Kraemer Bjoern F, Hennis Irina, Karge Anne, Kraemer Anne Katrin, Dreyer Tobias F, Kiechle Marion, Kuschel Bettina, Bronger Holger
Medizinische Klinik Und Poliklinik I, LMU Klinikum, Munich, Germany.
Department of Gynecology and Obstetrics, Technical University of Munich, Ismaninger Str. 22, 81675, Munich, Germany.
Mol Med. 2022 May 4;28(1):51. doi: 10.1186/s10020-022-00472-x.
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.
血小板减少症是先兆子痫（PE）一种令人担忧的并发症，它会使疾病进程进一步复杂化且预后不良。目前对PE在血小板水平上的发病机制了解甚少，仅有少数基于血小板的标志物得到研究。在脓毒症中，血小板线粒体膜去极化是线粒体功能障碍和血小板细胞死亡的敏感且早期指标，如先前研究所示，它与疾病严重程度及预后相关。本研究的目的是通过流式细胞术检测先兆子痫患者的血小板线粒体膜电位（Mmp指数），并与对照组进行比较，同时评估其与PE疾病严重程度以及分娩后随访期间的相关性。
在这项前瞻性转化病例对照研究中，通过流式细胞术对16例PE患者的活血小板中的血小板Mmp指数进行检测，同时与32例健康孕妇和16例非孕对照进行比较，并在分娩后对患者个体进行重新评估，以研究血小板线粒体功能的恢复情况。对重度和非重度PE患者进行亚组分析。还纳入了6例单纯妊娠高血压患者进行对比分析。
有症状先兆子痫患者的血小板Mmp指数（非重度PE的Mmp指数为0.72[0.591；0.861]；p = 0.002）与健康孕妇对照组（Mmp指数为0.97[0.795；1.117]）相比显著降低，在重度PE患者（n = 6）中更为明显（重度PE的Mmp指数为0.5至42[0.361；0.623]；p = 0.03）。在重度PE组中，对血小板膜联蛋白V和CD62（P选择素）表面表达的补充检测显示，大多数患者的血小板群体存在凋亡。血小板Mmp在分娩后数天内恢复正常。单纯妊娠高血压患者的Mmp指数值正常。
本研究首次表明，血小板Mmp指数是活细胞中血小板线粒体功能的一种可量化、易于测量的细胞内标志物，可反映先兆子痫的疾病严重程度。在未来的研究中，血小板Mmp可作为一种预后标志物，有助于临床风险分层，并为先兆子痫血小板减少症的潜在机制提供新信息。
