L'Institut de Rhythmologie et Modélisation Cardiaque (LIRYC), Plateforme Technologique et d'Innovation Biomédicale, Hôpital Xavier Arnozan, Pessac, France.
Br J Haematol. 2014 Apr;165(2):165-78. doi: 10.1111/bjh.12662. Epub 2013 Nov 29.
Genetic defects of platelets constitute rare diseases that include bleeding syndromes of autosomal dominant, recessive or X-linked inheritance. They affect platelet production, resulting in a low circulating platelet count and changes in platelet morphology, platelet function, or a combination of both with altered megakaryopoiesis and a defective platelet response. As a result, blood platelets fail to fulfil their haemostatic function. Most studied of the platelet function disorders are deficiencies of glycoprotein mediators of adhesion and aggregation while defects of primary receptors for stimuli include the P2Y12 ADP receptor. Studies on inherited defects of (i) secretion from storage organelles (dense granules, α-granules), (ii) the platelet cytoskeleton and (iii) the generation of pro-coagulant activity have identified genes indirectly controlling the functional response. Signalling pathway defects leading to agonist-specific modifications of platelet aggregation are the current target of exome-sequencing strategies. We now review recent advances in the molecular characterization of platelet function defects.
血小板遗传缺陷构成了罕见疾病，包括常染色体显性、隐性或 X 连锁遗传的出血综合征。它们影响血小板的产生，导致循环血小板计数降低，血小板形态、血小板功能发生变化，或两者兼有，伴有巨核细胞生成异常和血小板反应缺陷。结果，血小板不能发挥其止血功能。研究最多的血小板功能障碍是黏附素和聚集的糖蛋白介质的缺乏，而刺激的主要受体缺陷包括 P2Y12 ADP 受体。对（i）储存细胞器（致密颗粒、α 颗粒）的分泌、（ii）血小板细胞骨架和（iii）促凝活性的产生的遗传性缺陷的研究确定了间接控制功能反应的基因。导致激动剂特异性血小板聚集改变的信号通路缺陷是外显子组测序策略的当前目标。我们现在回顾血小板功能缺陷的分子特征的最新进展。
