Department of Hematology Research, Instituto de Investigaciones Médicas Alfredo Lanari, University of Buenos Aires, CONICET, Buenos Aires, Argentina.
J Thromb Haemost. 2012 Aug;10(8):1653-61. doi: 10.1111/j.1538-7836.2012.04805.x.
Inherited thrombocytopenias (ITs) are heterogeneous genetic disorders that frequently represent a diagnostic challenge. The requirement of highly specialized tests for diagnosis represents a particular problem in resource-limited settings. To overcome this difficulty, we applied a diagnostic algorithm and developed a collaboration program with a specialized international center in order to increase the diagnostic yield in a cohort of patients in Argentina.
Based on the algorithm, initial evaluation included collection of clinical data, platelet size, blood smear examination and platelet aggregation tests. Confirmatory tests were performed according to diagnostic suspicion, which included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes.
Thirty-one patients from 14 pedigrees were included; their median age was 32 (4-72) years and platelet count 72 (4-147)×10(9) L(-1). Autosomal dominant inheritance was found in nine (64%) pedigrees; 10 (71%) had large platelets and nine (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in four, while classic and monoallelic Bernard-Soulier syndrome, gray platelet syndrome, X-linked thrombocytopenia, thrombocytopenia 2 (ANKRD26 mutation) and familial platelet disorder with predisposition to acute myelogenous leukemia were diagnosed in one pedigree each.
Adoption of an established diagnostic algorithm and collaboration with an expert referral center proved useful for diagnosis of IT patients in the setting of a developing country. This initiative may serve as a model to develop international networks with the goal of improving diagnosis and care of patients with these rare diseases.
遗传性血小板减少症（ITs）是一种异质性遗传疾病，常构成诊断挑战。诊断所需的高度专业化测试在资源有限的环境中是一个特殊问题。为了克服这一困难，我们应用了一种诊断算法，并与一个专门的国际中心建立了合作计划，以提高阿根廷患者队列的诊断率。
根据该算法，初始评估包括收集临床数据、血小板大小、血涂片检查和血小板聚集试验。根据诊断可疑性进行确认性测试，包括血小板糖蛋白表达、粒细胞肌球蛋白-9 的免疫荧光、血小板血小板反应蛋白-1 和候选基因的分子筛选。
共纳入 14 个家系的 31 例患者；其中位年龄为 32（4-72）岁，血小板计数为 72（4-147）×10（9）/L。9 个（64%）家系存在常染色体显性遗传；10 个（71%）有大血小板，9 个（29%）患者表现为综合征形式。14 个家系中有 10 个作出了明确诊断，包括 4 个 MYH9 相关疾病，1 个经典和单等位基因伯纳德-苏利耶综合征、灰色血小板综合征、X 连锁血小板减少症、血小板减少症 2（ANKRD26 突变）和家族性血小板倾向急性髓细胞白血病。
采用既定的诊断算法并与专家转诊中心合作，对于发展中国家 IT 患者的诊断非常有用。这一举措可作为建立国际网络的典范，以改善这些罕见疾病患者的诊断和治疗。
