Abstract

Background: Rare coagulation disorders represent 3–5% of all inherited coagulation deficiencies and are usually inherited as autosomal recessive. Oman has high rate of consanguineous marriages; we aimed to study the prevalence, presentation and management in affected Omani children. Materials and Methods: Retrospective study in pediatric patients with rare coagulation disorders in a tertiary hospital in Oman from 2009 to 2020. Results: Rare coagulation disorders were diagnosed in 79 patients (39 males/40 females), aged 1 day to 13 years, accounting for 24.7% (79/319) of all children with inherited coagulation disorders; remainder included patients with hemophilia and von Willebrand disease. FXI deficiency was most common with prevalence of 39.2%, followed by fibrinogen disorders 32.9%, FVII 18.9%, FV 5%, FXIII 2.5%, and FX deficiencies 1.2%. Manifestations ranged from mild to serious to rare/atypical; presentation at birth, ruptured-hemorrhagic ovarian cyst, splenic laceration-rupture, and sight-threatening retrobulbar-intraocular hemorrhage. Intracranial hemorrhage (ICH) occurred in 9/79 patients, it was initial mode of presentation in seven of them. Global developmental delay as a complication occurred in three. Standardized treatment strategies were used with prophylaxis initiation early in life in severely affected children. Conclusions: This ethnic group demonstrated unique features in terms of: heterogenous/atypical presentations; severe manifestations in moderate phenotype hypofibrinogenemia; clinical severity and laboratory phenotype correlation in FV deficiency; poor association between factor activity level and bleeding severity in FVII deficiency and severe bleeding tendency despite moderate laboratory phenotype in FXIII deficiency. We recommend multicenter collaboration to identify the genotype-phenotype correlation and therapeutic options of such rare, yet serious disorders.

摘要

背景：罕见的凝血障碍占所有遗传性凝血缺陷的 3-5%，通常以常染色体隐性遗传。阿曼的近亲结婚率很高；我们旨在研究受影响的阿曼儿童的患病率、表现和管理。材料与方法：对阿曼一家三级医院 2009 年至 2020 年患有罕见凝血障碍的儿科患者进行回顾性研究。结果：79例患者（39男/40女）被诊断为罕见凝血障碍，年龄1天至13岁，占所有遗传性凝血障碍患儿的24.7%（79/319）；其余包括血友病和血管性血友病患者。FXI 缺乏症最常见，患病率为 39.2%，其次是纤维蛋白原疾病 32.9%、FVII 18.9%、FV 5%、FXIII 2.5% 和 FX 缺乏症 1.2%。表现范围从轻微到严重到罕见/非典型；出生时的表现，破裂出血性卵巢囊肿，脾裂伤-破裂和危及视力的球后-眼内出血。9/79 名患者发生颅内出血 (ICH)，其中 7 名患者出现颅内出血 (ICH)。全球发育迟缓作为并发症发生在三个。结论：这个种族群体在以下方面表现出独特的特征：异质/非典型表现；中度表型低纤维蛋白原血症的严重表现; FV缺乏症的临床严重程度和实验室表型相关性；尽管 FXIII 缺乏症的实验室表型适中，但 FVII 缺乏症的因子活性水平与出血严重程度之间的关联性较差，以及严重的出血倾向。我们建议进行多中心合作，以确定这种罕见但严重的疾病的基因型-表型相关性和治疗选择。