Division of Hematology and Oncology, Department of Pediatrics, University of California San Diego, La Jolla, CA; Rady Children's Institute of Genomic Medicine, San Diego, CA.
Rady Children's Institute of Genomic Medicine, San Diego, CA.
J Pediatr. 2023 Jun;257:113323. doi: 10.1016/j.jpeds.2022.12.036. Epub 2023 Jan 13.
To characterize the bleeding phenotype in Noonan syndrome (NS), to test the utility of following national guidelines in detecting this phenotype, to evaluate thromboelastography (TEG) as a diagnostic tool, and to evaluate the cohort for genotype-phenotype correlations.
Participants with a clinical diagnosis of NS or related RASopathies were enrolled in a cohort study. Study procedures included clinical bleeding assessment, coagulation testing per guidelines, and hematology consultation. TEG was completed in a subset, and genetic testing was conducted for those without a molecular diagnosis. International Society of Haemostasis and Thrombosis Bleeding Assessment Tool scores were calculated with hematology consultation. Bleeding phenotype was defined as abnormal bleeding score.
Twenty participants were enrolled; 12 completed clinical and laboratory evaluation, and five of whom met the definition for bleeding phenotype. Four of the five participants with a bleeding phenotype had platelet aggregation defects and at least one additional coagulation defect. TEG was performed in nine participants, four with bleeding phenotype and five without, and results were normal in all cases. No genotype-phenotype correlation was found.
Five of the 20 participants had a bleeding phenotype identified. Based on available data, we do not recommend incorporating TEG into clinical practice for patients with NS. Platelet aggregation defects were the most common abnormalities, which would not be detected on tier 1 testing of current guidelines; therefore, we propose a new algorithm.
描述诺南综合征（NS）的出血表型，检验遵循国家指南检测该表型的实用性，评估血栓弹力图（TEG）作为诊断工具的价值，并对该队列进行基因型-表型相关性评估。
患有临床诊断的 NS 或相关 RAS 相关疾病的参与者被纳入队列研究。研究程序包括临床出血评估、按指南进行凝血检测以及血液学咨询。在亚组中完成 TEG，对无分子诊断的患者进行基因检测。国际血栓止血协会出血评估工具评分通过血液学咨询计算。出血表型定义为异常出血评分。
共纳入 20 名参与者；12 名完成了临床和实验室评估，其中 5 名符合出血表型的定义。在具有出血表型的 5 名参与者中，有 4 名存在血小板聚集缺陷，且至少有另外一项凝血缺陷。在 9 名参与者中进行了 TEG，其中 4 名有出血表型，5 名没有，所有病例的结果均正常。未发现基因型-表型相关性。
在 20 名参与者中，有 5 名出现出血表型。根据现有数据，我们不建议将 TEG 纳入 NS 患者的临床实践。血小板聚集缺陷是最常见的异常，这将不会在当前指南的 1 级检测中被发现；因此，我们提出了一个新的算法。
