{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T13:53:41Z","timestamp":1764510821184,"version":"3.28.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Venous and arterial thromboembolism are major complications of myeloproliferative neoplasms (MPNs), comprising polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Global hemostasis assays, including thrombin generation assay (TGA), rotational thromboelastometry (ROTEM), and thromboelastography (TEG), have been proposed as biomarkers to assess the hypercoagulability and thrombotic risk stratification in MPNs. We performed a systematic literature review on the parameters of TGA, ROTEM, and TEG and their association with thrombotic events and treatment strategies in MPNs. Thirty-two studies (all cross-sectional) were included, which collectively enrolled 1,062 controls and 1,608 MPN patients. Among the 13 studies that reported arterial or venous thrombosis, the overall thrombosis rate was 13.8% with 6 splanchnic thromboses reported. Out of the 27 TGA studies, there was substantial heterogeneity in plasma preparation and trigger reagents employed in laboratory assays. There was a trend toward increased peak height among all MPN cohorts versus controls and higher endogenous thrombin potential (ETP) between ET patients versus controls. There was an overall trend toward lower ETP between PV and PMF patients versus. controls. There were no substantial differences in ETP between JAK2-positive versus JAK2-negative MPNs, prior history versus negative history of thrombotic events, and among different treatment strategies. Of the three ROTEM studies, there was a trend toward higher maximum clot firmness and shorter clot formation times for all MPNs versus controls. The three TEG studies had mixed results. We conclude that the ability of parameters from global hemostasis assays to predict for hypercoagulability events in MPN patients is inconsistent and inconclusive. Further prospective longitudinal studies are needed to validate these biomarker tools so that thrombotic potential could be utilized as a primary endpoint of such studies.<\/jats:p>","DOI":"10.1055\/s-0043-57010","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T23:00:09Z","timestamp":1681772409000},"page":"213-223","source":"Crossref","is-referenced-by-count":2,"title":["The Pitfalls of Global Hemostasis Assays in Myeloproliferative Neoplasms and Future Challenges"],"prefix":"10.1055","volume":"50","author":[{"given":"Andrew","family":"Tiu","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thita","family":"Chiasakul","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, Center of Excellence in Translation Hematology, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig M.","family":"Kessler","sequence":"additional","affiliation":[{"name":"Division of Hematology-Oncology, Lombardi Comprehensive Cancer Center, MedStar Georgetown University Hospital, Washington, District of Columbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"issue":"22","key":"ref1","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1056\/NEJMra1406186","article-title":"Myeloproliferative neoplasms","volume":"376","author":"J L Spivak","year":"2017","journal-title":"N Engl J Med"},{"issue":"01","key":"ref2","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s12885-019-5387-9","article-title":"A systematic review and meta-analysis of the prevalence of thrombosis and bleeding at diagnosis of Philadelphia-negative myeloproliferative neoplasms","volume":"19","author":"T Rungjirajittranon","year":"2019","journal-title":"BMC Cancer"},{"issue":"05","key":"ref3","doi-asserted-by":"crossref","first-page":"317","DOI":"10.7326\/M17-0028","article-title":"Risk for arterial and venous thrombosis in patients with myeloproliferative neoplasms: a population-based cohort study","volume":"168","author":"M Hultcrantz","year":"2018","journal-title":"Ann Intern Med"},{"issue":"10","key":"ref4","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1200\/JCO.2005.07.062","article-title":"Vascular and neoplastic risk in a large cohort of patients with polycythemia vera","volume":"23","author":"R Marchioli","year":"2005","journal-title":"J Clin Oncol"},{"issue":"26","key":"ref5","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1182\/blood-2012-07-444067","article-title":"Development and validation of an international prognostic score of thrombosis in World Health Organization-essential thrombocythemia (IPSET-thrombosis)","volume":"120","author":"T Barbui","year":"2012","journal-title":"Blood"},{"issue":"17","key":"ref6","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1200\/JCO.2018.78.9867","article-title":"MIPSS70+ version 2.0: mutation and karyotype-enhanced international prognostic scoring system for primary myelofibrosis","volume":"36","author":"A Tefferi","year":"2018","journal-title":"J Clin Oncol"},{"issue":"08","key":"ref7","doi-asserted-by":"crossref","first-page":"e605","DOI":"10.1016\/S2352-3026(21)00171-X","article-title":"Improving the investigative approach to polycythaemia vera: a critical assessment of current evidence and vision for the future","volume":"8","author":"L Ronner","year":"2021","journal-title":"Lancet Haematol"},{"issue":"12","key":"ref8","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1007\/s00277-013-1834-x","article-title":"Global coagulation in myeloproliferative neoplasms","volume":"92","author":"A Tripodi","year":"2013","journal-title":"Ann Hematol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.thromres.2019.04.033","article-title":"A review of global coagulation assays - Is there a role in thrombosis risk prediction?","volume":"179","author":"H Y Lim","year":"2019","journal-title":"Thromb Res"},{"issue":"01","key":"ref10","first-page":"1","article-title":"Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?","volume":"7","author":"L L Ma","year":"2020","journal-title":"Mil Med Res"},{"issue":"S 01","key":"ref11","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1097\/01.HS9.0000567404.64167.17","article-title":"The natural anticoagulants in patients with Philadelphia-negative myeloproliferative neoplasms","volume":"3","author":"E Efremova","year":"2019","journal-title":"HemaSphere"},{"issue":"S 01","key":"ref12","first-page":"173","article-title":"Microparticle-associated thrombin generation in patients with philadelphia-negative myeloproliferative neoplasms","volume":"4","author":"O Matvienko","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"S 01","key":"ref13","first-page":"1051","article-title":"Increased coagulation potential in patients with polycythemia vera and essential thrombocythemia with thrombotic history","volume":"4","author":"N Korsakova","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"03","key":"ref14","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.thromres.2010.06.025","article-title":"Increased circulating procoagulant activity and thrombin generation in patients with myeloproliferative neoplasms","volume":"126","author":"J Duchemin","year":"2010","journal-title":"Thromb Res"},{"issue":"S 01","key":"ref15","first-page":"79","article-title":"Evaluation of thromboelastography (TEG) in patients with myeloproliferative neoplasm (MPN): platelet count > 600 associated with prothrombotic parameters","volume":"14","author":"C Ng","year":"2016","journal-title":"J Thromb Haemost"},{"issue":"09","key":"ref16","first-page":"1373","article-title":"Thrombin generation testing in patients with myelofibrosis","volume":"64","author":"M Palova","year":"2018","journal-title":"Clin Lab"},{"issue":"07","key":"ref17","doi-asserted-by":"crossref","first-page":"911","DOI":"10.3324\/haematol.13774","article-title":"Elevated procoagulant microparticles expressing endothelial and platelet markers in essential thrombocythemia","volume":"94","author":"M C Trappenburg","year":"2009","journal-title":"Haematologica"},{"issue":"03","key":"ref18","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1097\/MBC.0000000000000724","article-title":"An evaluation of global coagulation assays in myeloproliferative neoplasm","volume":"29","author":"H Y Lim","year":"2018","journal-title":"Blood Coagul Fibrinolysis"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1182\/blood-2008-06-164087","article-title":"Thrombin generation and activated protein C resistance in patients with essential thrombocythemia and polycythemia vera","volume":"112","author":"M Marchetti","year":"2008","journal-title":"Blood"},{"issue":"06","key":"ref20","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3109\/09537104.2011.633178","article-title":"Evaluation of hemostatic balance in blood from patients with polycythemia vera by means of thromboelastography: the effect of isovolemic erythrocytapheresis","volume":"23","author":"T Rusak","year":"2012","journal-title":"Platelets"},{"issue":"12","key":"ref21","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1002\/ajh.23553","article-title":"Thrombin generation and procoagulant phospholipids in patients with essential thrombocythemia and reactive thrombocytosis","volume":"88","author":"I Mignon","year":"2013","journal-title":"Am J Hematol"},{"issue":"S 01","key":"ref22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-99-118487","article-title":"Platelet-dependent thrombin generation induced by ADP or activated factor X does not contribute to increased in vivo thrombin formation in myeloproliferative neoplasms","volume":"132","author":"C Berens","year":"2018","journal-title":"Blood"},{"issue":"03","key":"ref23","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.bcmd.2011.01.003","article-title":"Polymorphonuclear neutrophils from JAK2(V617F) positive MPD patients do not support hypercoagulability: a study with calibrated automated thrombography (CAT)","volume":"46","author":"J Perrin","year":"2011","journal-title":"Blood Cells Mol Dis"},{"issue":"S 02","key":"ref24","first-page":"600","article-title":"Endogenous thrombin potential (ETP) in myeloproliferative disorders (MPD)","volume":"95","author":"E Papakonstantinou","year":"2010","journal-title":"Haematologica"},{"issue":"21","key":"ref25","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1182\/blood.V120.21.1145.1145","article-title":"Tissue-factor bearing microparticles and thrombotic risk in the myeloproliferative neoplasms","volume":"120","author":"B L Stein","year":"2012","journal-title":"Blood"},{"issue":"01","key":"ref26","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1002\/ajh.23590","article-title":"Phospholipid-dependent procoagulant activity is highly expressed by circulating microparticles in patients with essential thrombocythemia","volume":"89","author":"M Marchetti","year":"2014","journal-title":"Am J Hematol"},{"key":"ref27","first-page":"86","article-title":"Increased numbers of microparticles and microparticle specific thrombin generation in patients with myeloproliferative disease","volume":"28","author":"M C Van Aalderen","year":"2010","journal-title":"Clin Exp Rheumatol"},{"key":"ref28","first-page":"49","article-title":"Monocyte (MNC) hemostatic profile in essential thrombocythemia (ET) or polycythemia vera (PV) patients is influenced by JAK2V617F mutational load","volume":"7","author":"A Vignoli","year":"2009","journal-title":"J Thromb Haemost"},{"issue":"01","key":"ref29","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.thromres.2013.05.003","article-title":"ADP-induced platelet aggregation and thrombin generation are increased in essential thrombocythemia and polycythemia vera","volume":"132","author":"M Panova-Noeva","year":"2013","journal-title":"Thromb Res"},{"issue":"S 01","key":"ref30","first-page":"97","article-title":"Efficiency of anticoagulant protein c system in patients with primary myelofibrosis","volume":"3","author":"O Matvienko","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"issue":"S 02","key":"ref31","first-page":"703","article-title":"The coagulation system functioning in patients with myelofibrosis","volume":"2","author":"E Efremova","year":"2018","journal-title":"HemaSphere"},{"issue":"05","key":"ref32","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1111\/ijlh.12676","article-title":"The evaluation of the relevance of thrombin generation and procoagulant activity in thrombotic risk assessment in BCR-ABL-negative myeloproliferative neoplasm patients","volume":"39","author":"H Baccouche","year":"2017","journal-title":"Int J Lab Hematol"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1002\/ajh.21974","article-title":"Platelet-induced thrombin generation by the calibrated automated thrombogram assay is increased in patients with essential thrombocythemia and polycythemia vera","volume":"86","author":"M Panova-Noeva","year":"2011","journal-title":"Am J Hematol"},{"issue":"04","key":"ref34","doi-asserted-by":"crossref","first-page":"992","DOI":"10.3390\/cancers12040992","article-title":"Interferon alpha therapy increases pro-thrombotic biomarkers in patients with myeloproliferative neoplasms","volume":"12","author":"D Faille","year":"2020","journal-title":"Cancers (Basel)"},{"issue":"S 02","key":"ref35","first-page":"433","article-title":"Hydroxyurea reduces thrombin generation (TG)","volume":"9","author":"C Caron","year":"2011","journal-title":"J Thromb Haemost"},{"issue":"S 01","key":"ref36","first-page":"175","article-title":"Influence of specific therapy on microparticle-associated thrombin generation in patients with primary myelofibrosis","volume":"4","author":"O Matvienko","year":"2020","journal-title":"Res Pract Thromb Haemost"},{"issue":"S 02","key":"ref37","first-page":"830","article-title":"Effect of therapy on thrombin generation in patients with polycythemia vera","volume":"5","author":"N Silina","year":"2021","journal-title":"Res Pract Thromb Haemost"},{"issue":"S 05","key":"ref38","first-page":"s792","article-title":"Rotational thrombo elastometry (ROTEM) detects the hypercoagulable profile of patients with essential thrombocythemia (ET) and polycythemia vera (PV) and is influenced by mutational status","volume":"14","author":"C Giaccherini","year":"2016","journal-title":"Blood Transfus"},{"issue":"02","key":"ref39","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1080\/09537104.2020.1742309","article-title":"Use of rotational thromboelastometry for a global screening of coagulation profile in patients of myeloproliferative neoplasms","volume":"32","author":"D G \u015eahin","year":"2021","journal-title":"Platelets"},{"issue":"08","key":"ref40","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1111\/jth.14863","article-title":"Towards standardization of thrombin generation assays: inventory of thrombin generation methods based on results of an International Society of Thrombosis and Haemostasis Scientific Standardization Committee survey","volume":"18","author":"R MW de Laat-Kremers","year":"2020","journal-title":"J Thromb Haemost"},{"issue":"05","key":"ref41","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.1111\/jth.15287","article-title":"Recommendations for the measurement of thrombin generation: communication from the ISTH SSC Subcommittee on Lupus Anticoagulant\/Antiphospholipid Antibodies","volume":"19","author":"M Ninivaggi","year":"2021","journal-title":"J Thromb Haemost"},{"issue":"12","key":"ref42","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/s41408-021-00581-6","article-title":"JAK2V617F variant allele frequency >50% identifies patients with polycythemia vera at high risk for venous thrombosis","volume":"11","author":"P Guglielmelli","year":"2021","journal-title":"Blood Cancer J"},{"issue":"09","key":"ref43","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1182\/blood.2020008043","article-title":"Clinical insights into the origins of thrombosis in myeloproliferative neoplasms","volume":"137","author":"A R Moliterno","year":"2021","journal-title":"Blood"},{"issue":"S 01","key":"ref44","first-page":"266","article-title":"The coagulation system state in patients with Philadelphia-negative myeloproliferative neoplasms","volume":"2","author":"N Silina","year":"2018","journal-title":"Res Pract Thromb Haemost"},{"issue":"S 01","key":"ref45","first-page":"573","article-title":"Determinants of clot strength in polycythemia vera and primary myelofibrosis using rotational thromboelastometry","volume":"1","author":"N Nytofte","year":"2017","journal-title":"Res Pract Thromb Haemost"}],"container-title":["Seminars in Thrombosis and Hemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-57010.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T11:45:57Z","timestamp":1730807157000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-57010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,17]]},"references-count":45,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2024,2,5]]},"published-print":{"date-parts":[[2024,3]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-57010","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0094-6176","1098-9064"],"issn-type":[{"type":"print","value":"0094-6176"},{"type":"electronic","value":"1098-9064"}],"subject":[],"published":{"date-parts":[[2023,4,17]]}}}