Abstract Number: PB1014
Meeting: ISTH 2021 Congress
Background: Inherited platelet function disorders (IPFD) are qualitative platelet diseases with mild to severe bleeding, whose diagnosis can be a challenge. Familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML) is an IPFD caused by germline mutations in the gene encoding the transcription factor RUNX1. Dysregulated expression of RUNX1-targets in platelets, including downregulation of the α2 subunit (GPIa) of collagen receptor α2β1, has been proposed to guide diagnosis.
Aims: We present a case of a woman with mild thrombocytopenia and severe bleeding whose laboratory study led to the diagnosis of FPD/AML.
Methods: Platelets were evaluated by morphometric, functional (PFA-200, lumiaggregometry), flow cytometry (glycoprotein expression), and genetic (NGS) studies.
Results: The patient, a 32 years-old-woman, bleeding score (ISTH-BAT) of 10, was first evaluated at 10-years-old because of mucocutaneous bleeding and severe hemorrhage after tonsillectomy requiring red blood cell transfusion; moderate thrombocytopenia with storage-pool deficiency was assumed. There was no family history of hemorrhagic diseases or hematological neoplasms. About twenty years later, during pregnancy, she underwent a new evaluation. Laboratory studies showed moderate thrombocytopenia (87×109/L), extended PFA-200 EPI and ADP closure times (>300s), impaired platelet aggregations, absent in response to COL (1µg/mL) and decreased in response to ADP (10µM), EPI (10µM), and AA (1mM), but normal in response to TRAP-6 (25µM); reduced ristocetin (1mg/mL) induced agglutination. ATP release was absent with ADP, COL, EPI, and AA, and decreased with TRAP-6. Platelet glycoprotein levels were normal except for CD49b/GpIa (28%). A likely pathogenic frameshift variant in RUNX1 (c.358del; p.Ala120Profs*2) was identified by NGS.
Conclusions: In this case, a bleeding tendency more severe than expected to the degree of thrombocytopenia, together with a storage pool platelet dysfunction and low platelet GpIa expression, warned for a possible FPD/AML. NGS assisted the diagnosis, by revealing a likely pathogenic RUNX1 variant.
To cite this abstract in AMA style:Sousa-Pimenta M, Pereira M, Lau C, Gonçalves A, Oliveira ME, Cruz E, Santos R, Lima M, Morais S. Long-term Severe Platelet Dysfunction as a Form of Presentation of Familial Platelet Disorder with Predisposition to Acute Myeloid Leukemia (FPD/AML), due to a RUNX1 Variant [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/long-term-severe-platelet-dysfunction-as-a-form-of-presentation-of-familial-platelet-disorder-with-predisposition-to-acute-myeloid-leukemia-fpd-aml-due-to-a-runx1-variant/. Accessed December 5, 2021.
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