Phospholipid-dependent clotting time is able to identify cancer patients with high levels of circulating microparticles

Introduction: Circulating procoagulant microparticles (MP) have been associated with a prothrombotic state in many diseases, including cancer. MP can enhance thrombin formation by exposing tissue factor (TF), the initiator of coagulation in vivo. Whether procoagulant TF is really exposed on circulating MP in cancer, however, is still debated. In addition, MP can also expose procoagulant phospholipids, which are essential for propagation of coagulation. In this study, we determined the contribution of circulating MP to phospholipid (PPL)-dependent coagulation in plasma samples from a heterogeneous group of cancer patients and compared them to healthy subjects. Methods: Citrate-anticoagulated blood was collected from healthy subjects (n = 85) and cancer patients (n = 50). The procoagulant activity of circulating MP was measured in fresh plasma using the STA procoag PPL assay (Diagnostica Stago). Results: The mean age of healthy subjects was 54 ± 12 years and 62% was female. The PPL-dependent clotting time (CTPPL) was 77.8 s ± 8.7 (mean ± SD, normal distribution), gender independent (P = 0.97) and not associated with age (r = 0.24, P = 0.83). Both removal of MP by high speed centrifugation or addition of annexin V strongly prolonged the CTPPL, indicating that MP are indeed the main source of PPL under these conditions. With regard to plasma samples from cancer patients, seven patients (14%) showed a faster CTPPL than controls (below 2.5 percentile). Five of these patients had metastatic disease (four gastrointestinal, one pancreatic cancer). The other two had local disease (one breast and one gastrointestinal cancer). Conclusions: The CTPPL is useful in identifying cancer patients with high levels of circulating procoagulant MP