibrin through Their D-Domains, Contributing to Platelet Adhesion and Activation during Thrombus Formation","volume":"16","author":"Induruwa","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1182\/blood-2015-02-629717","article-title":"Platelet Glycoprotein VI Binds to Polymerized Fibrin and Promotes Thrombin Generation","volume":"126","author":"Ollivier","year":"2015","journal-title":"Blood"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Jooss, N.J., De Simone, I., Provenzale, I., Fern\u00e1ndez, D.I., Brouns, S.L.N., Farndale, R.W., Henskens, Y.M.C., Kuijpers, M.J.E., Ten Cate, H., and van der Meijden, P.E.J. (2019). Role of Platelet Glycoprotein VI and Tyrosine Kinase Syk in Thrombus Formation on Collagen-Like Surfaces. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20112788"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"898","DOI":"10.3324\/haematol.2017.182972","article-title":"Immobilized Fibrinogen Activates Human Platelets through Glycoprotein VI","volume":"103","author":"Mangin","year":"2018","journal-title":"Haematologica"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1161\/ATVBAHA.107.150474","article-title":"Cell Adhesion Mechanisms in Platelets","volume":"28","author":"Pleines","year":"2008","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zent, R., and Pozzi, A. (2010). Integrin Structure and Function. Cell-Extracellular Matrix Interactions in Cancer, Springer.","DOI":"10.1007\/978-1-4419-0814-8"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41419-020-03333-9","article-title":"SARS-CoV-2 Infection Is Associated with a pro-Thrombotic Platelet Phenotype","volume":"12","author":"Bongiovanni","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1182\/blood-2015-01-624023","article-title":"P-Selectin Promotes Neutrophil Extracellular Trap Formation in Mice","volume":"126","author":"Etulain","year":"2015","journal-title":"Blood"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1182\/blood.2020007252","article-title":"Platelet Activation and Platelet-Monocyte Aggregate Formation Trigger Tissue Factor Expression in Patients with Severe COVID-19","volume":"136","author":"Hottz","year":"2020","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/rth2.12266","article-title":"The Dual Role of Platelet-Innate Immune Cell Interactions in Thrombo-Inflammation","volume":"4","author":"Rayes","year":"2020","journal-title":"Res. Pr. Thromb. Haemost."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1161\/CIRCRESAHA.108.180273","article-title":"Pathophysiological Levels of Soluble P-Selectin Mediate Adhesion of Leukocytes to the Endothelium through Mac-1 Activation","volume":"103","author":"Woollard","year":"2008","journal-title":"Circ. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1213\/ANE.0000000000005292","article-title":"Aspirin Use Is Associated with Decreased Mechanical Ventilation, Intensive Care Unit Admission, and In-Hospital Mortality in Hospitalized Patients with Coronavirus Disease 2019","volume":"132","author":"Chow","year":"2021","journal-title":"Anesth. Analg."},{"key":"ref_49","unstructured":"(2021). RECOVERY Collaborative Group Aspirin in Patients Admitted to Hospital with COVID-19 (RECOVERY): A Randomised, Controlled, Open-Label, Platform Trial. Lancet."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/s41577-021-00536-9","article-title":"Endothelial Dysfunction and Immunothrombosis as Key Pathogenic Mechanisms in COVID-19","volume":"21","author":"Bonaventura","year":"2021","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.3389\/fimmu.2019.02204","article-title":"The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases","volume":"10","author":"Guo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis","volume":"122","author":"Koupenova","year":"2018","journal-title":"Circ. Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nm.1939","article-title":"Heterotypic Interactions Enabled by Polarized Neutrophil Microdomains Mediate Thromboinflammatory Injury","volume":"15","author":"Hidalgo","year":"2009","journal-title":"Nat. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1182\/blood.V75.3.550.550","article-title":"GMP-140 Mediates Adhesion of Stimulated Platelets to Neutrophils","volume":"75","author":"Hamburger","year":"1990","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1172\/JCI29499","article-title":"Complete Reversal of Acid-Induced Acute Lung Injury by Blocking of Platelet-Neutrophil Aggregation","volume":"116","author":"Zarbock","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1164\/rccm.201108-1533OC","article-title":"Disruption of Platelet-Derived Chemokine Heteromers Prevents Neutrophil Extravasation in Acute Lung Injury","volume":"185","author":"Grommes","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1002\/(SICI)1521-4141(199802)28:02<433::AID-IMMU433>3.0.CO;2-U","article-title":"Stimulation of P-Selectin Glycoprotein Ligand-1 on Mouse Neutrophils Activates Beta 2-Integrin Mediated Cell Attachment to ICAM-1","volume":"28","author":"Blanks","year":"1998","journal-title":"Eur. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"28750","DOI":"10.1074\/jbc.272.45.28750","article-title":"Engagement of P-Selectin Glycoprotein Ligand-1 Enhances Tyrosine Phosphorylation and Activates Mitogen-Activated Protein Kinases in Human Neutrophils","volume":"272","author":"Hidari","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/sj.mn.7800198","article-title":"Platelet Chemokines and Chemokine Receptors: Linking Hemostasis, Inflammation, and Host Defense","volume":"10","author":"Gear","year":"2003","journal-title":"Microcirculation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4020","DOI":"10.1182\/blood.V94.12.4020","article-title":"Platelet Factor 4-Induced Neutrophil-Endothelial Cell Interaction: Involvement of Mechanisms and Functional Consequences Different from Those Elicited by Interleukin-8","volume":"94","author":"Petersen","year":"1999","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1182\/blood-2004-06-2475","article-title":"Heterophilic Interactions of Platelet Factor 4 and RANTES Promote Monocyte Arrest on Endothelium","volume":"105","author":"Koenen","year":"2005","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2573","DOI":"10.1182\/blood-2013-07-516484","article-title":"Synchronized Integrin Engagement and Chemokine Activation Is Crucial in Neutrophil Extracellular Trap-Mediated Sterile Inflammation","volume":"123","author":"Rossaint","year":"2014","journal-title":"Blood"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/j.biocel.2004.12.003","article-title":"Platelet Factor 4: A Chemokine Enigma","volume":"37","author":"Slungaard","year":"2005","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1172\/JCI61303","article-title":"Platelets Induce Neutrophil Extracellular Traps in Transfusion-Related Acute Lung Injury","volume":"122","author":"Caudrillier","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nm.1898","article-title":"Disrupting Functional Interactions between Platelet Chemokines Inhibits Atherosclerosis in Hyperlipidemic Mice","volume":"15","author":"Koenen","year":"2009","journal-title":"Nat. Med."},{"key":"ref_66","first-page":"3450","article-title":"Platelet Depletion and Aspirin Treatment Protect Mice in a Two-Event Model of Transfusion-Related Acute Lung Injury","volume":"119","author":"Looney","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1096\/fj.01-0199com","article-title":"Platelet, but Not Endothelial, P-Selectin Is Critical for Neutrophil-Mediated Acute Postischemic Renal Failure","volume":"15","author":"Singbartl","year":"2001","journal-title":"FASEB J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1549-8719.2001.tb00159.x","article-title":"Mechanisms of Leukocyte Sequestration in Inflamed Lungs","volume":"8","author":"Doerschuk","year":"2001","journal-title":"Microcirculation"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1042\/bj2180725","article-title":"Anticoagulant Activities of Heparin Oligosaccharides and Their Neutralization by Platelet Factor 4","volume":"218","author":"Lane","year":"1984","journal-title":"Biochem. J."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3980","DOI":"10.1016\/S0021-9258(17)35610-7","article-title":"Neutralization of Heparin-Related Saccharides by Histidine-Rich Glycoprotein and Platelet Factor 4","volume":"261","author":"Lane","year":"1986","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1055\/s-0038-1646434","article-title":"Low Molecular Weight Heparin-Catalyzed Inactivation of Factor Xa and Thrombin by Antithrombin III\u2014Effect of Platelet Factor 4","volume":"66","author":"Schoen","year":"1991","journal-title":"Thromb. Haemost."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.bbrc.2003.09.171","article-title":"Platelet Factor 4 Neutralizes Heparan Sulfate-Enhanced Antithrombin Inactivation of Factor Xa by Preventing Interaction(s) of Enzyme with Polysaccharide","volume":"311","author":"Fiore","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/S0021-9258(17)33882-6","article-title":"Human Platelet Factor 4: Purification and Characterization by Affinity Chromatography. Purification of Human Platelet Factor 4","volume":"251","author":"Levine","year":"1976","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"11546","DOI":"10.1016\/S0021-9258(18)33796-7","article-title":"Proteoglycan Carrier of Human Platelet Factor 4. Isolation and Characterization","volume":"257","author":"Huang","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1016\/0304-4165(72)90267-X","article-title":"Characterization of a Chondroitin 4 -Sulfate Proteoglycan Carrier for Heparin Neutralizing Activity (Platelet Factor 4) Released from Human Blood Platelets","volume":"286","author":"Barber","year":"1972","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0049-3848(80)90412-0","article-title":"Binding of Platelet Factor 4 to Cultured Human Umbilical Vein Endothelial Cells","volume":"19","author":"Busch","year":"1980","journal-title":"Thromb. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1172\/JCI111429","article-title":"Acceleration of Thrombin-Antithrombin Complex Formation in Rat Hindquarters via Heparinlike Molecules Bound to the Endothelium","volume":"74","author":"Marcum","year":"1984","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1160\/TH15-01-0062","article-title":"Polyphosphates Form Antigenic Complexes with Platelet Factor 4 (PF4) and Enhance PF4-Binding to Bacteria","volume":"114","author":"Brandt","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1182\/blood-2014-03-559518","article-title":"Binding of Anti-Platelet Factor 4\/Heparin Antibodies Depends on the Thermodynamics of Conformational Changes in Platelet Factor 4","volume":"124","author":"Kreimann","year":"2014","journal-title":"Blood"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1111\/jth.13955","article-title":"Platelets Kill Bacteria by Bridging Innate and Adaptive Immunity via Platelet Factor 4 and Fc\u03b3RIIA","volume":"16","author":"Palankar","year":"2018","journal-title":"J. Thromb. Haemost."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.1182\/blood-2010-08-301424","article-title":"Platelet Factor 4 Binds to Bacteria, [Corrected] Inducing Antibodies Cross-Reacting with the Major Antigen in Heparin-Induced Thrombocytopenia","volume":"117","author":"Krauel","year":"2011","journal-title":"Blood"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1538-7836.2011.04264.x","article-title":"Platelets and the Innate Immune System: Mechanisms of Bacterial-Induced Platelet Activation","volume":"9","author":"Cox","year":"2011","journal-title":"J. Thromb. Haemost."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Zhi, H., Dai, J., Liu, J., Zhu, J., Newman, D.K., Gao, C., and Newman, P.J. (2015). Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin AIIb\u03b23 and Lyn Kinase. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0135738"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1182\/blood-2008-02-142125","article-title":"Identification of FcgammaRIIa as the ITAM-Bearing Receptor Mediating AlphaIIbbeta3 Outside-in Integrin Signaling in Human Platelets","volume":"112","author":"Boylan","year":"2008","journal-title":"Blood"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1161\/ATVBAHA.110.216515","article-title":"Mechanism of Outside-in {alpha}IIb{beta}3-Mediated Activation of Human Platelets by the Colonizing Bacterium, Streptococcus Gordonii","volume":"30","author":"Keane","year":"2010","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/17474086.2019.1636645","article-title":"High-Dose Intravenous Immunoglobulin for the Treatment and Prevention of Heparin-Induced Thrombocytopenia: A Review","volume":"12","author":"Warkentin","year":"2019","journal-title":"Expert Rev. Hematol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/j.jacc.2016.02.073","article-title":"Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review","volume":"67","author":"Salter","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1111\/bjh.15062","article-title":"Haemostasis and Innate Immunity\u2014A Complementary Relationship: A Review of the Intricate Relationship between Coagulation and Complement Pathways","volume":"180","author":"Keragala","year":"2018","journal-title":"Br. J. Haematol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1111\/j.1538-7836.2006.02065.x","article-title":"Blood Platelets Activate the Classical Pathway of Human Complement","volume":"4","author":"Peerschke","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Deravi, N., Ahsan, E., Fathi, M., Hosseini, P., Yaghoobpoor, S., Lotfi, R., Pourbagheri-Sigaroodi, A., and Bashash, D. (2021). Complement Inhibition: A Possible Therapeutic Approach in the Fight against COVID-19. Rev. Med. Virol., e2316.","DOI":"10.1002\/rmv.2316"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/CIRCULATIONAHA.120.048488","article-title":"Immunothrombotic Dysregulation in COVID-19 Pneumonia Is Associated with Respiratory Failure and Coagulopathy","volume":"142","author":"Nicolai","year":"2020","journal-title":"Circulation"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Ahmad, F., Kannan, M., and Ansari, A.W. (2021). Role of SARS-CoV-2 -Induced Cytokines and Growth Factors in Coagulopathy and Thromboembolism. Cytokine Growth Factor Rev.","DOI":"10.1016\/j.cytogfr.2021.10.007"},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Kanduc, D. (2021). From Anti-SARS-CoV-2 Immune Respons.se to the Cytokine Storm via Molecular Mimicry. Antibodies, 10.","DOI":"10.3390\/antib10040036"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrmicro3269","article-title":"Platelets: At the Nexus of Antimicrobial Defence","volume":"12","author":"Yeaman","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1002\/jmv.25685","article-title":"Coronavirus Infections and Immune Responses","volume":"92","author":"Li","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s11239-020-02172-x","article-title":"Potential Role for Tissue Factor in the Pathogenesis of Hypercoagulability Associated with in COVID-19","volume":"50","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Hottz, E.D., Quirino-Teixeira, A.C., Merij, L.B., Pinheiro, M.B.M., Rozini, S.V., Bozza, F.A., and Bozza, P.T. (2021). Platelet-Leukocyte Interactions in the Pathogenesis of Viral Infections. Platelets, 1\u20138.","DOI":"10.1080\/09537104.2021.1952179"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1038\/cmi.2016.1","article-title":"Aberrant Coagulation Causes a Hyper-Inflammatory Response in Severe Influenza Pneumonia","volume":"13","author":"Yang","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/jmv.25767","article-title":"Platelet-to-Lymphocyte Ratio Is Associated with Prognosis in Patients with Coronavirus Disease-19","volume":"92","author":"Qu","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1002\/jmv.23354","article-title":"Review: Viral Infections and Mechanisms of Thrombosis and Bleeding","volume":"84","author":"Goeijenbier","year":"2012","journal-title":"J. Med. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1056\/NEJMoa1702090","article-title":"Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection","volume":"378","author":"Kwong","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1007\/s00415-004-0519-8","article-title":"Large Artery Ischaemic Stroke in Severe Acute Respiratory Syndrome (SARS)","volume":"251","author":"Umapathi","year":"2004","journal-title":"J. Neurol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1136\/bmj.326.7403.1358","article-title":"Haematological Manifestations in Patients with Severe Acute Respiratory Syndrome: Retrospective Analysis","volume":"326","author":"Wong","year":"2003","journal-title":"BMJ"},{"key":"ref_104","first-page":"1843","article-title":"Detection of SARS-CoV-2 in Different Types of Clinical Specimens","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/jth.15156","article-title":"Is There a Role for the ACE2 Receptor in SARS-CoV-2 Interactions with Platelets?","volume":"19","author":"Campbell","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1186\/s13045-020-00954-7","article-title":"SARS-CoV-2 Binds Platelet ACE2 to Enhance Thrombosis in COVID-19","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/jth.12806","article-title":"Platelets: The Unsung Hero of the Immune Response","volume":"13","author":"Koupenova","year":"2015","journal-title":"J. Thromb. Haemost."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/path.1440","article-title":"The Clinical Pathology of Severe Acute Respiratory Syndrome (SARS): A Report from China","volume":"200","author":"Ding","year":"2003","journal-title":"J. Pathol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.ekir.2020.03.024","article-title":"COVID-19 and the Renin-Angiotensin System","volume":"5","author":"Malha","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1161\/HYPERTENSIONAHA.110.163576","article-title":"Inflammation, Immunity, and Hypertension","volume":"57","author":"Harrison","year":"2011","journal-title":"Hypertension"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Dmitrieva, N.I., and Burg, M.B. (2015). Elevated Sodium and Dehydration Stimulate Inflammatory Signaling in Endothelial Cells and Promote Atherosclerosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128870"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1182\/blood.V71.1.1.1","article-title":"Tissue Factor and Hemostasis","volume":"71","author":"Nemerson","year":"1988","journal-title":"Blood"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1161\/ATVBAHA.107.141911","article-title":"Role of the Extrinsic Pathway of Blood Coagulation in Hemostasis and Thrombosis","volume":"27","author":"Mackman","year":"2007","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1161\/ATVBAHA.117.309846","article-title":"Tissue Factor: An Essential Mediator of Hemostasis and Trigger of Thrombosis","volume":"38","author":"Grover","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1055\/s-0038-1657623","article-title":"Regulation of the Tissue Factor Gene","volume":"78","author":"Mackman","year":"1997","journal-title":"Thromb. Haemost."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"28408","DOI":"10.1074\/jbc.M703586200","article-title":"Histone Deacetylase Inhibitors Suppress TF-KappaB-Dependent Agonist-Driven Tissue Factor Expression in Endothelial Cells and Monocytes","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1074\/jbc.M806010200","article-title":"NF-KappaB Transcription Factor P50 Critically Regulates Tissue Factor in Deep Vein Thrombosis","volume":"284","author":"Li","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1111\/j.1538-7836.2009.03368.x","article-title":"The Many Faces of Tissue Factor","volume":"7","author":"Mackman","year":"2009","journal-title":"J. Thromb. Haemost."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1161\/ATVBAHA.120.315547","article-title":"Patients With COVID-19 Have Elevated Levels of Circulating Extracellular Vesicle Tissue Factor Activity That Is Associated with Severity and Mortality-Brief Report","volume":"41","author":"Rosell","year":"2021","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1111\/jth.15451","article-title":"Tissue Factor Upregulation Is Associated with SARS-CoV-2 in the Lungs of COVID-19 Patients","volume":"19","author":"Subrahmanian","year":"2021","journal-title":"J. Thromb. Haemost."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1080\/09537104.2020.1859104","article-title":"Search for SARS-CoV-2 RNA in Platelets from COVID-19 Patients","volume":"32","author":"Bury","year":"2021","journal-title":"Platelets"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1161\/CIRCRESAHA.120.317803","article-title":"Platelet and Vascular Biomarkers Associate with Thrombosis and Death in Coronavirus Disease","volume":"127","author":"Barrett","year":"2020","journal-title":"Circ. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2020.05.032","article-title":"Proteomic and Metabolomic Characterization of COVID-19 Patient Sera","volume":"182","author":"Shen","year":"2020","journal-title":"Cell"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3949\/ccjm.87a.20047","article-title":"COVID-19: Coronavirus Replication, Pathogenesis, and Therapeutic Strategies","volume":"87","author":"Bergmann","year":"2020","journal-title":"Clevel. Clin. J. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"BSR20210611","DOI":"10.1042\/BSR20210611","article-title":"SARS-CoV-2 Spike Protein S1 Induces Fibrin(Ogen) Resistant to Fibrinolysis: Implications for Microclot Formation in COVID-19","volume":"41","author":"Grobbelaar","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Kawase, M., Kataoka, M., Shirato, K., and Matsuyama, S. (2019). Biochemical Analysis of Coronavirus Spike Glycoprotein Conformational Intermediates during Membrane Fusion. J. Virol., 93.","DOI":"10.1128\/JVI.00785-19"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1126\/science.abb9983","article-title":"Site-Specific Glycan Analysis of the SARS-CoV-2 Spike","volume":"369","author":"Watanabe","year":"2020","journal-title":"Science"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Flores-Alanis, A., Sandner-Miranda, L., Delgado, G., Cravioto, A., and Morales-Espinosa, R. (2020). The Receptor Binding Domain of SARS-CoV-2 Spike Protein Is the Result of an Ancestral Recombination between the Bat-CoV RaTG13 and the Pangolin-CoV MP789. BMC Res. Notes, 13.","DOI":"10.1186\/s13104-020-05242-8"},{"key":"ref_130","first-page":"257","article-title":"Free SARS-CoV-2 Spike Protein S1 Particles May Play a Role in the Pathogenesis of COVID-19 Infection","volume":"86","author":"Letarov","year":"2021","journal-title":"Biochemistry"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri3345","article-title":"Thrombosis as an Intravascular Effector of Innate Immunity","volume":"13","author":"Engelmann","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1146\/annurev-physiol-030212-183752","article-title":"Platelets in Lung Biology","volume":"75","author":"Weyrich","year":"2013","journal-title":"Annu. Rev. Physiol."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2759","DOI":"10.1182\/blood-2013-11-462432","article-title":"Emerging Roles for Platelets as Immune and Inflammatory Cells","volume":"123","author":"Morrell","year":"2014","journal-title":"Blood"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1111\/jth.14879","article-title":"What Do Monitoring Platelet Counts in COVID-19 Teach Us?","volume":"18","author":"Thachil","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1016\/S2352-3026(20)30216-7","article-title":"Endotheliopathy in COVID-19-Associated Coagulopathy: Evidence from a Single-Centre, Cross-Sectional Study","volume":"7","author":"Goshua","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_136","first-page":"1623","article-title":"IL-1 Induces Throboxane-A2 (TxA2) in COVID-19 Causing Inflammation and Micro-Thrombi: Inhibitory Effect of the IL-1 Receptor Antagonist (IL-1Ra)","volume":"34","author":"Conti","year":"2020","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"320","DOI":"10.3109\/09537101003735572","article-title":"Effects of Aspirin and NO-Aspirin (NCX 4016) on Platelet Function and Coagulation in Human Endotoxemia","volume":"21","author":"Derhaschnig","year":"2010","journal-title":"Platelets"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Grobler, C., Maphumulo, S.C., Grobbelaar, L.M., Bredenkamp, J.C., Laubscher, G.J., Lourens, P.J., Steenkamp, J., Kell, D.B., and Pretorius, E. (2020). COVID-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0142.v1"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"e276","DOI":"10.1111\/bjh.16950","article-title":"Thrombocytopenia Is Independently Associated with Poor Outcome in Patients Hospitalized for COVID-19","volume":"190","author":"Maquet","year":"2020","journal-title":"Br. J. Haematol"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1111\/jth.14848","article-title":"Thrombocytopenia and Its Association with Mortality in Patients with COVID-19","volume":"18","author":"Yang","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1111\/bjh.16817","article-title":"The Association between Severe COVID-19 and Low Platelet Count: Evidence from 31 Observational Studies Involving 7613 Participants","volume":"190","author":"Jiang","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/labmed\/lmaa067","article-title":"Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes","volume":"52","author":"Zong","year":"2021","journal-title":"Lab. Med."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1007\/s00277-020-04019-0","article-title":"Mechanism of Thrombocytopenia in COVID-19 Patients","volume":"99","author":"Xu","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1080\/10245330400026170","article-title":"Thrombocytopenia in Patients with Severe Acute Respiratory Syndrome (Review)","volume":"10","author":"Yang","year":"2005","journal-title":"Hematology"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3026","DOI":"10.1038\/s41375-021-01332-z","article-title":"An Evidence That SARS-Cov-2\/COVID-19 Spike Protein (SP) Damages Hematopoietic Stem\/Progenitor Cells in the Mechanism of Pyroptosis in Nlrp3 Inflammasome-Dependent Manner","volume":"35","author":"Kucia","year":"2021","journal-title":"Leukemia"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.thromres.2020.06.008","article-title":"Mechanisms Involved in the Development of Thrombocytopenia in Patients with COVID-19","volume":"193","author":"Zhang","year":"2020","journal-title":"Thromb. Res."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0092-8674(01)00477-9","article-title":"Complement-Independent, Peroxide-Induced Antibody Lysis of Platelets in HIV-1-Related Immune Thrombocytopenia","volume":"106","author":"Nardi","year":"2001","journal-title":"Cell"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.1365-2141.1987.tb06920.x","article-title":"Incidence and Mechanism of Neutropenia and Thrombocytopenia in Patients with Human Immunodeficiency Virus Infection","volume":"66","author":"Murphy","year":"1987","journal-title":"Br. J. Haematol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/bjh.16885","article-title":"Delayed-Phase Thrombocytopenia in Patients with Coronavirus Disease 2019 (COVID-19)","volume":"190","author":"Chen","year":"2020","journal-title":"Br. J. Haematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/j.1365-2141.2004.04987.x","article-title":"Assessment of an Immature Platelet Fraction (IPF) in Peripheral Thrombocytopenia","volume":"126","author":"Briggs","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1309\/50H8JYHN9JWCKAM7","article-title":"A Clinical Evaluation of High Fluorescent Platelet Fraction Percentage in Thrombocytopenia","volume":"125","author":"Kickler","year":"2006","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_152","first-page":"451","article-title":"Immature Platelet Fraction: Establishment of a Reference Interval and Diagnostic Measure for Thrombocytopenia","volume":"30","author":"Jung","year":"2010","journal-title":"Korean J. Lab. Med."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"188","DOI":"10.3109\/09537104.2013.793794","article-title":"Mean Platelet Volume Reproducibility and Association with Platelet Activity and Anti-Platelet Therapy","volume":"25","author":"Shah","year":"2014","journal-title":"Platelets"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1538-7836.2009.03584.x","article-title":"Mean Platelet Volume as a Predictor of Cardiovascular Risk: A Systematic Review and Meta-Analysis","volume":"8","author":"Chu","year":"2010","journal-title":"J. Thromb. Haemost."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1159\/000512007","article-title":"The Impact of COVID-19 Disease on Platelets and Coagulation","volume":"88","author":"Wool","year":"2021","journal-title":"Pathobiology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1016\/j.jacc.2008.05.031","article-title":"Role of Reticulated Platelets and Platelet Size Heterogeneity on Platelet Activity after Dual Antiplatelet Therapy with Aspirin and Clopidogrel in Patients with Stable Coronary Artery Disease","volume":"52","author":"Guthikonda","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1055\/s-0039-1695009","article-title":"Transcriptome Analysis of Reticulated Platelets Reveals a Prothrombotic Profile","volume":"119","author":"Bongiovanni","year":"2019","journal-title":"Thromb. Haemost."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1016\/j.jacc.2014.06.1210","article-title":"Association of Immature Platelets with Adverse Cardiovascular Outcomes","volume":"64","author":"Ibrahim","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.thromres.2016.06.002","article-title":"Immature Platelet Fraction Predicts Coagulopathy-Related Platelet Consumption and Mortality in Patients with Sepsis","volume":"144","author":"Muronoi","year":"2016","journal-title":"Thromb. Res."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"e814","DOI":"10.1097\/MD.0000000000000814","article-title":"An Elevated Percentage of Reticulated Platelet Is Associated with Increased Mortality in Septic Shock Patients","volume":"94","author":"Wu","year":"2015","journal-title":"Medicine"},{"key":"ref_161","unstructured":"Dimitrova, E.K. (2021, November 24). Vaxzevria (Previously COVID-19 Vaccine AstraZeneca). Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/vaxzevria-previously-COVID-19-vaccine-astrazeneca."},{"key":"ref_162","unstructured":"(2021, November 24). SARS-CoV-2 Variants of Concern as of 18 November 2021. Available online: https:\/\/www.ecdc.europa.eu\/en\/COVID-19\/variants-concern."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1056\/NEJMoa2104840","article-title":"Thrombotic Thrombocytopenia after ChAdOx1 NCov-19 Vaccination","volume":"384","author":"Greinacher","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.1056\/NEJMoa2104882","article-title":"Thrombosis and Thrombocytopenia after ChAdOx1 NCoV-19 Vaccination","volume":"384","author":"Schultz","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.thromres.2021.12.002","article-title":"SARS-CoV-2 Vaccine-Induced Immune Thrombotic Thrombocytopenia","volume":"209","author":"Liu","year":"2021","journal-title":"Thromb. Res."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1182\/blood.2021012938","article-title":"Anti-Platelet Factor 4 Antibodies Causing VITT Do Not Cross-React with SARS-CoV-2 Spike Protein","volume":"138","author":"Greinacher","year":"2021","journal-title":"Blood"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1160\/TH16-02-0109","article-title":"Risk Factors for Heparin-Induced Thrombocytopenia: Focus on Fc\u03b3 Receptors","volume":"116","author":"Rollin","year":"2016","journal-title":"Thromb. Haemost."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1038\/s41467-019-09160-7","article-title":"Neutrophil Activation and NETosis Are the Major Drivers of Thrombosis in Heparin-Induced Thrombocytopenia","volume":"10","author":"Perdomo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1182\/blood.2020009487","article-title":"Complement Mediates Binding and Procoagulant Effects of Ultralarge HIT Immune Complexes","volume":"138","author":"Khandelwal","year":"2021","journal-title":"Blood"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.7326\/M21-2680","article-title":"Thrombosis After Vaccination with Messenger RNA\u20131273: Is This Vaccine-Induced Thrombosis and Thrombocytopenia or Thrombosis With Thrombocytopenia Syndrome?","volume":"174","author":"Pishko","year":"2021","journal-title":"Ann. Intern. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13638\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:49:39Z","timestamp":1760168979000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13638"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,20]]},"references-count":170,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413638"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413638","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,20]]}}}