A shift in the platelet lipidome affects platelet differentiation into distinct subfractions in patients with acute pulmonary embolism
J Henes, T Harm, M Friedel, R Stuebenrath, Z Laspa, D Schaale, V Dicenta-Baunach, A K Rohlfing, K Mueller, Z Xu, X Fu, M Laemmerhofer, T Geisler, M Gawaz, D RathAbstract
Introduction
Severity of pulmonary embolism (PE) is significantly driven by right ventricular (RV) failure and thrombus composition which possibly alters susceptibility towards therapy. Following platelet activation, platelets differentiate into different phenotypes, including a procoagulant and an aggregatory phenotype. Differentiation into these phenotypes may be orchestrated by changes in the platelet lipidome.
Purpose
We sought to investigate platelet subfractions and the platelet lipidome in patients with acute PE and concomitant vs absent RV distress. Hence, our aim was to determine whether these parameters interact with each other and potentially have functional relevance in acute PE.
Methods
We examined isolated platelets from 48 patients with acute PE. PE and RV distress were diagnosed with CT pulmonary angiogram (CTPA) and transthoracic echocardiography, respectively. We identified platelet subpopulations based on platelet surface exposure of CD42b, phosphatidylserine and GPIIb/IIIa using flow cytometry. Additionally, the platelet lipidome was characterised via HPLC-ESI-QTOF-MS/MS. Information on a cohort of healthy controls was also provided.
Results
In patients with RV distress, we found higher levels of aggregatory (p=0.021) and lower levels of procoagulant platelets (p=0.033) when compared to patients without RV dysfunction. Moreover, we found a significant upregulation of cholesteryl esters, triglycerides and fatty acids in patients with RV dysfunction. Finally, these lipids correlated significantly with levels of aggregatory and procoagulant platelets in the overall cohort of patients.
Conclusion
Alterations in the platelet lipidome may affect differentiation of platelets into distinct subfractions in PE. These subfractions possibly affect thrombus composition and efficacy of therapy thus influencing RV distress. Consequently, distribution of platelet subfractions may help to individualise antithrombotic therapy and thus improve RV function in PE patients.Figure 1For image description, please refer to the figure legend and surrounding text.Figure 2For image description, please refer to the figure legend and surrounding text.