CLINICAL AND LABORATORIAL CHARACTERIZATION OF A COHORT OF PATIENTS WITH HEREDITARY PLATELET DISORDERS

Abstract

Introduction: Inherited Platelet Disorders (IPDs) are rare conditions characterized by altered platelet function (IPFDs) and/or reduced platelet counts (IPNDs). Diagnosing IPDs is challenging, with frequent misdiagnoses and unappropriated treatment. In low and middle-income countries data on these disorders are scarce. Objective: To describe a cohort of IPD patients at a reference center in Brazil. Material and methods: A descriptive analysis was conducted on patients with suspected or diagnosed IPDs at the Thrombosis and Hemostasis outpatient clinic of the Hospital das Clínicas, University of São Paulo, Brazil. From 857 patients identified between 1998 and 2023, 60 met the eligibility criteria for suspected or confirmed IPDs. Those with acquired causes of platelet dysfunction were excluded. Results: There were 60 patients, 65% with IPFDs and 35% IPNDs. Women were 75%, with a median age of 48-years. In the IPND group, 62% had a family history of thrombocytopenia. In the IPFD group, family history was positive in 51% of cases. Previous misdiagnoses included ITP and von Willebrand disease, with 38% of patients receiving prior treatment for ITP with corticosteroids (38%) or splenectomy (10%). IPND group had marked thrombocytopenia and IPFD group had normal or slightly reduced platelet counts. The median mean platelet volume (MPV) was 14.1 fL for the IPND group and 11.1 fL for the IPFD group, 75% of the IPND patients had altered MPV. Platelet immunophenotyping was performed in 27 patients (45%), 15 (55%) exhibited abnormal results. Platelet aggregation tests were conducted in 34 cases (57%), 27 (79%) had altered platelet aggregation, but discordant results were noted in eight (30%) of the altered tests. Lastly, platelet secretion tests were performed in 16 patients (27%). Bleeding phenotype was assessed with the ISTH BAT score, showing a median of 6. Median BAT score was 10 in IPFD and 3.5 in the IPND group. Syndromic features were present in 10% of patients. A total of 47 patients (78%) needed treatment during follow-up, including 43% of patients in the IPND group and 97% in the IPFD group. The most used treatments were antifibrinolytics (73%) and platelet transfusions (55%). Discussion: Diagnosis of IPDs is challenging and many cases remain unrecognized. Among patients with IPNDs, up to 30% receive an incorrect diagnosis of ITP. Similar results were found in our cohort. A key factor in the investigation of IPDs is a family history of thrombocytopenia or increased bleeding, which was present in more than 50% of the cohort in both subgroups. Platelet macrocytosis was more common in IPNDs, being another helpful diagnostic marker in this subgroup. Data regarding platelet morphology could not be obtained due to the lack of reporting standardization. Discordant results in platelet aggregation tests were attributed to pre-analytical factors. The IPFD group exhibits a more severe hemorrhagic phenotype, while BAT score in IPNDs was commonly low. Concerning management, IPFD group underwent more therapeutic interventions, possibly due to a higher bleeding tendency. Conclusions: Identifying IPDs is essential for proper treatment and follow-up. Careful assessment of the familial history, bleeding risk and the platelet count, morphology and function are crucial for diagnosing IPDs, particularly in settings without access to advanced genetic testing. This study provides insights into the characteristics and management of IPDs in centers with limited resources.