Phosphatidylserine-exposing blood cells and microparticles induce procoagulant activity in non-valvular atrial...

The definitive role of phosphatidylserine (PS) in the prothrombotic state of non-valvular atrial fibrillation (NVAF) remains unclear. Our objectives were to study the PS exposure on blood cells and microparticles (MPs) in NVAF, and evaluate their procoagulant activity (PCA).

NVAF patients without (n = 60) and with left atrial thrombi (n = 18) and controls (n = 36) were included in our study. Exposed PS was analyzed with flow cytometry and confocal microscopy. PCA was evaluated using clotting time, factor Xa (FXa), thrombin and fibrin formation.

PS⁺ blood cells and MPs were significantly higher in NVAF patients without and with left atrial thrombi (both P < 0.01) than in controls. Patients with left atrial thrombi showed increased PS⁺ platelets, neutrophils, erythrocytes and MPs compared with patients without thrombi (all P < 0.05). Moreover, in patients with left atrial thrombi, MPs primarily originated from platelets (56.1%) followed by leukocytes (21.9%, including MPs from neutrophils, monocytes and lymphocytes), erythrocytes (12.2%) and endothelial cells (8.9%). Additionally, PS⁺ blood cells and MPs contributed to markedly shortened coagulation time and dramatically increased FXa/thrombin/fibrin (all P < 0.001) generation in both NVAF groups. Furthermore, blockade of exposed PS on blood cells and MPs with lactadherin inhibited PCA by approximately 80%. Lastly, we found that the amount of PS⁺ platelets and MPs was positively correlated with thrombus diameter (all p < 0.005).

Our results suggest that exposed PS on blood cells and MPs play a procoagulant role in NVAF patients. Blockade of PS prior to thrombus formation might be a novel therapeutic approach in these patients.