title: Microparticle-associated tissue factor activity in patients with metastatic pancreatic cancer and its effect on fibrin clot formation.
abstract: Highly elevated microparticle (MP)-associated tissue factor (TF) activity was found in patients with pancreatic cancer, one of the most prothrombotic malignancies. It remains to be elucidated whether MP-TF activity reflects the prothrombotic state in these patients. MP-TF activity levels and the TF-dependent and -independent effect of MPs on fibrin clot formation were determined in patients with metastatic pancreatic cancer (n = 27), in healthy individuals (n = 10) and in plasma samples from lipopolysaccharide (LPS)-stimulated blood (LPS-plasma), which is rich in monocyte-derived TF-bearing MPs. The median MP-TF activity was 1.06 pg/mL (range, from 0.19 to 10.34 pg/mL) in patients with pancreatic cancer, 0.61 pg/mL (range, from 0.36 to 0.79 pg/mL) in LPS-plasma, and 0.18 pg/mL (range, from 0.04 to 0.39 pg/mL) in healthy individuals. MPs derived from LPS-plasma had the strongest impact on fibrin clot formation time (median, 157.6 seconds; range, from 149.5 to 170.4 seconds). Fibrin clot formation occurred significantly later in MPs derived from patients with pancreatic cancer (median, 273.4 seconds; range, from 146.6 to 354.4 seconds; P < 0.001) and in healthy individuals (median, 299.0 seconds; range, from 261.1 to 417.9 seconds; P < 0.001). Only in MPs derived from LPS-plasma the fibrin clot formation time dependent strongly on TF (median prolongation after TF blockade: 68% in LPS-plasma, 10% in patients with pancreatic cancer, and 4% in healthy individuals). In conclusion, highly elevated MP-TF activity was found in patients with metastatic pancreatic cancer, but TF-bearing MPs had a small effect on fibrin clot formation. TF-bearing MPs might not be the main mediators of the prothrombotic state associated with pancreatic cancer. However, the small but significant increase in coagulation potential by TF-bearing MPs might contribute to the multifactorial pathogenesis of venous thromboembolism in pancreatic cancer.
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Vienna, Austria; Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Johannes
authors: J
authors: Thaler
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Vienna, Austria; Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Silvia
authors: S
authors: Koder
authors: Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Austria.
authors: Gabriela
authors: G
authors: Kornek
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Vienna, Austria; Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors: Ingrid
authors: I
authors: Pabinger
authors: Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Vienna, Austria; Comprehensive Cancer Center Vienna, Medical University of Vienna, Vienna General Hospital, Vienna, Austria. Electronic address: cihan.ay@meduniwien.ac.at.
authors: Cihan
authors: C
authors: Ay
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005337:Fibrin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism
chemical_list: D005337:Fibrin; D013925:Thromboplastin