Plasma Clot Properties in Patients with Pancreatic Cancer

We detected an increased plasma clot formation rate and an increased delta absorbance (DAbs, indicating fibrin fiber thickness) in pancreatic cancer patients compared to sexmatched healthy controls applying a modified plasma clot formation assay, in which only CaCl2 and phospholipids were added to initiate clotting. Following addition of a tissue factor blocking antibody in our modified assay, the plasma clot formation rate decreased significantly in patients only, DAbs significantly decreased in patients and in healthy controls, the lag phase did not change, and the time to peak fibrin generation increased in patients only. Taken together, these findings indicate the presence of a prothrombotic state in pancreatic cancer patients, which depends on tissue factor. Pancreatic cancer is one of the most prothrombotic malignancies. Plasma clot properties may be altered in patients with pancreatic cancer, and circulating tissue factor (TF) may play an important role. We applied a modified plasma clot formation assay (only CaCl2 and phospholipids were added to initiate clotting) and a standard clotting assay (lipidated TF was also added) to investigate whether plasma clot properties are altered in pancreatic cancer patients (n = 40, 23 female) compared to sex-matched healthy controls. The modified assay was also performed in the presence of a TF blocking antibody. With this modified assay, we detected an increased plasma clot formation rate (Vmax) and an increased delta absorbance (Delta Abs, indicating fibrin fiber thickness) in patients compared to controls. These differences were not detected with the standard clotting assay. Following addition of a TF blocking antibody in in our modified assay, Vmax decreased significantly in patients only, Delta Abs significantly decreased in patients and in healthy controls, the lag phase did not change, and the time to peak fibrin generation increased in patients only. Taken together, these findings indicate the presence of a prothrombotic state in pancreatic cancer patients, which depends on TF and is detectable with our modified assay but not with a standard clotting assay.

Automated summary

Using a modified plasma clot formation assay, we found an increased plasma clot formation rate and fibrin fiber thickness in pancreatic cancer patients compared to healthy controls. When a tissue factor blocking antibody was added, the clot formation rate decreased significantly in patients, fibrin fiber thickness decreased in patients and controls, the lag phase remained unchanged, and the time to peak fibrin generation increased in patients. These findings suggest the presence of a prothrombotic state in pancreatic cancer patients, dependent on tissue factor.