Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial.
Platelet desialylation is a novel mechanism and a therapeutic target in thrombocytopenia during sepsis: an open-label, multicenter, randomized controlled trial.
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血小板去唾液酸化是脓毒症期间血小板减少症的一种新机制和治疗靶点：一项开放标签、多中心、随机对照试验
DOI：
10.1186/s13045-017-0476-1
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发表时间：
2017-05-11
影响因子：
28.5
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Li MF;Li XL;Fan KL;Yu YY;Gong J;Geng SY;Liang YF;Huang L;Qiu JH;Tian XH;Wang WT;Zhang XL;Yu QX;Zhang YF;Lin P;Wang LN;Li X;Hou M;Liu LY;Peng J
小鼠模型研究表明，血小板去唾液酸化是脓毒症期间血小板减少的重要机制。首先，我们进行了一项前瞻性、多中心、观察性研究，纳入患有或不患有血小板减少症的脓毒症患者，以确定脓毒症、严重脓毒症和脓毒症休克患者中血小板去唾液酸化与血小板减少症之间的关联。选择性别和年龄匹配的健康成年人作为血小板脱唾液酸水平分析的正常对照（研究 I）。接下来，我们进行了一项开放标签随机对照试验（RCT），将严重脓毒症合并血小板减少症患者（血小板计数≤50 × 109/L）按1：1的比例随机分配接受单独抗菌治疗（对照组）或抗菌治疗加奥司他韦（奥司他韦组）（研究II）。主要结局是研究开始时的血小板去唾液酸化水平、随机化后 14 天内的总体血小板反应率以及随机化后 28 天内的全因死亡率。次要结局包括血小板恢复时间、出血事件的发生以及随机分组后 14 天内输注的血小板量。与 134 名无血小板减少症的患者相比，127 名患有血小板减少症的脓毒症患者的血小板去唾液酸化水平显着升高。奥司他韦组 54 名患者中有 45 名（83.3%）出现血小板反应，而对照组 52 名患者中有 34 名（65.4%；P = 0.045）。奥司他韦组的中位血小板恢复时间为 5 天（四分位距 4-6），而对照组为 7 天（四分位距 5-10）（P = 0.003）。与对照组相比，奥司他韦组输注的血小板数量显着减少（P = 0.044）。无论是否使用奥司他韦，总体 28 天死亡率没有差异。序贯器官衰竭评估评分和血小板恢复时间是奥司他韦治疗的独立指标。所有死亡的主要原因是多器官衰竭。脓毒症患者血小板减少症与血小板去唾液酸化增加有关。添加奥司他韦可显着提高血小板反应率，缩短血小板恢复时间，减少血小板输注。中国临床试验注册中心，ChiCTR-IPR-16008542。本文的在线版本 (doi:10.1186/s13045-017-0476-1) 包含补充材料，可供授权用户使用。
Studies in murine models suggested that platelet desialylation was an important mechanism of thrombocytopenia during sepsis. First, we performed a prospective, multicenter, observational study that enrolled septic patients with or without thrombocytopenia to determine the association between platelet desialylation and thrombocytopenia in patients with sepsis, severe sepsis, and septic shock. Gender- and age-matched healthy adults were selected as normal controls in analysis of the platelet desialylation levels (study I). Next, we conducted an open-label randomized controlled trial (RCT) in which the patients who had severe sepsis with thrombocytopenia (platelet counts ≤50 × 109/L) were randomly assigned to receive antimicrobial therapy alone (control group) or antimicrobial therapy plus oseltamivir (oseltamivir group) in a 1:1 ratio (study II). The primary outcomes were platelet desialylation level at study entry, overall platelet response rate within 14 days post-randomization, and all-cause mortality within 28 days post-randomization. Secondary outcomes included platelet recovery time, the occurrence of bleeding events, and the amount of platelets transfused within 14 days post-randomization. The platelet desialylation levels increased significantly in the 127 septic patients with thrombocytopenia compared to the 134 patients without thrombocytopenia. A platelet response was achieved in 45 of the 54 patients in the oseltamivir group (83.3%) compared with 34 of the 52 patients in the control group (65.4%; P = 0.045). The median platelet recovery time was 5 days (interquartile range 4–6) in the oseltamivir group compared with 7 days (interquartile range 5–10) in the control group (P = 0.003). The amount of platelets transfused decreased significantly in the oseltamivir group compared to the control group (P = 0.044). There was no difference in the overall 28-day mortality regardless of whether oseltamivir was used. The Sequential Organ Failure Assessment score and platelet recovery time were independent indicators of oseltamivir therapy. The main reason for all of the mortalities was multiple-organ failure. Thrombocytopenia was associated with increased platelet desialylation in septic patients. The addition of oseltamivir could significantly increase the platelet response rate, shorten platelet recovery time, and reduce platelet transfusion. Chinese Clinical Trial Registry, ChiCTR-IPR-16008542. The online version of this article (doi:10.1186/s13045-017-0476-1) contains supplementary material, which is available to authorized users.