{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T15:53:21Z","timestamp":1792166001810,"version":"4.4.0"},"reference-count":180,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T00:00:00Z","timestamp":1731283200000},"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>Paroxysmal Nocturnal Hemoglobinuria (PNH) constitutes a rare bone marrow failure syndrome characterized by hemolytic anemia, thrombotic events (TEs), and bone marrow aplasia of variable degrees. Thrombosis is one of the major clinical manifestations of the disease, affecting up to 40% of individuals with PNH. Venous thrombosis is more prevalent, affecting mainly unusual sites, such as intrabdominal and hepatic veins. TEs might be the first clinical manifestation of PNH. Complement activation, endothelial dysfunction, hemolysis, impaired bioavailability of nitric oxide, and activation of platelets and neutrophils are implicated in the pathogenesis of TEs in PNH patients. Moreover, a vicious cycle involving the coagulation cascade, complement system, and inflammation cytokines, such as interleukin-6, is established. Complement inhibitors, such as eculizumab and ravulizumab (C5 inhibitors), have revolutionized the care of patients with PNH. C5 inhibitors should be initiated in patients with PNH and thrombosis, while they constitute a great prophylactic measure for TEs in those individuals. Anticoagulants, such as warfarin and low-molecular-weight heparin, and, in selected cases, direct oral anticoagulants (DOACs) should be used in combination with C5 inhibitors in patients who develop TEs. Novel complement inhibitors are considered an alternative treatment option, especially for those who develop extravascular or breakthrough hemolysis when terminal inhibitors are administered.<\/jats:p>","DOI":"10.3390\/ijms252212104","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:01:27Z","timestamp":1731312087000},"page":"12104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH): From Pathogenesis to Treatment"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1635-7309","authenticated-orcid":false,"given":"Styliani","family":"Kokoris","sequence":"first","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antri","family":"Polyviou","sequence":"additional","affiliation":[{"name":"Department of Hematology and Lymphoma, BMT Unit, Evangelismos General Hospital, 10676 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1783-5111","authenticated-orcid":false,"given":"Paschalis","family":"Evangelidis","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisavet","family":"Grouzi","sequence":"additional","affiliation":[{"name":"Department of Transfusion Service and Clinical Hemostasis, \u201cSaint Savvas\u201d Oncology Hospital, 11522 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1034-6510","authenticated-orcid":false,"given":"Serena","family":"Valsami","sequence":"additional","affiliation":[{"name":"Hematology Laboratory-Blood Bank, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantinos","family":"Tragiannidis","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyri","family":"Gialeraki","sequence":"additional","affiliation":[{"name":"Laboratory of Hematology and Blood Bank Unit, \u201cAttikon\u201d University General Hospital, Medical School, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3135-4630","authenticated-orcid":false,"given":"Dimitrios A.","family":"Tsakiris","sequence":"additional","affiliation":[{"name":"Department of Hemostasis and Thrombosis, University of Basel, 4001 Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-8208","authenticated-orcid":false,"given":"Eleni","family":"Gavriilaki","sequence":"additional","affiliation":[{"name":"Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1182\/blood-2014-02-522128","article-title":"Paroxysmal Nocturnal Hemoglobinuria","volume":"124","author":"Brodsky","year":"2014","journal-title":"Blood"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.3324\/haematol.2017.177618","article-title":"The Prothrombotic State in Paroxysmal Nocturnal Hemoglobinuria: A Multifaceted Source","volume":"103","author":"Macrae","year":"2018","journal-title":"Haematologica"},{"key":"ref_3","first-page":"512","article-title":"Detection of Subclinical\/Minor PNH Clone(S) in Patients with Thrombotic Events","volume":"13","author":"Anastasopoulou","year":"2022","journal-title":"J. Blood Disord. Transfus."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1182\/blood-2005-04-1717","article-title":"Diagnosis and Management of Paroxysmal Nocturnal Hemoglobinuria","volume":"106","author":"Parker","year":"2005","journal-title":"Blood"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e345","DOI":"10.1097\/HS9.0000000000000345","article-title":"Allogeneic Hematopoietic Cell Transplantation in Patients With Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Clones: Time for a Change","volume":"4","author":"Gavriilaki","year":"2020","journal-title":"Hemasphere"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/asheducation-2016.1.208","article-title":"Update on the Diagnosis and Management of Paroxysmal Nocturnal Hemoglobinuria","volume":"2016","author":"Parker","year":"2016","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1172\/JCI136094","article-title":"Complementopathies and Precision Medicine","volume":"130","author":"Gavriilaki","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1111\/bjh.17753","article-title":"How We(\u2019ll) Treat Paroxysmal Nocturnal Haemoglobinuria: Diving into the Future","volume":"196","author":"Risitano","year":"2022","journal-title":"Br. J. Haematol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"100074","DOI":"10.1016\/j.tru.2021.100074","article-title":"Thrombosis and Paroxysmal Nocturnal Haemoglobinuria","volume":"5","author":"Gris","year":"2021","journal-title":"Thromb. Update"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1002\/ccr3.342","article-title":"Anticoagulant Therapy with Rivaroxaban in a Young Patient with Paroxysmal Nocturnal Hemoglobinuria","volume":"3","author":"Dragoni","year":"2015","journal-title":"Clin. Case Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s12959-018-0181-5","article-title":"Antithrombotic Therapy with Rivaroxaban in Five Patients with Paroxysmal Nocturnal Haemoglobinuria and Thrombotic Events","volume":"16","author":"Dragoni","year":"2018","journal-title":"Thromb. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"929","DOI":"10.3324\/haematol.2022.281780","article-title":"Phase II Trials of Zilucoplan in Paroxysmal Nocturnal Hemoglobinuria","volume":"109","author":"Kulasekararaj","year":"2023","journal-title":"Haematologica"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa2029073","article-title":"Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria","volume":"384","author":"Hillmen","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"101158","DOI":"10.1016\/j.blre.2023.101158","article-title":"Paroxysmal Nocturnal Hemoglobinuria: Review of the Patient Experience and Treatment Landscape","volume":"64","author":"Waheed","year":"2024","journal-title":"Blood Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40164-021-00249-8","article-title":"Role of the Lectin Pathway of Complement in Hematopoietic Stem Cell Transplantation-Associated Endothelial Injury and Thrombotic Microangiopathy","volume":"10","author":"Gavriilaki","year":"2021","journal-title":"Exp. Hematol. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Gavriilaki, M., Kimiskidis, V.K., and Gavriilaki, E. (2020). Precision Medicine in Neurology: The Inspirational Paradigm of Complement Therapeutics. Pharmaceuticals, 13.","DOI":"10.3390\/ph13110341"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1182\/blood.2019003863","article-title":"Complement Activity and Complement Regulatory Gene Mutations Are Associated with Thrombosis in APS and CAPS","volume":"135","author":"Chaturvedi","year":"2020","journal-title":"Blood"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1080\/17474086.2024.2348662","article-title":"What Is the Role of Complement in Bystander Hemolysis? Old Concept, New Insights","volume":"17","author":"Evangelidis","year":"2024","journal-title":"Expert Rev. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/s41409-024-02362-8","article-title":"Hemostasis and Complement in Allogeneic Hematopoietic Stem Cell Transplantation: Clinical Significance of Two Interactive Systems","volume":"59","author":"Tsakiris","year":"2024","journal-title":"Bone Marrow Transplant."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1080\/10245332.2018.1444563","article-title":"Renal Involvement in Paroxysmal Nocturnal Hemoglobinuria: An Update on Clinical Features, Pathophysiology and Treatment","volume":"23","author":"Kokoris","year":"2018","journal-title":"Hematology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"523","DOI":"10.3324\/haematol.2009.017848","article-title":"Paroxysmal Nocturnal Hemoglobinuria and Eculizumab","volume":"95","author":"Luzzatto","year":"2010","journal-title":"Haematologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1182\/blood-2012-09-311381","article-title":"Thrombosis in Paroxysmal Nocturnal Hemoglobinuria","volume":"121","author":"Hill","year":"2013","journal-title":"Blood"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S0140-6736(95)12360-1","article-title":"Paroxysmal Nocturnal Haemoglobinuria: Long-Term Follow-up and Prognostic Factors","volume":"348","author":"Mary","year":"1996","journal-title":"Lancet"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3099","DOI":"10.1182\/blood-2008-01-133918","article-title":"Paroxysmal Nocturnal Hemoglobinuria: Natural History of Disease Subcategories","volume":"112","author":"Mary","year":"2008","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1007\/s00277-020-04052-z","article-title":"Baseline Clinical Characteristics and Disease Burden in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Updated Analysis from the International PNH Registry","volume":"99","author":"Schrezenmeier","year":"2020","journal-title":"Ann. Hematol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/ejh.13059","article-title":"Screening and Diagnostic Clinical Algorithm for Paroxysmal Nocturnal Hemoglobinuria: Expert Consensus","volume":"101","author":"Maciejewski","year":"2018","journal-title":"Eur. J. Haematol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1182\/asheducation-2008.1.93","article-title":"Paroxysmal Nocturnal Hemoglobinuria: An Historical Overview","volume":"2008","author":"Parker","year":"2008","journal-title":"Hematology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1182\/hematology.2021000245","article-title":"When Does a PNH Clone Have Clinical Significance?","volume":"2021","author":"Babushok","year":"2021","journal-title":"Hematology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3587","DOI":"10.1182\/blood-2003-01-0009","article-title":"Primary Prophylaxis with Warfarin Prevents Thrombosis in Paroxysmal Nocturnal Hemoglobinuria (PNH)","volume":"102","author":"Hall","year":"2003","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chatzileontiadou, S., Hatjiharissi, E., Angelopoulou, M., Asimakopoulos, J.V., Loutsidi, N.E., Chatzikonstantinou, T., Zikos, P., Bouchla, A., Bezirgiannidou, Z., and Kouvata, E. (2023). Thromboembolic Events in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Real World Data of a Greek Nationwide Multicenter Retrospective Study. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1128994"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1159\/000022532","article-title":"Paroxysmal Nocturnal Hemoglobinuria and the Risk of Venous Thrombosis: Review and Recommendations for Management of the Pregnant and Nonpregnant Patient","volume":"30","author":"Ray","year":"2000","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4123","DOI":"10.1182\/blood-2007-06-095646","article-title":"Effect of the Complement Inhibitor Eculizumab on Thromboembolism in Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"110","author":"Hillmen","year":"2007","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1002\/ajh.24278","article-title":"Impact of Eculizumab Treatment on Paroxysmal Nocturnal Hemoglobinuria: A Treatment versus No-Treatment Study","volume":"91","author":"Loschi","year":"2016","journal-title":"Am. J. Hematol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1097\/01.md.0000126763.68170.46","article-title":"Clinical Course and Flow Cytometric Analysis of Paroxysmal Nocturnal Hemoglobinuria in the United States and Japan","volume":"83","author":"Nishimura","year":"2004","journal-title":"Medicine"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1111\/j.1365-2141.2004.04992.x","article-title":"Natural History of Paroxysmal Nocturnal Haemoglobinuria Using Modern Diagnostic Assays","volume":"126","author":"Moyo","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s12185-013-1346-4","article-title":"Clinical Signs and Symptoms Associated with Increased Risk for Thrombosis in Patients with Paroxysmal Nocturnal Hemoglobinuria from a Korean Registry","volume":"97","author":"Lee","year":"2013","journal-title":"Int. J. Hematol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"922","DOI":"10.3324\/haematol.2013.093161","article-title":"Baseline Characteristics and Disease Burden in Patients in the International Paroxysmal Nocturnal Hemoglobinuria Registry","volume":"99","author":"Schrezenmeier","year":"2014","journal-title":"Haematologica"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1007\/s00277-023-05269-4","article-title":"Relationship of Paroxysmal Nocturnal Hemoglobinuria (PNH) Granulocyte Clone Size to Disease Burden and Risk of Major Vascular Events in Untreated Patients: Results from the International PNH Registry","volume":"102","author":"Dingli","year":"2023","journal-title":"Ann. Hematol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"92411","DOI":"10.18632\/oncotarget.21361","article-title":"Polymorphism of the ABO Gene Associate with Thrombosis Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"8","author":"Long","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1007\/s00277-019-03770-3","article-title":"Prediction of Thrombosis Risk in Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"98","author":"Huang","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1111\/j.1365-2141.2010.08230.x","article-title":"Thrombophilic Screening in Patients with Paroxysmal Nocturnal Haemoglobinuria: A Pilot Study","volume":"150","author":"Dragoni","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_42","first-page":"428","article-title":"Thrombotic Complications in Paroxysmal Nocturnal Haemoglobinuria: A Literature Review","volume":"10","author":"Malato","year":"2012","journal-title":"Blood Transfus."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Fattizzo, B., Serpenti, F., Giannotta, J.A., and Barcellini, W. (2021). Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties. J. Clin. Med., 10.","DOI":"10.3390\/jcm10050948"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1111\/ejh.12543","article-title":"Pathophysiology, Diagnosis, and Treatment of Paroxysmal Nocturnal Hemoglobinuria: A Review","volume":"95","author":"Devalet","year":"2015","journal-title":"Eur. J. Haematol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Beckmann, L., Faizy, T.D., Flottmann, F., Fiehler, J., Bokemeyer, C., Well, L., Beitzen-Heineke, A., and Langer, F. (2024). Multisite Thrombosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria. Hamostaseologie.","DOI":"10.1055\/a-2231-5277"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1182\/blood.V108.11.979.979","article-title":"High Definition Contrast-Enhanced MR Imaging in Paroxysmal Nocturnal Hemoglobinuria (PNH) Suggests a High Frequency of Subclinical Thrombosis","volume":"108","author":"Hill","year":"2006","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"347","DOI":"10.2174\/157016108785909742","article-title":"Thrombosis in Paroxysmal Nocturnal Hemoglobinuria at a Glance: A Clinical Review","volume":"6","author":"Ziakas","year":"2008","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.jhep.2009.06.019","article-title":"Paroxysmal Nocturnal Hemoglobinuria in Budd-Chiari Syndrome: Findings from a Cohort Study","volume":"51","author":"Hoekstra","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1160\/TH07-11-0664","article-title":"Temporal Trends in Mortality Rates from Visceral Vein Thrombosis in Paroxysmal Nocturnal Haemoglobinuria: An Optimistic View","volume":"99","author":"Poulou","year":"2008","journal-title":"Thromb. Haemost."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1160\/TH07-04-0316","article-title":"Stroke in Paroxysmal Nocturnal Haemoglobinuria: Patterns of Disease and Outcome","volume":"98","author":"Poulou","year":"2007","journal-title":"Thromb. Haemost."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Barcellini, W., Scola, E., Lanfranconi, S., Grottaroli, M., Binda, F., Fattizzo, B., Zaninoni, A., Valcamonica, G., Cinnante, C.M., and Boschetti, C. (2018). Paroxysmal Nocturnal Hemoglobinuria (Pnh): Brain Mri Ischemic Lesions In Neurologically Asymtomatic Patients. Sci. Rep., 8.","DOI":"10.1038\/s41598-017-18936-0"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1111\/j.1365-2141.2007.06522.x","article-title":"Purpura Fulminans in Paroxysmal Nocturnal Haemoglobinuria","volume":"137","author":"Watt","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1111\/jocd.13746","article-title":"Lip Necrosis in a Patient with Paroxysmal Nocturnal Hemoglobinuria: Can It Be Triggered by COVID-19?","volume":"19","author":"Elibol","year":"2020","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1056\/NEJM199511093331904","article-title":"Natural History of Paroxysmal Nocturnal Hemoglobinuria","volume":"333","author":"Hillmen","year":"1995","journal-title":"N. Engl. J. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1111\/j.1365-2141.2012.09166.x","article-title":"Under-Recognized Complications in Patients with Paroxysmal Nocturnal Haemoglobinuria: Raised Pulmonary Pressure and Reduced Right Ventricular Function","volume":"158","author":"Hill","year":"2012","journal-title":"Br. J. Haematol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1007\/s00415-005-0871-3","article-title":"Cerebral Ischemic Infarction in Paroxysmal Nocturnal Hemoglobinuria Report of 2 Cases and Updated Review of 7 Previously Published Patients","volume":"252","author":"Audebert","year":"2005","journal-title":"J. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/1477-9560-2-10","article-title":"Thromboembolic Events and Haematological Diseases: A Case of Stroke as Clinical Onset of a Paroxysmal Nocturnal Haemoglobinuria","volume":"2","author":"Granata","year":"2004","journal-title":"Thromb. J."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1007\/s00415-003-1071-7","article-title":"Cerebral Arterial Thrombosis in Paroxysmal Nocturnal Hemoglobinuria","volume":"250","author":"Berkefeld","year":"2003","journal-title":"J. Neurol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12959-021-00269-8","article-title":"JAK2V617F Positive Polycythemia Vera with Paroxysmal Nocturnal Hemoglobinuria and Visceral Thromboses: A Case Report and Review of the Literature","volume":"19","author":"Chatzidavid","year":"2021","journal-title":"Thromb. J."},{"key":"ref_60","first-page":"3","article-title":"Prevalence of Small PNH Clones and Their Prognostic Significance in Patients Tested for Unusual Indications: A Single Center Experience","volume":"185","author":"Fattizzo","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Giannotta, J.A., Fattizzo, B., and Barcellini, W. (2021). Paroxysmal Nocturnal Hemoglobinuria in the Context of a Myeloproliferative Neoplasm: A Case Report and Review of the Literature. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.756589"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1111\/j.1365-2141.1995.tb05371.x","article-title":"Activated Platelets in Paroxysmal Nocturnal Haemoglobinuria","volume":"91","author":"Gralnick","year":"1995","journal-title":"Br. J. Haematol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.cell.2009.11.001","article-title":"Platelet Polyphosphates Are Proinflammatory and Procoagulant Mediators in Vivo","volume":"139","author":"Mutch","year":"2009","journal-title":"Cell"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1182\/blood.V82.4.1192.1192","article-title":"Complement-Induced Vesiculation and Exposure of Membrane Prothrombinase Sites in Platelets of Paroxysmal Nocturnal Hemoglobinuria","volume":"82","author":"Wiedmer","year":"1993","journal-title":"Blood"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5873","DOI":"10.1073\/pnas.84.16.5873","article-title":"Regulation of the Activity of Platelet-Bound C3 Convertase of the Alternative Pathway of Complement by Platelet Factor H","volume":"84","author":"Devine","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1182\/blood.V68.4.875.875","article-title":"Complement Proteins C5b-9 Stimulate Procoagulant Activity through Platelet Prothrombinase","volume":"68","author":"Wiedmer","year":"1986","journal-title":"Blood"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1172\/JCI112773","article-title":"Interactions of the Platelets in Paroxysmal Nocturnal Hemoglobinuria with Complement. Relationship to Defects in the Regulation of Complement and to Platelet Survival in Vivo","volume":"79","author":"Devine","year":"1987","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3451","DOI":"10.1182\/blood.V93.10.3451.410k27_3451_3456","article-title":"Elevated Levels of Circulating Procoagulant Microparticles in Patients with Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia","volume":"93","author":"Hugel","year":"1999","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1172\/JCI108648","article-title":"Mechanism of Complement-Mediated Activation of Human Blood Platelets in Vitro: Comparison of Normal and Paroxysmal Nocturnal Hemoglobinuria Platelets","volume":"59","author":"Dixon","year":"1977","journal-title":"J. Clin. Investig."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.blre.2009.04.001","article-title":"Platelet Alpha-Granules: Basic Biology and Clinical Correlates","volume":"23","author":"Blair","year":"2009","journal-title":"Blood Rev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18424","DOI":"10.1016\/S0021-9258(19)36980-7","article-title":"Regulation of Glycoprotein IIb-IIIa Receptor Function Studied with Platelets Permeabilized by the Pore-Forming Complement Proteins C5b-9","volume":"267","author":"Shattil","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"S27","DOI":"10.1016\/j.thromres.2012.02.025","article-title":"Microparticles as a Circulating Source of Procoagulant and Fibrinolytic Activities in the Circulation","volume":"129","author":"Lacroix","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"18205","DOI":"10.1016\/S0021-9258(19)81346-7","article-title":"Complement Proteins C5b-9 Cause Release of Membrane Vesicles from the Platelet Surface That Are Enriched in the Membrane Receptor for Coagulation Factor Va and Express Prothrombinase Activity","volume":"263","author":"Sims","year":"1988","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17261","DOI":"10.1016\/S0021-9258(19)47368-7","article-title":"Platelet-Derived Microparticles Express High Affinity Receptors for Factor VIII","volume":"266","author":"Gilbert","year":"1991","journal-title":"J. Biol. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nm.2184","article-title":"Reciprocal Coupling of Coagulation and Innate Immunity via Neutrophil Serine Proteases","volume":"16","author":"Massberg","year":"2010","journal-title":"Nat. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1080\/09537105310001657110","article-title":"The Platelet Function Defect of Paroxysmal Nocturnal Haemoglobinuria","volume":"15","author":"Schmid","year":"2004","journal-title":"Platelets"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"17049","DOI":"10.1016\/S0021-9258(18)71457-9","article-title":"Assembly of the Platelet Prothrombinase Complex Is Linked to Vesiculation of the Platelet Plasma Membrane","volume":"264","author":"Sims","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1161\/01.CIR.96.10.3534","article-title":"Cell-Derived Microparticles Generated in Patients during Cardiopulmonary Bypass Are Highly Procoagulant","volume":"96","author":"Nieuwland","year":"1997","journal-title":"Circulation"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1111\/j.1365-2141.2004.04974.x","article-title":"Elevated Circulating Endothelial Membrane Microparticles in Paroxysmal Nocturnal Haemoglobinuria","volume":"125","author":"Simak","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1124\/jpet.103.058883","article-title":"Reversibility versus Persistence of GPIIb\/IIIa Blocker-Induced Conformational Change of GPIIb\/IIIa (AlphaIIbbeta3, CD41\/CD61)","volume":"308","author":"Schwarz","year":"2004","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1084\/jem.20041497","article-title":"Platelet Activation Leads to Activation and Propagation of the Complement System","volume":"201","author":"Zhang","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_82","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_83","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1111\/j.1538-7836.2008.03034.x","article-title":"Complement Activation Triggered by Chondroitin Sulfate Released by Thrombin Receptor-Activated Platelets","volume":"6","author":"Hamad","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"6367","DOI":"10.1182\/bloodadvances.2023010817","article-title":"Complement and Platelets: Prothrombotic Cell Activation Requires Membrane Attack Complex-Induced Release of Danger Signals","volume":"7","author":"Mannes","year":"2023","journal-title":"Blood Adv."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6364","DOI":"10.1182\/bloodadvances.2023011186","article-title":"ADP: The Missing Link between Thrombosis and Hemolysis","volume":"7","author":"Gerber","year":"2023","journal-title":"Blood Adv."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"23304","DOI":"10.3402\/jev.v3.23304","article-title":"The Central Role of Extracellular Vesicles in the Mechanisms of Thrombosis in Paroxysmal Nocturnal Haemoglobinuria: A Review","volume":"3","author":"Devalet","year":"2014","journal-title":"J. Extracell. Vesicles"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e94","DOI":"10.3324\/haematol.2018.198846","article-title":"Significant Hemolysis Is Not Required for Thrombosis in Paroxysmal Nocturnal Hemoglobinuria","volume":"104","author":"Griffin","year":"2019","journal-title":"Haematologica"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"100834","DOI":"10.1016\/j.blre.2021.100834","article-title":"It Takes Two to Thrombosis: Hemolysis and Complement","volume":"50","author":"Jongerius","year":"2021","journal-title":"Blood Rev."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1001\/jama.293.13.1653","article-title":"The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin: A Novel Mechanism of Human Disease","volume":"293","author":"Rother","year":"2005","journal-title":"JAMA"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/bjh.13183","article-title":"New Perspectives on the Thrombotic Complications of Haemolysis","volume":"168","author":"Hod","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1161\/01.CIR.93.2.327","article-title":"Enhancement of Platelet Deposition by Cross-Linked Hemoglobin in a Rat Carotid Endarterectomy Model","volume":"93","author":"Olsen","year":"1996","journal-title":"Circulation"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S0002-9343(88)80092-5","article-title":"Thrombophlebitis and Disturbed Hemostasis Following Administration of Intravenous Hematin in Normal Volunteers","volume":"85","author":"Simionatto","year":"1988","journal-title":"Am. J. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1160\/TH08-10-0677","article-title":"Haemoglobin Blocks von Willebrand Factor Proteolysis by ADAMTS-13: A Mechanism Associated with Sickle Cell Disease","volume":"101","author":"Zhou","year":"2009","journal-title":"Thromb. Haemost."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Papakonstantinou, A., Kalmoukos, P., Mpalaska, A., Koravou, E.-E., and Gavriilaki, E. (2024). ADAMTS13 in the New Era of TTP. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25158137"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1182\/blood-2013-04-495887","article-title":"Heme Triggers TLR4 Signaling Leading to Endothelial Cell Activation and Vaso-Occlusion in Murine Sickle Cell Disease","volume":"123","author":"Belcher","year":"2014","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.exphem.2007.12.003","article-title":"Oxidative Status of Red Blood Cells, Neutrophils, and Platelets in Paroxysmal Nocturnal Hemoglobinuria","volume":"36","author":"Amer","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1432-1033.1994.tb18782.x","article-title":"Role of Hydroxyl Radicals in the Activation of Human Platelets","volume":"221","author":"Iuliano","year":"1994","journal-title":"Eur. J. Biochem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2141.2007.06740.x","article-title":"Beta-Thalassaemia and Sickle Cell Anaemia as Paradigms of Hypercoagulability","volume":"139","author":"Ataga","year":"2007","journal-title":"Br. J. Haematol."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Hopp, M.-T., and Imhof, D. (2021). Linking Labile Heme with Thrombosis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10030427"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"15880","DOI":"10.1073\/pnas.1005743107","article-title":"Extracellular DNA Traps Promote Thrombosis","volume":"107","author":"Fuchs","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2768","DOI":"10.1182\/blood-2013-10-463646","article-title":"Thrombosis: Tangled up in NETs","volume":"123","author":"Martinod","year":"2014","journal-title":"Blood"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1046\/j.1365-2141.1999.01483.x","article-title":"Complement-Induced Procoagulant Alteration of Red Blood Cell Membranes with Microvesicle Formation in Paroxysmal Nocturnal Haemoglobinuria (PNH): Implication for Thrombogenesis in PNH","volume":"106","author":"Ninomiya","year":"1999","journal-title":"Br. J. Haematol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1111\/j.1365-2141.2010.08505.x","article-title":"Procoagulant Properties of Microparticles Released from Red Blood Cells in Paroxysmal Nocturnal Haemoglobinuria","volume":"152","author":"Kozuma","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tmrv.2005.08.001","article-title":"Cell Membrane Microparticles in Blood and Blood Products: Potentially Pathogenic Agents and Diagnostic Markers","volume":"20","author":"Simak","year":"2006","journal-title":"Transfus. Med. Rev."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1182\/blood.V90.7.2716","article-title":"Apoptosis Resistance of Blood Cells from Patients with Paroxysmal Nocturnal Hemoglobinuria, Aplastic Anemia, and Myelodysplastic Syndrome","volume":"90","author":"Horikawa","year":"1997","journal-title":"Blood"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1182\/blood.V81.2.510.510","article-title":"Cells Lacking Glycan Phosphatidylinositol-Linked Proteins Have Impaired Ability to Vesiculate","volume":"81","author":"Whitlow","year":"1993","journal-title":"Blood"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1161\/ATVBAHA.123.318780","article-title":"Basic Mechanisms of Hemolysis-Associated Thrombo-Inflammation and Immune Dysregulation","volume":"43","author":"Dimitrov","year":"2023","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00277-004-0856-9","article-title":"Evidence for a Metabolic Shift of Arginine Metabolism in Sickle Cell Disease","volume":"83","author":"Schnog","year":"2004","journal-title":"Ann. Hematol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1097\/00043426-200011000-00009","article-title":"Patterns of Arginine and Nitric Oxide in Patients with Sickle Cell Disease with Vaso-Occlusive Crisis and Acute Chest Syndrome","volume":"22","author":"Morris","year":"2000","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"17028","DOI":"10.1038\/nrdp.2017.28","article-title":"Paroxysmal Nocturnal Haemoglobinuria","volume":"3","author":"Hill","year":"2017","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1182\/blood.V98.6.1802","article-title":"Heme Is a Potent Inducer of Inflammation in Mice and Is Counteracted by Heme Oxygenase","volume":"98","author":"Wagener","year":"2001","journal-title":"Blood"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1182\/blood-2010-01-267112","article-title":"The Critical Roles of Platelet Activation and Reduced NO Bioavailability in Fatal Pulmonary Arterial Hypertension in a Murine Hemolysis Model","volume":"116","author":"Hu","year":"2010","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/nm1674","article-title":"Rapid Conditional Targeted Ablation of Cells Expressing Human CD59 in Transgenic Mice by Intermedilysin","volume":"14","author":"Hu","year":"2008","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1681\/ASN.V12102088","article-title":"Protective Role of Nitric Oxide in a Model of Thrombotic Microangiopathy in Rats","volume":"12","author":"Shao","year":"2001","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1111\/j.1365-2141.2010.08096.x","article-title":"Effect of Eculizumab on Haemolysis-Associated Nitric Oxide Depletion, Dyspnoea, and Measures of Pulmonary Hypertension in Patients with Paroxysmal Nocturnal Haemoglobinuria","volume":"149","author":"Hill","year":"2010","journal-title":"Br. J. Haematol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1078\/0940-2993-00321","article-title":"Ocular Expression of Vascular Cell Adhesion Molecule (VCAM-1) in 2-Butoxyethanol-Induced Hemolysis and Thrombosis in Female Rats","volume":"55","author":"Nyska","year":"2003","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s00204-003-0471-x","article-title":"2-Butoxyethanol Enhances the Adherence of Red Blood Cells","volume":"77","author":"Koshkaryev","year":"2003","journal-title":"Arch. Toxicol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"456","DOI":"10.3181\/00379727-216-44197","article-title":"Heme Induces the Expression of Adhesion Molecules ICAM-1, VCAM-1, and E Selectin in Vascular Endothelial Cells","volume":"216","author":"Wagener","year":"1997","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"2338","DOI":"10.1182\/blood-2015-05-648030","article-title":"Free Hemoglobin Increases von Willebrand Factor-Mediated Platelet Adhesion in Vitro: Implications for Circulatory Devices","volume":"126","author":"Da","year":"2015","journal-title":"Blood"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.blre.2006.09.001","article-title":"Circulating Microparticles: Pathophysiology and Clinical Implications","volume":"21","author":"Piccin","year":"2007","journal-title":"Blood Rev."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"574","DOI":"10.3324\/haematol.2009.016121","article-title":"Evaluation of Hemostasis and Endothelial Function in Patients with Paroxysmal Nocturnal Hemoglobinuria Receiving Eculizumab","volume":"95","author":"Helley","year":"2010","journal-title":"Haematologica"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s12288-021-01445-6","article-title":"Circulating Endothelial Progenitor Cells and Their Relation to Thrombosis in Paroxysmal Nocturnal Hemoglobinuria and Aplastic Anemia","volume":"38","author":"Erkek","year":"2022","journal-title":"Indian J. Hematol. Blood Transfus."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1155\/2009\/504294","article-title":"SuPAR: The Molecular Crystal Ball","volume":"27","author":"Macho","year":"2009","journal-title":"Dis. Markers"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1538-7836.2011.04562.x","article-title":"Mechanisms and Clinical Implications of Thrombosis in Paroxysmal Nocturnal Hemoglobinuria","volume":"10","author":"Muus","year":"2012","journal-title":"J. Thromb. Haemost."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1097\/00001721-200310000-00011","article-title":"Plasmatic Coagulation and Fibrinolytic System Alterations in PNH: Relation to Clone Size","volume":"14","author":"Siegemund","year":"2003","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1681\/ASN.2020060829","article-title":"Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI","volume":"31","author":"Azam","year":"2020","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1616","DOI":"10.1016\/j.exphem.2008.06.016","article-title":"Increased Soluble Urokinase Plasminogen Activator Receptor (SuPAR) Is Associated with Thrombosis and Inhibition of Plasmin Generation in Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients","volume":"36","author":"Sloand","year":"2008","journal-title":"Exp. Hematol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"e025198","DOI":"10.1161\/JAHA.122.025198","article-title":"Soluble Urokinase Plasminogen Activator Receptor and Venous Thromboembolism in COVID-19","volume":"11","author":"Luo","year":"2022","journal-title":"J. Am. Heart Assoc."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1080\/09537100120068170","article-title":"The Platelet Release Reaction: Granules\u2019 Constituents, Secretion and Functions","volume":"12","author":"Rendu","year":"2001","journal-title":"Platelets."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1111\/j.1538-7836.2006.01873.x","article-title":"A GPI-Anchored Co-Receptor for Tissue Factor Pathway Inhibitor Controls Its Intracellular Trafficking and Cell Surface Expression","volume":"4","author":"Maroney","year":"2006","journal-title":"J. Thromb. Haemost."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.transci.2007.12.001","article-title":"Expression of Tissue Factor Pathway Inhibitor by Endothelial Cells and Platelets","volume":"38","author":"Maroney","year":"2008","journal-title":"Transfus. Apher. Sci."},{"key":"ref_132","first-page":"373","article-title":"The Role of C5a in Interleukin-6 Production Induced by Lipopolysaccharide or Interleukin-1","volume":"74","author":"Montz","year":"1991","journal-title":"Immunology"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1084\/jem.168.1.443","article-title":"C5a Stimulates Secretion of Tumor Necrosis Factor from Human Mononuclear Cells in Vitro. Comparison with Secretion of Interleukin 1 Beta and Interleukin 1 Alpha","volume":"168","author":"Okusawa","year":"1988","journal-title":"J. Exp. Med."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1046\/j.1365-2141.2001.03061.x","article-title":"Interleukin 6 and Haemostasis","volume":"115","author":"Kerr","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1111\/j.1538-7836.2008.02989.x","article-title":"Inflammatory Cytokines Inhibit ADAMTS13 Synthesis in Hepatic Stellate Cells and Endothelial Cells","volume":"6","author":"Cao","year":"2008","journal-title":"J. Thromb. Haemost."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1182\/blood-2012-02-412080","article-title":"Thrombin Generates Previously Unidentified C5 Products That Support the Terminal Complement Activation Pathway","volume":"120","author":"Krisinger","year":"2012","journal-title":"Blood"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/MOH.0000000000000605","article-title":"The Interaction between the Complement System and Hemostatic Factors","volume":"27","author":"Oncul","year":"2020","journal-title":"Curr. Opin. Hematol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the Absence of C3: A New Complement Activation Pathway","volume":"12","author":"Sarma","year":"2006","journal-title":"Nat. Med."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.4049\/jimmunol.177.7.4794","article-title":"A Novel C5a Receptor-Tissue Factor Cross-Talk in Neutrophils Links Innate Immunity to Coagulation Pathways","volume":"177","author":"Ritis","year":"2006","journal-title":"J. Immunol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.thromres.2012.04.001","article-title":"Eculizumab Therapy Results in Rapid and Sustained Decreases in Markers of Thrombin Generation and Inflammation in Patients with PNH Independent of Its Effects on Hemolysis and Microparticle Formation","volume":"130","author":"Weitz","year":"2012","journal-title":"Thromb. Res."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"5927","DOI":"10.4081\/hr.2015.5927","article-title":"Long Standing Eculizumab Treatment without Anticoagulant Therapy in High-Risk Thrombogenic Paroxysmal Nocturnal Hemoglobinuria","volume":"7","author":"AlDallal","year":"2015","journal-title":"Hematol. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/2040620716681748","article-title":"Management of Thrombosis in Paroxysmal Nocturnal Hemoglobinuria: A Clinician\u2019s Guide","volume":"8","author":"Griffin","year":"2017","journal-title":"Ther. Adv. Hematol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1182\/blood.2019003812","article-title":"How I Treat Paroxysmal Nocturnal Hemoglobinuria","volume":"137","author":"Brodsky","year":"2021","journal-title":"Blood"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1111\/j.1365-2141.2011.08690.x","article-title":"Management of Paroxysmal Nocturnal Haemoglobinuria: A Personal View","volume":"153","author":"Luzzatto","year":"2011","journal-title":"Br. J. Haematol."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1182\/blood-2018-09-876136","article-title":"Ravulizumab (ALXN1210) vs Eculizumab in Adult Patients with PNH Naive to Complement Inhibitors: The 301 Study","volume":"133","author":"Lee","year":"2019","journal-title":"Blood"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"101041","DOI":"10.1016\/j.blre.2023.101041","article-title":"Biomarkers and Laboratory Assessments for Monitoring the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria: Differences between Terminal and Proximal Complement Inhibition","volume":"59","author":"Kulasekararaj","year":"2023","journal-title":"Blood Rev."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1056\/NEJMoa1311084","article-title":"Genetic Variants in C5 and Poor Response to Eculizumab","volume":"370","author":"Nishimura","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"371","DOI":"10.47102\/annals-acadmedsg.202475","article-title":"Consensus Recommendations for Optimising the Diagnosis and Treatment of Paroxysmal Nocturnal Haemoglobinuria in Singapore","volume":"53","author":"Goh","year":"2024","journal-title":"Ann. Acad. Med. Singap."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ajh.21506","article-title":"Successful Discontinuation of Anticoagulation Following Eculizumab Administration in Paroxysmal Nocturnal Hemoglobinuria","volume":"84","author":"Emadi","year":"2009","journal-title":"Am. J. Hematol."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3324\/haematol.10516","article-title":"The Risk of Recurrent Venous Thromboembolism after Discontinuing Anticoagulation in Patients with Acute Proximal Deep Vein Thrombosis or Pulmonary Embolism. A Prospective Cohort Study in 1626 Patients","volume":"92","author":"Prandoni","year":"2007","journal-title":"Haematologica"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/VHRM.S197732","article-title":"Splanchnic Vein Thrombosis: Current Perspectives","volume":"15","author":"Valeriani","year":"2019","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1046\/j.1538-7836.2003.00045.x","article-title":"Are Patients with Paroxysmal Nocturnal Hemoglobinuria at Risk for Heparin-Induced Thrombocytopenia?","volume":"1","author":"Huehn","year":"2003","journal-title":"J. Thromb. Haemost."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"344","DOI":"10.3324\/haematol.2011.049767","article-title":"Thrombolytic Therapy Is Effective in Paroxysmal Nocturnal Hemoglobinuria: A Series of Nine Patients and a Review of the Literature","volume":"97","author":"Araten","year":"2012","journal-title":"Haematologica"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"613","DOI":"10.2147\/JBM.S431493","article-title":"Paroxysmal Nocturnal Hemoglobinuria: Current Management, Unmet Needs, and Recommendations","volume":"14","author":"Oliver","year":"2023","journal-title":"J. Blood Med."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1200\/JCO.22.00710","article-title":"Clinical and Molecular Determinants of Clonal Evolution in Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria","volume":"41","author":"Gurnari","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/ejh.13783","article-title":"Long-Term Safety and Efficacy of Ravulizumab in Patients with Paroxysmal Nocturnal Hemoglobinuria: 2-Year Results from Two Pivotal Phase 3 Studies","volume":"109","author":"Kulasekararaj","year":"2022","journal-title":"Eur. J. Haematol."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1182\/blood.2023021762","article-title":"Treatment Outcomes of Complement Protein C5 Inhibition in 509 UK Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"143","author":"Kelly","year":"2024","journal-title":"Blood"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3324\/haematol.2019.236877","article-title":"Characterization of Breakthrough Hemolysis Events Observed in the Phase 3 Randomized Studies of Ravulizumab versus Eculizumab in Adults with Paroxysmal Nocturnal Hemoglobinuria","volume":"106","author":"Brodsky","year":"2021","journal-title":"Haematologica"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1182\/blood.2021012860","article-title":"Advancing Therapeutic Complement Inhibition in Hematologic Diseases: PNH and Beyond","volume":"139","author":"Gavriilaki","year":"2022","journal-title":"Blood"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"425","DOI":"10.2147\/JBM.S361863","article-title":"Low Rate of Clinically Evident Extravascular Hemolysis in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated with a Complement C5 Inhibitor: Results from a Large, Multicenter, US Real-World Study","volume":"13","author":"Shammo","year":"2022","journal-title":"J. Blood Med."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"102416","DOI":"10.1016\/j.rpth.2024.102416","article-title":"Thrombosis and Meningococcal Infection Rates in Pegcetacoplan-Treated Patients with Paroxysmal Nocturnal Hemoglobinuria in the Clinical Trial and Postmarketing Settings","volume":"8","author":"Kelly","year":"2024","journal-title":"Res. Pr. Thromb. Haemost."},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1002\/ajh.27242","article-title":"Real-World Experience of Pegcetacoplan in Paroxysmal Nocturnal Hemoglobinuria","volume":"99","author":"Griffin","year":"2024","journal-title":"Am. J. Hematol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.1007\/s12325-024-02827-8","article-title":"Safety and Efficacy of Pegcetacoplan in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria over 48 Weeks: 307 Open-Label Extension Study","volume":"41","author":"Patriquin","year":"2024","journal-title":"Adv. Ther."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"2329030","DOI":"10.1080\/16078454.2024.2329030","article-title":"Expert Consensus on the Management of Pharmacodynamic Breakthrough-Hemolysis in Treated Paroxysmal Nocturnal Hemoglobinuria","volume":"29","author":"Dingli","year":"2024","journal-title":"Hematology"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/ijlh.14281","article-title":"Complement Inhibition in Paroxysmal Nocturnal Hemoglobinuria: From Biology to Therapy","volume":"46","author":"Versino","year":"2024","journal-title":"Int. J. Lab. Hematol."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1056\/NEJMra2201664","article-title":"Breakthrough Hemolysis in PNH with Proximal or Terminal Complement Inhibition","volume":"387","author":"Notaro","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Gavriilaki, E., Papakonstantinou, A., and Agrios, K.A. (2022). Novel Insights into Factor D Inhibition. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23137216"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3324\/haematol.2016.153312","article-title":"Small-Molecule Factor D Inhibitors Selectively Block the Alternative Pathway of Complement in Paroxysmal Nocturnal Hemoglobinuria and Atypical Hemolytic Uremic Syndrome","volume":"102","author":"Yuan","year":"2017","journal-title":"Haematologica"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.htct.2020.06.006","article-title":"Consensus Statement for Diagnosis and Treatment of Paroxysmal Nocturnal Haemoglobinuria","volume":"43","author":"Sandes","year":"2021","journal-title":"Hematol. Transfus. Cell Ther."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6909a1","article-title":"Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020","volume":"69","author":"Mbaeyi","year":"2020","journal-title":"MMWR. Recomm. Rep."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/s12959-021-00330-6","article-title":"COVID19 Infection in a Patient Undergoing Treatment for Paroxysmal Nocturnal Hemoglobinuria (PNH) with Ravulizumab","volume":"19","author":"Shikdar","year":"2021","journal-title":"Thromb. J."},{"key":"ref_172","first-page":"6619177","article-title":"Severe Hemolysis in a COVID-19 Patient with Paroxysmal Nocturnal Hemoglobinuria","volume":"2021","author":"Otieno","year":"2021","journal-title":"Case Rep. Hematol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1182\/blood-2023-188164","article-title":"Anticoagulation Use and Patient Outcomes in Paroxysmal Nocturnal Hemoglobinuria: A Province-Wide Retrospective Review","volume":"142","author":"Croden","year":"2023","journal-title":"Blood"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1016\/j.molimm.2010.01.021","article-title":"Activation of the Complement System in Normal Pregnancy and Preeclampsia","volume":"47","author":"Derzsy","year":"2010","journal-title":"Mol. Immunol."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s00281-017-0645-x","article-title":"Complement Activation, a Threat to Pregnancy","volume":"40","author":"Girardi","year":"2018","journal-title":"Semin. Immunopathol."},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Venou, T.-M., Vetsiou, E., Varelas, C., Daniilidis, A., Psarras, K., Koravou, E.-E., Koutra, M., Touloumenidou, T., Tsolakidis, V., and Papalexandri, A. (2024). Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia\/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study. J. Pers. Med., 14.","DOI":"10.3390\/jpm14040387"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1056\/NEJMoa1502950","article-title":"Eculizumab in Pregnant Patients with Paroxysmal Nocturnal Hemoglobinuria","volume":"373","author":"Kelly","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1055\/s-0040-1702155","article-title":"Paroxysmal Nocturnal Hemoglobinuria: An Underestimated Cause of Pediatric Thromboembolism","volume":"04","author":"Griesser","year":"2020","journal-title":"TH Open"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1002\/pbc.23410","article-title":"Paroxysmal Nocturnal Hemoglobinuria in Pediatric Patients","volume":"59","author":"Curran","year":"2012","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"2813","DOI":"10.1182\/bloodadvances.2023012267","article-title":"Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of Ravulizumab in Pediatric Paroxysmal Nocturnal Hemoglobinuria","volume":"8","author":"Chonat","year":"2024","journal-title":"Blood Adv."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:30:16Z","timestamp":1760113816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/22\/12104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":180,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["ijms252212104"],"URL":"https:\/\/doi.org\/10.3390\/ijms252212104","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]}}}