Measurement of tissue factor messenger RNA levels in leukocytes from patients with underlying diseases of disseminated intravascular coagulation

Abstract number: P0901

Sase T., Wada H., Nishioka J., Abe Y., Nobori T., Shiku H.

Mie University School of Medicine, Japan

Introduction  

Tissue factor (TF) is known as the major initiator of the coagulation system activation, triggering the thrombotic response in a variety of diseases, including sepsis and leukemia. It was recently suggested that TF present in the circulating blood may participate in both hemostasis and thrombosis. The source of circulating TF antigen is not known but it is presumably derived from cells expressing TF by shedding. However, most TF protein with high activity exists on the surface of cells, and cannot be measured as soluble form by enzyme immunoassay. We measured TF mRNA in leukocytes in various diseases and examined its relationship with the pathophysiology of various diseases.

Materials and methods  

The levels of mRNA in leukocytes were measured in eight patients with thrombotic diseases, nine with autoimmune diseases, 36 with solid cancer, 34 with hematopoietic tumor, 26 with infectious diseases and 20 with other diseases. RNA was extracted from whole blood and Real-Time quantitative polymerase chain reaction (PCR) was performed using the TaqMan PCR kit. TF antigen was measured by one-step sandwich enzyme-linked immuno-sorbent assay using a commercial kit.

Results  

TF mRNA in leukocytes were low in healthy volunteer but they were significantly increased in various diseases, especially in patients with infectious diseases, solid cancer, and hematopoietic tumors. The TF mRNA/GAPDH mRNA ratio in leukocytes were significantly higher in patients with high C reactive protein (CRP) than in those with low CRP (P < 0.05). TF mRNA/GAPDH mRNA ratio was significantly higher in patients with disseminated intravascular coagulation (DIC) than in those without DIC (P < 0.001). TF mRNA/GAPDH mRNA ratio was well correlated with TF antigens in plasma(r = 0.384, P = 0.053) and leukocytes (r = 0.772, P < 0.001).

Discussion  

These findings suggest that the expression of TF mRNA in leukocytes may play an important role in hypercoagulability or DIC and that measurement of TF mRNA in leukocytes may be more useful for the diagnosis of DIC than measurement of plasma TF antigen.