Journal
THROMBOSIS RESEARCH
Volume 199, Issue -, Pages 21-31Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2020.12.018
Keywords
CA 19-9 antigen; Extracellular vesicles; Pancreatic neoplasms; Thrombin; Tissue factor
Categories
Funding
- Finnish Governmental Funding (VTR)
- Heart Research Foundation
- Sigrid Juselius Foundation
- Cancer Foundation Finland
- Japanese Society on Thrombosis and Hemostasis
- National Institutes of Health [T32 HL007149, R01 HL147149]
- Inkeri and Mauri Vanska Foundation
- John C. Parker Professorship
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This study examined the association between CA 19-9 and thrombin generation in plasma from PDAC patients, finding that CA 19-9 levels were linked to several TG parameters. Additionally, some commercial sources of CA 19-9 were shown to enhance TG in SHP in patients prior to any pancreatic cancer treatments or signs of VTE.
Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a hypercoagulable state and high mortality. Increases in the plasma levels of tumor marker carbohydrate antigen (CA) 19-9 are used in diagnosis and follow-up but have also been reported to precede venous thromboembolism (VTE). Aims: We examined the association between CA 19-9 and thrombin generation (TG) in plasma from PDAC patients, as well as their association with coagulation biomarkers prior to pancreatic surgery. In addition, we determined the effect of commercial sources of CA 19-9 on TG. Methods: We collected plasma from 58 treatment-naive PDAC patients without any signs of VTE. We measured levels of CA 19-9, FVIII, fibrinogen, D-dimer, antithrombin and extracellular vesicle (EV) tissue factor (TF) activity and TG using a Calibrated Automated Thrombogram (CAT). The effect of different commercial sources of CA 19-9 on TG in Standard Human Plasma (SHP) was also studied. Results: Patient plasma samples were divided into 4 preoperative groups based on the level of CA 19-9: none < 2, low = 3200, high = 201-1000, and very high > 1000 U/mL. CA 19-9 levels were associated with several of the TG parameters, including endogenous thrombin potential, peak, and time to peak. CA 19-9 did not associate with any of the coagulation biomarkers. Spiking of SHP with CA 19-9 increased TG but this was decreased by an antiTF antibody. Conclusions: CA 19-9 was associated with TG in patients prior to any pancreatic cancer treatments or signs of VTE. Some commercial sources of CA 19-9 enhanced TG in SHP seemingly due to contaminating TF.
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