Inherited platelet disorders
Inherited platelet disorders
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DOI：
10.1111/j.1365-2516.2012.02856.x
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发表时间：
2012-07-01
期刊：
影响因子：
3.9
通讯作者：
Seligsohn, U.
中科院分区：
文献类型：
--
作者：
Nurden, A. T.;Freson, K.;Seligsohn, U.
。当血小板在血管损伤时无法发挥其止血功能时，巨核细胞谱系的遗传性疾病会导致出血。血小板缺陷包括粘附（GPIb-IX-V、BernardSoulier 综合征）或聚集受体（整合素 aIIb beta 3、Glanzmann 血小板无力）缺失或功能障碍，以及可溶性激动剂的主要受体、储存细胞器的分泌、激活途径和促凝血活性的产生的缺陷。在 ChediakHigashi、HermanskyPudlak、WiskottAldrich 和 Scott 综合征等疾病中，分子损伤会延伸至其他细胞。在家族性血小板减少症 (FT) 中，血小板产生的数量不足以确保止血。一些 FT 影响血小板形态并引起巨血小板综合征（例如 MYH9 相关疾病），伴有骨髓内巨核细胞成熟的变化和血小板过早释放。血小板生成疾病也可能影响其他细胞，并在某些情况下干扰主要器官的发育和/或功能。血小板疾病的诊断需要血小板功能测试，研究通常通过流式细胞术、荧光和电子显微镜对受体进行定量分析来辅助。包括全外显子组测序在内的新一代基于 DNA 的程序提供了令人兴奋的新视角。血小板输注仍然是严重出血的最常见治疗方法，去氨加压素治疗通常用于轻度疾病。替代疗法包括 rFVIIa 和血小板生成素类似物用于 FT 的潜在用途。干细胞或骨髓移植已成功治疗多种疾病，而基因治疗在 WiskottAldrich 综合征中显示出希望。
. Inherited diseases of the megakaryocyte lineage give rise to bleeding when platelets fail to fulfill their hemostatic function upon vessel injury. Platelet defects extend from the absence or malfunctioning of adhesion (GPIb-IX-V, BernardSoulier syndrome) or aggregation receptors (integrin aIIb beta 3, Glanzmann thrombasthenia) to defects of primary receptors for soluble agonists, secretion from storage organelles, activation pathways and the generation of procoagulant activity. In disorders such as the ChediakHigashi, HermanskyPudlak, WiskottAldrich and Scott syndromes the molecular lesion extends to other cells. In familial thrombocytopenia (FT), platelets are produced in insufficient numbers to assure hemostasis. Some FT affect platelet morphology and give rise to the giant platelet syndromes (e.g. MYH9-related diseases) with changes in megakaryocyte maturation within the bone marrow and premature release of platelets. Diseases of platelet production may also affect other cells and in some cases interfere with development and/or functioning of major organs. Diagnosis of platelet disorders requires platelet function testing, studies often aided by the quantitative analysis of receptors by flow cytometry and fluorescence and electron microscopy. New generation DNA-based procedures including whole exome sequencing offer an exciting new perspective. Transfusion of platelets remains the most common treatment of severe bleeding, management with desmopressin is often used for mild disorders. Substitute therapies are available including rFVIIa and the potential use of thrombopoietin analogues for FT. Stem cell or bone marrow transplanation has been successful for several diseases while gene therapy shows promise in the WiskottAldrich syndrome.