Blood:预防性抗凝或可降低镰状细胞病血管阻塞性危象的发病率

2020-02-04 QQY MedSci原创

血管阻塞性危象(VOC)是镰状细胞病(SCD)发病和住院的主要原因。但目前只有三种治疗方法(羟基脲、l-谷氨酰胺和crizanlizumab)被批准用于治疗SCD。这些药物限制了血管阻塞性危象的持续时间、严重程度和发生频率。凝血激活是SCD的一个标志。对SCD动物模型的研究表明,凝血可导致慢性炎症和与SCD相关的终末器官损伤。但凝血是否直接导致引发VOC的微血管停滞仍是不明确。在本研究中,研究人员

血管阻塞性危象(VOC)是镰状细胞病(SCD)发病和住院的主要原因。但目前只有三种治疗方法(羟基脲、l-谷氨酰胺和crizanlizumab)被批准用于治疗SCD。这些药物限制了血管阻塞性危象的持续时间、严重程度和发生频率。凝血激活是SCD的一个标志。

对SCD动物模型的研究表明,凝血可导致慢性炎症和与SCD相关的终末器官损伤。但凝血是否直接导致引发VOC的微血管停滞仍是不明确。

在本研究中,研究人员发现,VOC小鼠模型中,抑制组织因子(TF)和下调凝血蛋白酶,Xa因子和凝血酶,可显著减轻血色素诱导的微血管淤滞。

用药物抑制主要凝血酶受体、蛋白酶激活受体-1 (PAR-1)以及所有非造血细胞的PAR-1缺陷,也均可减少镰状细胞病小鼠模型的瘀血。PAR-1缺陷与内皮细胞血管性血友病因子(vWF)表达减少有关;vWF已被证明可介导微血管停滞。此外,TF抑制可减少由小动脉中性粒细胞-血小板微栓子介导的镰状小鼠肺血管闭塞。

总之,上述结果提示预防性抗凝或可降低VOC的发病率。

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