International collaboration as a tool for diagnosis of patients with inherited thrombocytopenia in the setting of a developing country

Background: Inherited thrombocytopenias (IT) are heterogeneous genetic disorders which frequently represent a diagnostic challenge. 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. Methods: 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, and included platelet glycoprotein expression, immunofluorescence for myosin-9 in granulocytes and platelet thrombospondin-1 and molecular screening of candidate genes. Results: Thirty-one patients from 14 pedigrees were included, age was 32 (4-72) years, platelet count was 72 (4-147) x10(9) /L. Autosomal dominant inheritance was found in 9 (64%) pedigrees, 10 (71%) had large platelets and 9 (29%) patients presented with syndromic forms. A definitive diagnosis was made in 10 of 14 pedigrees and comprised MYH9-related disease in 4, 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 1 pedigree each. Conclusions: 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. © 2012 International Society on Thrombosis and Haemostasis.