Identifying Novel Coagulation Biomarkers for Thrombosis in Patients with Lymphoma

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.4023-4023
• Main Authors: Antic, Darko, Otasevic, Vladimir, Mitrovic-Ajtic, Olivera, Djikic, Dragoslava, Zivkovic, Emilija, Dragojevic, Teodora, Ivanovic, Jelena, Stanisavljevic, Dejana, Milic, Natasa, Vukotic, Milica, Suboticki, Tijana, Diklic, Milos, Santibanez, Juan F., Vukovic, Vojin, Kozarac, Sofija, Pesic, Andrej, Mihaljevic, Biljana, Fareed, Jawed, Cokic, Vladan P.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-185006

Thromboembolic events are a common complication of lymphoma, influenced by a number of factors, including status of the disease, patient characteristics and treatment modalities. Recent studies demonstrated presence of hemostatic dysregulation in lymphoma patients with the possible involvement of tissue factor (TF) in the development of thrombotic events; however, more data are needed to link coagulation biomarkers' levels with clinical data and increased thrombotic risk. TF initiates blood coagulation and expressed by nonvascular cells plays a major role in hemostasis, while TF expressed by vascular cells induces intravascular thrombosis. In this study, we aimed to profile coagulation biomarkers and determine the roles of neutrophils, monocytes, platelets and endothelial cells and their interactions in thrombus formation in patients with lymphoma. Patients with newly diagnosed lymphoma were prospectively recruited and followed for all thromboembolic events from the time of diagnosis until 3 months after the last cycle of therapy. Peripheral blood samples were obtained before hematological treatment initiation from 127 patients with lymphoma. The coagulation factors profile (Fibrinogen, P-selectin, FVIII, Thrombin and TF) was measured by enzyme-linked immunosorbent assay (ELISA), while TF expression and monocyte-platelet aggregates were determined by flow cytometry. The isolation, quantification and flow cytometry profiling of extracellular vesicles (EVs) ≤1.0 µm have been done according to the protocol developed by Institute for Medical Research, Belgrade, Serbia. Thromboembolic events were diagnosed objectively based on clinical examination, radiographic studies and laboratory evaluation. The mean patients' age was 55±16 years (range, 18-86 years); 44.9% were males. Most patients (58.2%) had advanced stage disease (III/IV), and 35.4% had ECOG performance status ≥1. More than half of the patients had aggressive forms of lymphoma (64.6%), mostly diffuse large B-cell lymphoma (DLBCL). Thrombosis occurred in 14.3% of patients with lymphoma (18/127), predominantly in patients with aggressive (18.3%) vs. indolent forms (6.8%). Total number of thrombosis was 22 (4 patients had more than one thrombosis site), and venous thrombosis was the most prevalent (72.7%). ThroLy score ≥2 had 72.2% of patients with thrombosis, in contrast to 37% of patients without thrombosis. The median value of TF was higher in patients with thrombosis compared to those without thrombosi