OBJECTIVES: 

To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO).

DESIGN: 

Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019.

SETTING: 

The PICU in a large tertiary referral pediatric ECMO center.

PATIENTS: 

Eighty-seven neonates and children (< 18 yr) supported by ECMO.

INTERVENTIONS: 

None.

MEASUREMENTS AND MAIN RESULTS: 

Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3–8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10–29 d) and 35 days (IQR, 19–75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020).

CONCLUSIONS: 

The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.

中文翻译：

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血小板表型和功能随着体外膜氧合持续时间的增加而变化

目标： 

研究与儿科体外膜肺氧合 (ECMO) 相关的血小板病理生理学。

设计： 

对2016年9月1日至2019年12月31日新生儿和儿童ECMO患者的前瞻性观察研究。

环境： 

大型三级转诊儿科 ECMO 中心的 PICU。

患者： 

87 名新生儿和儿童（< 18 岁）接受 ECMO 支持。

干预措施： 

没有任何。

测量和主要结果： 

在 ECMO 第 1、2 和 5 天收集动脉血样本，并通过全血流式细胞术进行分析。还记录了每位患者相应的临床数据。总共招募了 87 名患者（中位年龄，65 天；四分位数范围 [IQR]，7 天至 4 岁）。ECMO 的中位持续时间为 5 天（IQR，3-8 天），在 PICU 和医院的中位住院时间分别为 18 天（IQR，10-29 天）和 35 天（IQR，19-75 天） 。根据先验确定的定义，42 名患者 (48%) 至少发生过一次大出血，12 名患者 (14%) 在 ECMO 期间至少发生过一次血栓事件。从 ECMO 第 2 天到第 5 天，血小板纤维蛋白原受体表达下降（中位荧光强度 [MFI]，29,256 vs 26,544；p = 0.0005），而冯维勒布兰德因子表达增加（MFI：7,620 vs 8,829；p = 0.0459）。通过与抗 P-选择素、PAC-1（结合激活的 GPIIb/IIIa）和抗 CD63 单克隆抗体的结合来测量，血小板对激动剂凝血酶受体激活肽 6 的反应从 ECMO 的第 2 天到第 5 天也有所下降（P-选择素曲线下面积[AUC]：分别为63.46 vs 42.82，p = 0.0022；PAC-1 AUC：93.75 vs 74.46，p = 0.0191；CD63 AUC：55.69 vs 41.76，p = 0.0020）。

结论： 

随着时间的推移，血小板反应的丧失可能会导致 ECMO 期间出血。这些新颖的见解可能有助于了解儿科 ECMO 的出血机制，并且临床上监测血小板标志物可以预测或早期发现出血和血栓形成。