Platelet mitochondrial membrane depolarization reflects disease severity in patients with preeclampsia

Thrombocytopenia is a feared complication of preeclampsia (PE) that can additionally complicate the disease course and that carries a poor prognosis. The disease mechanisms of PE on a platelet level are poorly understood and only few platelet-based markers have been investigated. In sepsis, platelet mitochondrial membrane depolarization, a sensitive and early indicator of mitochondrial dysfunction and platelet cell death, correlates with disease severity and outcome as shown in previous studies. The aim of this study was to investigate platelet mitochondrial membrane potential (Mmp-Index) by flow-cytometry in patients with preeclampsia compared to controls and to assess its value in correlation with disease severity of PE and during follow-up after delivery.

In this prospective translational case-control study, platelet Mmp-Index was measured in PE (n = 16) by flow cytometry in living platelets in simultaneous comparison to healthy pregnant (n = 32) and non-pregnant controls (n = 16) and was individually reassessed after delivery to investigate recovery of platelet mitochondrial function. Subgroup analysis of patients with severe and non-severe PE was performed. Six patients with isolated gestational hypertension were also included for comparative analysis.

Platelet Mmp-Index in patients with symptomatic preeclampsia (Mmp-Index non-severe PE 0.72 ([0.591; 0.861]; p = 0.002) was significantly reduced compared to healthy pregnant controls (Mmp-Index 0.97 [0.795; 1.117]) and even more pronounced in patients with severe PE (n = 6) (Mmp-Index severe PE 0.542 [0.361; 0.623]; p = 0.03). In the severe PE group, complementary measurements of platelet Annexin V- and CD62 (P-Selectin) surface expression showed apoptosis of platelet populations in the majority of patients. Platelet Mmp normalized after delivery within few days. Patients with isolated gestational hypertension showed normal Mmp-Index values.

This study shows for the first time that platelet Mmp-Index is a quantifiable, easy-to-measure intracellular marker of platelet mitochondrial function in vital cells that reflects disease severity of preeclampsia. For future investigations, platelet Mmp may serve as a prognostic marker that may aid clinical risk stratification and adds novel information on potential mechanisms for thrombocytopenia in preeclampsia.