Calcaterra Ilenia Lorenza, Santoro Renata, Vitelli Nicoletta, Cirillo Ferdinando, D'Errico Guido, Guerrino Cornelia, Cardiero Giovanna, Di Taranto Maria Donata, Fortunato Giuliana, Iannuzzo Gabriella, Di Minno Matteo Nicola Dario
Department of Clinical Medicine and Surgery, Federico II University of Naples, 80131 Naples, Italy.
Department of Molecular Medicine and Medical Biotechnology, Federico II University of Naples, 80131 Naples, Italy.
Biomedicines. 2024 Sep 4;12(9):2017. doi: 10.3390/biomedicines12092017.
The antisense oligonucleotide against APOC3 mRNA volanesorsen was recently introduced to treat Familial Chylomicronemia Syndrome (FCS). Cases of decreased platelet count are reported among patients treated with volanesorsen. The aim of the study was to evaluate platelet function and thrombin generation (TG) assessment in FCS patients receiving volanesorsen. We performed a cross-sectional study on FCS patients treated with volanesorsen.
Changes in platelet count PLC were assessed from baseline to Tw12 and Tw36. To assess TG, samples were processed by CAT (with PPP-reagent LOW). The results were expressed by the thrombogram graphic (thrombin variation over time); LagTime; endogenous thrombin potential (ETP); peak; time to reach peak (ttpeak), StartTail and Velocity Index. Platelet aggregation was assessed by testing different agonists using the turbidimetry method.
Four FCS patients and four matched healthy controls were included in the present study. Changes in PLC were 30% at Tw12 and 34% at Tw36. Thrombin generation results showed values in the normal range (for patients and controls, respectively, LagTime:10.42 ± 4.40 and 9.25 ± 0.99; ttPeak:14.33 ± 4.01 and 13.10 ± 0.67; StartTail: 32.13 ± 3.54 and 29.46 ± 1.69; Velocity Index: 20.21 ± 3.63 and 33.05 ± 13.21; ETP: 599.80 ± 73.47 and 900.2 ± 210.99; peak value: 76.84 ± 1.07 and 123.30 ± 39.45) and no significant difference between cases and controls. Platelet aggregation test showed values in range, with no significant difference compared to healthy controls.
Our study showed for the first time that no significant changes in general hemostasis assessed by TG and in platelet function were observed in FCS patients receiving volanesorsen.
针对载脂蛋白C3（APOC3）mRNA的反义寡核苷酸volanesorsen最近被用于治疗家族性乳糜微粒血症综合征（FCS）。在接受volanesorsen治疗的患者中报告了血小板计数降低的病例。本研究的目的是评估接受volanesorsen治疗的FCS患者的血小板功能和凝血酶生成（TG）情况。我们对接受volanesorsen治疗的FCS患者进行了一项横断面研究。
评估从基线到Tw12和Tw36时血小板计数（PLC）的变化。为评估TG，样本用CAT（使用PPP - 试剂LOW）进行处理。结果通过血栓图（凝血酶随时间的变化）、LagTime（滞后时间）、内源性凝血酶潜力（ETP）、峰值、达到峰值的时间（ttpeak）、StartTail和速度指数来表示。使用比浊法通过测试不同激动剂来评估血小板聚集。
本研究纳入了4例FCS患者和4例匹配的健康对照。Tw12时PLC变化为30%，Tw36时为34%。凝血酶生成结果显示在正常范围内（患者和对照的结果分别为，LagTime：10.42±4.40和9.25±0.99；ttPeak：14.33±4.01和13.10±0.67；StartTail：32.13±3.54和29.46±1.69；速度指数：20.21±3.63和33.05±13.21；ETP：599.80±73.47和900.2±210.99；峰值：76.84±1.07和123.30±39.45），病例与对照之间无显著差异。血小板聚集试验结果在正常范围内，与健康对照相比无显著差异。
我们的研究首次表明，接受volanesorsen治疗的FCS患者在通过TG评估的总体止血和血小板功能方面未观察到显著变化。
