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. Hence, we sought to investigate platelet subfractions and the platelet lipidome in patients with acute PE and concomitant vs absent RV distress.
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 characterized via HPLC-ESI-QTOF-MS/MS.
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 individualize antithrombotic therapy and thus improve RV function in PE patients.
Figure 1: Percentage of platelet subpopulations in PE patients with (n=28) and without (n=12) RV distress, and healthy controls (n=8)
Figure 2: Radar chart showing significantly altered (log2 FC) lipids in patients with PE
Figure 3: Correlation of platelet subpopulations and platelet lipidome in the overall cohort of patients with PE (n=40)
