Phosphatidylserine-exposing blood cells and microparticles induce procoagulant activity in non-valvular atrial fibrillation. (1st May 2018)

• Record Type: Journal Article
• Authors: Wang, Lixiu; Bi, Yayan; Yu, Muxin; Li, Tao; Tong, Dongxia; Yang, Xiaoyan; Zhang, Cong; Guo, Li; Wang, Chunxu; Kou, Yan; Dong, Zengxiang; Novakovic, Valerie A.; Tian, Ye; Kou, Junjie; Shammas, Masood A.; Shi, Jialan
• Is Part Of: International journal of cardiology. Volume 258(2018)
• Page Start: 138
• Page End: 143
• Publication Date: 2018-05-01
• Subjects: PS phosphatidylserine -- NVAF non-valvular atrial fibrillation -- MPs microparticles -- PCA procoagulant activity -- RDW red cell distribution width -- PMPs platelet-derived MPs -- EMPs endothelial-derived MPs -- LMPs leukocyte-derived MPs -- WBC white blood cell -- RBC red blood cell -- MDP MP-depleted plasma -- TF tissue factor -- PT prothrombin time -- APTT activated partial thromboplastin time -- NMPs neutrophils-derived MPs -- MMPs monocyte-derived MPs -- ErMPs erythrocyte-derived MPs -- PLT platelet; Non valvular atrial fibrillation -- Phosphatidylserine -- Blood cell -- Microparticle -- Procoagulant activity; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2018.01.116
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: 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). Methods: 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. Results: 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). Conclusions: 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. Highlights: PS + blood cells and MPs are significantly higher in both NVAF than those in controls. PS + blood cells and MPs contribute to markedly increased PCA in NVAF patients. Blockade of exposed PS with lactadherin significantly inhibits PCA in NVAF patients. The levels of PS + platelets and MPs are positively correlated with thrombus diameter.