CD34+ 造血干细胞计数可预测镰状细胞病患儿血管事件的发生。

CD34+ Hematopoietic Stem Cell Count Is Predictive of Vascular Event Occurrence in Children with Sickle Cell Disease.

机构信息

Inserm UMR-S1140, Faculté de Pharmacie, Paris, France.

AP-HP, Child Neurology, French center for pediatric stroke, Hôpital Universitaire Necker-Enfants malades, 149 rue de Sèvres, 75015, Paris, France.

出版信息

Stem Cell Rev Rep. 2018 Oct;14(5):694-701. doi: 10.1007/s12015-018-9835-8.

DOI:10.1007/s12015-018-9835-8

PMID:29931411

Abstract

BACKGROUND/OBJECTIVES: Sickle cell disease (SCD) complications mostly result from vascular dysfunction, concerning systemic microvasculature and cerebral large vessels. The aim of this cohort study was to identify potential circulating biomarkers predictive for further vascular event occurrence in pediatric SCD.

METHODS

We consecutively enrolled 108 children with SCD at steady state, aged 3-18 years old (median 9.8 years). Hematology, coagulation, hemolysis, endothelial, platelet and vascular activation parameters were recorded at inclusion. Neurovascular and systemic vascular events were prospectively recorded during a mean follow-up period of 27 months.

RESULTS

Patients at steady state displayed significantly higher hemolysis and platelet activation markers, higher leukocyte, CD34+ hematopoietic stem cell and microvesicle counts, and a pro-coagulant profile compared to controls matched for age and ethnicity. Circulating endothelial cell or nucleosome level did not differ. During the follow-up period, 36 patients had at least one neurovascular (n = 12) or systemic vascular event (n = 25). In a multivariate model, high CD34+ cell count was the best predictor for the occurrence of a vascular event (OR 1.2 for 1000 cell/mL increase, 95% CI [1.049-1.4], p = 0.013, sensitivity 53%, specificity 84% for a threshold of 8675 cells/mL).

CONCLUSION

CD34+ cell count at steady state is a promising biomarker of further vascular event in children with SCD.

摘要

背景/目的：镰状细胞病（SCD）的并发症主要是由于血管功能障碍引起的，涉及全身微血管和脑大血管。本队列研究的目的是确定潜在的循环生物标志物，以预测小儿 SCD 中进一步血管事件的发生。

方法

我们连续纳入了 108 例处于稳定状态的 SCD 患儿，年龄 3-18 岁（中位数 9.8 岁）。在纳入时记录了血液学、凝血、溶血、内皮、血小板和血管激活参数。在平均 27 个月的随访期间，前瞻性记录神经血管和全身血管事件。

结果

与年龄和种族相匹配的对照组相比，稳定状态下的患者表现出明显更高的溶血和血小板激活标志物、更高的白细胞、CD34+造血干细胞和微囊泡计数，以及促凝谱。循环内皮细胞或核小体水平没有差异。在随访期间，36 名患者至少发生了一次神经血管（n=12）或全身血管事件（n=25）。在多变量模型中，高 CD34+细胞计数是发生血管事件的最佳预测因子（每增加 1000 个细胞/mL 的比值比为 1.2，95%可信区间为 [1.049-1.4]，p=0.013，敏感性为 53%，特异性为 84%，阈值为 8675 个细胞/mL）。