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

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

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 (Ks), 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 Ks, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). An increase of lactate levels by 1 mM leading to the prolongation of CLT by 8.82 min 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.

Highlights

Acute pulmonary embolism (PE), isolated or combined with deep-vein thrombosis (DVT), is the major cause of mortality or hospitalization due to venous thromboembolism (VTE) [1]
We have shown for the first time that lactate levels ≥2 mM in acute PE patients are associated with impaired plasma fibrinolytic capacity accompanied by enhanced neutrophil extracellular trap (NET) formation and increased thrombin generation
In line with previous studies [3,7,8], we observed that lactate levels ≥2 mM are related to right ventricular (RV) dysfunction and positive troponin T (TnT), and they can predict intermediate–high mortality risk in acute PE

Summary

Introduction

Acute pulmonary embolism (PE), isolated or combined with deep-vein thrombosis (DVT), is the major cause of mortality or hospitalization due to venous thromboembolism (VTE) [1]. Increased lactate levels have been proposed as a prognostic marker in sepsis [6]. 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. Elevated lactate levels were associated with more prothrombotic fibrin properties as reflected by 11% reduced Ks, 13% longer CLT, along with 11% increased ETP. Lactate levels were positively associated with plasma citH3 concentrations, ETP, CLT, and PAI-1 (p < 0.05). 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

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