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急性肺栓塞中乳酸水平升高与血栓前纤维蛋白凝块特性相关:中性粒细胞胞外陷阱形成的作用

Elevated Lactate Levels in Acute Pulmonary Embolism Are Associated with Prothrombotic Fibrin Clot Properties: Contribution of NETs Formation.

作者信息

Ząbczyk Michał, Natorska Joanna, Janion-Sadowska Agnieszka, Malinowski Krzysztof P, Janion Marianna, Undas Anetta

机构信息

Institute of Cardiology, Jagiellonian University Medical College, 31-202 Krakow, Poland.

John Paul II Hospital, 31-202 Krakow, Poland.

出版信息

J Clin Med. 2020 Mar 30;9(4):953. doi: 10.3390/jcm9040953.

Abstract

BACKGROUND

Elevated plasma lactate levels correlate with high mortality rate in acute pulmonary embolism (PE) patients. We hypothesized that elevated lactate levels correlate with prothrombotic fibrin clot properties and enhanced neutrophil extracellular trap (NET) formation in acute PE.

METHODS

As many as 126 normotensive acute PE patients (aged 58 ± 14 years) were enrolled. Plasma fibrin clot permeability (K), clot lysis time (CLT), endogenous thrombin potential (ETP), citrullinated histone H3 (citH3), and plasminogen activator inhibitor-1 antigen (PAI-1), together with plasma L-lactate levels were evaluated on admission.

RESULTS

Lactate levels ≥2 mM were found in 70 (55.6%) patients in whom we observed 29% higher neutrophil count and 45% elevated plasma citH3 levels. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced K, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 ( < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 minutes was shown in the linear regression.

CONCLUSIONS

Our findings suggest a new mechanism contributing to a negative impact of elevated lactate levels on prognosis in acute PE patients, in particular hypofibrinolysis, associated with enhanced NET formation.

摘要

背景

急性肺栓塞(PE)患者血浆乳酸水平升高与高死亡率相关。我们推测,急性PE患者乳酸水平升高与血栓前纤维蛋白凝块特性及中性粒细胞胞外诱捕网(NET)形成增强有关。

方法

纳入126例血压正常的急性PE患者(年龄58±14岁)。入院时评估血浆纤维蛋白凝块通透性(K)、凝块溶解时间(CLT)、内源性凝血酶潜力(ETP)、瓜氨酸化组蛋白H3(citH3)、纤溶酶原激活物抑制剂-1抗原(PAI-1)以及血浆L-乳酸水平。

结果

70例(55.6%)患者乳酸水平≥2 mM,这些患者中性粒细胞计数高29%,血浆citH3水平升高45%。乳酸水平升高与血栓前纤维蛋白特性增加有关,表现为K降低11%、CLT延长13%以及ETP增加11%。乳酸水平与血浆citH3浓度、ETP、CLT和PAI-1呈正相关(<0.05)。线性回归显示,乳酸水平每升高1 mM,CLT延长8.82分钟。

结论

我们的研究结果提示了一种新机制,即乳酸水平升高对急性PE患者预后产生负面影响,尤其是与NET形成增强相关的纤维蛋白溶解功能减退。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae60/7231195/581defe10945/jcm-09-00953-g001.jpg

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