Introduction

Patients with chronic obstructive pulmonary disease (COPD) are at increased risk for cardiovascular events, particularly following an acute exacerbation (AE-COPD). Exacerbations are associated with increased systemic inflammation, which may drive coagulation. This prospective cohort study aimed to determine how an AE-COPD affects platelet activation, the endothelium, plasmatic coagulation and fibrinolysis, and its association with systemic inflammation.

Materials and methods

Fifty-two patients with an AE-COPD were included. Blood samples at admission, at day 3 of treatment and at convalescence were available for 32 patients. Platelet-monocyte complex (PMC) formation, monocyte Mac-1 expression and platelet (re)activity (P-selectin expression, αIIbβ3 activation) were measured by flow cytometry. Von Willebrand Factor (VWF), thrombin generation (TG) and clot lysis time (CLT) were determined as measures of endothelial activation, plasmatic coagulation and fibrinolysis, respectively.

Results

Exacerbations were associated with increased PMCs (MFI 31.3 vs 23.8, p = 0.004) and Mac-1 (MFI 38.2 vs 34.8, p = 0.006) compared to convalescence, but not with changes in platelet (re)activity. VWF (antigen, activity, active fraction) and TG (peak, ETP and velocity index) were all significantly higher during AE-COPD compared to convalescence. PMCs, Mac-1, VWF and TG were positively associated with systemic inflammation (CRP). CLT was prolonged in AE-COPD patients with systemic inflammation. Moreover, platelet hyperreactivity on admission was associated with an increased risk for exacerbation relapse.

Conclusions

Acute exacerbations are associated with an inflammation-associated prothrombotic state, characterized by increased PMCs, endothelial activation and plasmatic coagulation. Our findings provide direction for future studies on biomarkers predicting the risk of exacerbation relapse and cardiovascular events.

中文翻译：

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COPD的急性加重通过血小板-单核细胞复合物，内皮细胞活化和凝血酶生成增加与血栓前状态相关。

介绍

患有慢性阻塞性肺疾病（COPD）的患者发生心血管事件的风险增加，尤其是在急性加重（AE-COPD）之后。病情加重与全身炎症反应加剧有关，全身炎症反应可能导致凝血。这项前瞻性队列研究旨在确定AE-COPD如何影响血小板活化，内皮细胞，血浆凝结和纤维蛋白溶解及其与全身炎症的关系。

材料和方法

包括52例AE-COPD患者。入院时，治疗第3天和恢复期的血液样本可供32名患者使用。通过流式细胞术测量血小板-单核细胞复合物（PMC）的形成，单核细胞Mac-1表达和血小板（反应）活性（P-选择蛋白表达，αIIbβ3活化）。冯·威勒布兰德因子（VWF），凝血酶生成（TG）和凝块溶解时间（CLT）被分别确定为内皮细胞活化，血浆凝结和纤维蛋白溶解的量度。

结果

与恢复期相比，病情恶化与PMC升高（MFI 31.3 vs 23.8，p = 0.004）和Mac-1（MFI 38.2 vs 34.8，p = 0.006）相关，但与血小板活性无关。与恢复期相比，AE-COPD期间的VWF（抗原，活性，活性级分）和TG（峰值，ETP和速度指数）均显着较高。PMC，Mac-1，VWF和TG与全身性炎症（CRP）正相关。AE-COPD全身性炎症患者的CLT延长。此外，入院时血小板反应过度与恶化复发的风险增加有关。

结论

急性加重与炎症相关的血栓形成前状态有关，其特征在于PMC增加，内皮细胞活化和血浆凝结。我们的发现为今后关于生物标志物的研究提供了方向，这些标志物预测了病情加重复发和心血管事件的风险。