CO010 | MAPPING HEMOSTATIC BIOMARKER EXPRESSION ACROSS CANCER TYPES AND STAGES WITHIN THE HYPERCAN COHORT

P. Gómez-Rosas^1|2, D. Romeo¹, S. Bolognini¹, C. Ticozzi¹, F. Schieppati^1|4|5, A. D’Alessio³, R. Labianca³, L. Barcella^1|4|5, A. Falanga^3|5, M. Marchetti^1|4|5 | ¹Hospital Papa Giovanni XXIII, Bergamo, Italy; ²Hospital de Oncología, Unidad Médica de Alta Especialidad (UMAE), Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de México, México; ³Fondazione ARTET Onlus, Bergamo, Italy; ⁴ERN EuroBloodNet; ⁵School of Medicine and Surgery, University of Milan Bicocca, Italy. On behalf of the HYPERCAN Investigators

Background and Aims. Systemic hypercoagulability is a recognized hallmark of malignancy. Growing evidence suggests that markers of hemostatic activation may serve as surrogates for tumor aggressiveness and prognosis, other than thrombosis; however, a comprehensive characterization of this "hemostatic signature" within an inflammatory milieu across large prospective cohorts remains limited. This study aims to evaluate tumor-specific procoagulant profiles within a large, prospective, multicenter cohort of patients diagnosed with common solid malignancies.
Methods. We analyzed 4,292 patients from the HYPERCAN study (NCT02622815) with newly diagnosed non-small cell lung (NSCLC), gastric (GC), colorectal (CRC), and breast cancer (BC). Plasma samples were collected at diagnosis to assess thrombin generation (TG_CAT), D-dimer, fibrinogen, and prothrombin fragment 1+2 (F1+2). All participants provided informed consent, and data were analyzed using SPSS 21.0.
Results. Metastatic disease was predominant in the NSCLC (67%), GC (53%), and CRC (47%) cohorts, whereas 75% of the BC cohort consisted of high-risk surgically resected patients. Fibrinogen levels were significantly elevated in metastatic cases compared with resected cases across all tumor types (p < 0.001), with the highest concentrations observed in metastatic NSCLC. Notably, CRC exhibited a stage-dependent, stepwise increase in fibrinogen (348 to 444 mg/dL; p < 0.05). While FVIII was consistently higher in metastatic groups (except GC), D-dimer peaks were most pronounced in metastatic GC and NSCLC (p < 0.002). Although F1+2 effectively differentiated metastatic from localized disease in NSCLC, GC, and BC (p < 0.05), it showed no discriminatory power in CRC. Finally, the highest TG-Peak and ETP values were found in BC and NSCLC; in the latter, TG values positively correlated with disease burden, significantly distinguishing metastatic from resected patients (p < 0.003).
Conclusions. These data demonstrate that cancer-associated hypercoagulability is a heterogeneous, tumor-specific hallmark rather than a uniform systemic event. While fibrinogen and D-dimer remain robust indicators of metastatic progression—particularly in NSCLC and GC—the sensitivity of markers like F1+2 and TG varies by histotype. These findings underscore the necessity of tailored hemostatic profiling to better understand biological heterogeneity and improve risk stratification across diverse malignancies.