{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T16:21:54Z","timestamp":1792167714400,"version":"4.4.0"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Disseminated intravascular coagulation (DIC) is a serious complication of acute myeloid leukemia (AML) associated with poor prognosis. In TP53-mutated AML and myelodysplastic syndrome (MDS), however, the classical ISTH criteria rarely identify overt DIC, although bleeding and thrombotic complications are well documented in acute leukaemia. We hypothesized that these patients exhibit a lower-grade, subclinical coagulation activation that is associated with the underlying genomic-instability-related features of TP53-mutant disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 107 consecutive patients with TP53-mutated AML (n = 52) or high-risk MDS (MDS, n = 55), median age 65 years, diagnosed and initially evaluated at our centre between 2018 and 2025. Seven routine coagulation markers and 46 co-mutated genes were evaluated for associations with overall survival (OS) using univariate and multivariable Cox regression, continuous dose\u2013response modeling, and unsupervised k-means clustering. Internal validity was assessed by 1000 bootstrap resamples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Overt DIC according to ISTH criteria was rare (15%). Subclinical activation was common: 50% of patients had a D-dimer \u22651\u00a0\u03bcg\/mL, 41% a fibrinogen \u22654\u00a0g\/L, and 29% an INR \u22651.2. In univariate analysis, D-dimer, fibrinogen, INR, prothrombin time, and activated partial thromboplastin time were each associated with OS (HR 1.33\u20131.38 per SD; all p &amp;lt; 0.05). Complex karyotype correlated with higher D-dimer (median 1.39 vs. 0.60\u00a0\u03bcg\/mL, p = 0.022) and fibrinogen (3.91 vs. 2.53\u00a0g\/L, p = 0.007), while TP53 variant allele frequency (VAF) showed modest positive correlations with D-dimer (\u03c1 = 0.21), INR (\u03c1 = 0.27), and PT (\u03c1 = 0.27; all p &amp;lt; 0.05). Clustering identified three coagulation phenotypes: Silent (51%), Thrombo-inflammatory (31%), and Consumption-like (18%), showing a graded but statistically non-significant gradient in molecular features and a stepwise decline in median OS (14, 10 and 8 months; log-rank p = 0.041). After adjustment for complex karyotype, TP53 VAF, and favorable co-mutation count, the Consumption-like phenotype was associated with a non-significant increased risk (HR 1.83, 95% CI 0.92\u20133.65, p = 0.084), whereas favorable co-mutation pathways remained independently protective (HR 0.56, 95% CI 0.35\u20130.90, p = 0.016).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In TP53-mutated AML\/MDS, coagulation activation intensity is associated with the degree of genomic instability. The three phenotypes may add biological resolution beyond classical DIC and cytogenetic risk groups, but represent laboratory patterns rather than validated bleeding or thrombosis prediction tools. However, after accounting for genomic features, phenotypes were not independent predictors of outcome, with complex karyotype, TP53 VAF, and favorable co-mutation count driving prognosis. Because treatment intensity and other clinical confounders were not available, these survival associations are hypothesis-generating. Coagulation profiling remains inexpensive, widely accessible, and offers a practical window into disease biology that warrants prospective validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1918027","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:35Z","timestamp":1787290655000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Coagulation activation is associated with genomic-instability-related features in TP53-mutated AML and MDS: routine laboratory patterns beyond classical disseminated intravascular coagulation"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiaoqin","family":"Xin","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Ganzhou People\u2019s Hospital","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaoqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Ganzhou People\u2019s Hospital","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ganzhou Maternal and Child Health Hospital","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ganzhou Maternal and Child Health Hospital","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1038\/s41591-020-1008-z","article-title":"Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes","volume":"26","author":"Bernard","year":"2020","journal-title":"Nat. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1617","DOI":"10.1182\/blood.2023023727","article-title":"Molecular taxonomy of myelodysplastic syndromes and its clinical implications","volume":"144","author":"Bernard","year":"2024","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1158\/2159-8290.CD-22-0332","article-title":"TP53-Mutated myelodysplastic syndrome and acute Myeloid leukemia: biology, current therapy, and future directions","volume":"12","author":"Daver","year":"2022","journal-title":"Cancer Discov."},{"key":"B4","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1016\/j.ccell.2024.04.004","article-title":"Putting the STING back into BH3-mimetic drugs for TP53-mutant blood cancers","volume":"42","author":"Diepstraten","year":"2024","journal-title":"Cancer Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"4597","DOI":"10.1007\/s10238-023-01241-8","article-title":"Albumin-to-fibrinogen ratio is an independent prognostic parameter in de novo non-M3 acute myeloid leukemia","volume":"23","author":"Ding","year":"2023","journal-title":"Clin. Exp. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1111\/jth.12075","article-title":"Coagulation and cancer: biological and clinical aspects","volume":"11","author":"Falanga","year":"2013","journal-title":"J. Thrombosis Haemostasis Jth"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1182\/blood-2013-04-460139","article-title":"Tumor-derived tissue factor-positive microparticles and venous thrombosis in cancer patients","volume":"122","author":"Geddings","year":"2013","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1182\/blood.2021014472","article-title":"Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome","volume":"139","author":"Grob","year":"2022","journal-title":"Blood"},{"key":"B9","doi-asserted-by":"publisher","first-page":"102393","DOI":"10.1016\/j.bcmd.2019.102393","article-title":"Coagulopathy in cytogenetically and molecularly distinct acute leukemias at diagnosis: comprehensive study","volume":"81","author":"Guo","year":"2020","journal-title":"Blood Cells, Mol. and Dis."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S58","DOI":"10.1016\/S0049-3848(20)30398-4","article-title":"Thrombosis in hematological malignancies: mechanisms and implications","volume":"191","author":"Horowitz","year":"2020","journal-title":"Thromb. Res."},{"key":"B11","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1161\/ATVBAHA.110.215061","article-title":"p53 impairs endothelial function by transcriptionally repressing kruppel-like factor 2","volume":"31","author":"Kumar","year":"2011","journal-title":"Arteriosclerosis, Thrombosis, Vasc. Biol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1854","DOI":"10.1182\/blood-2016-02-701094","article-title":"Disseminated intravascular coagulation at diagnosis is a strong predictor for thrombosis in acute myeloid leukemia","volume":"128","author":"Libourel","year":"2016","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1182\/blood-2015-03-633537","article-title":"SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts","volume":"126","author":"Malcovati","year":"2015","journal-title":"Blood"},{"key":"B14","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.3390\/diagnostics15233053","article-title":"Predicting bleeding in AML-Associated DIC: limitations of the ISTH Score and a modified approach","volume":"15","author":"Orhan","year":"2025","journal-title":"Diagn. (Basel)"},{"key":"B15","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1186\/s12959-023-00506-2","article-title":"Simplified predictive scores for thrombosis and bleeding complications in newly diagnosed acute leukemia patients","volume":"21","author":"Owattanapanich","year":"2023","journal-title":"Thromb. J."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2209","DOI":"10.1056\/NEJMoa1516192","article-title":"Genomic classification and prognosis in Acute Myeloid leukemia","volume":"374","author":"Papaemmanuil","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"e976","DOI":"10.1016\/j.clml.2025.07.013","article-title":"Curing the incurable: TP53 mutated Myeloid neoplasms","volume":"25","author":"Punwani","year":"2025","journal-title":"Clin. Lymphoma, Myeloma and Leukemia"},{"key":"B18","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/978-0-387-79962-9_3","article-title":"Activation of clotting factors in cancer","volume":"148","author":"Rickles","year":"2009","journal-title":"Cancer Treat. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1182\/blood-2011-08-375758","article-title":"TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome","volume":"119","author":"R\u00fccker","year":"2012","journal-title":"Blood"},{"key":"B20","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1038\/s41408-025-01290-0","article-title":"Validation of the","volume":"15","author":"Shah","year":"2025","journal-title":"Blood Cancer J."},{"key":"B21","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3390\/diagnostics15030383","article-title":"Hematopathological patterns in Acute Myeloid leukemia with complications of overt disseminated intravascular coagulation","volume":"15","author":"Strasser","year":"2025","journal-title":"Diagnostics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1182\/blood.2021013983","article-title":"TP53 copy number and protein expression inform mutation status across risk categories in acute myeloid leukemia","volume":"140","author":"Tashakori","year":"2022","journal-title":"Blood"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1055\/s-0037-1616068","article-title":"Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation","volume":"86","author":"Taylor","year":"2001","journal-title":"Thromb. Haemost."},{"key":"B24","doi-asserted-by":"publisher","first-page":"4622","DOI":"10.1038\/s41467-022-32103-8","article-title":"Unified classification and risk-stratification in Acute Myeloid Leukemia","volume":"13","author":"Tazi","year":"2022","journal-title":"Nat. Commun."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1056\/NEJMoa1605949","article-title":"TP53 and decitabine in Acute Myeloid leukemia and myelodysplastic syndromes","volume":"375","author":"Welch","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.yjmcc.2019.02.010","article-title":"p53 plays a crucial role in endothelial dysfunction associated with hyperglycemia and ischemia","volume":"129","author":"Yokoyama","year":"2019","journal-title":"J. Mol. Cell Cardiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"12484","DOI":"10.1038\/ncomms12484","article-title":"Clonal haematopoiesis harbouring AML-associated mutations is ubiquitous in healthy adults","volume":"7","author":"Young","year":"2016","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1918027\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T05:37:36Z","timestamp":1787290656000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2026.1918027\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":27,"alternative-id":["10.3389\/fcell.2026.1918027"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2026.1918027","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"article-number":"1918027"}}