FLI1-related thrombocytopenia: piecing together the story Free

A 42-year-old woman with down-slanting palpebral fissures presented to clinic for lifelong thrombocytopenia (platelet count, 80 × 10⁹/L to 100 × 10⁹/L; mean platelet volume 11.4 fL) and recurrent, disproportionate bleeding while on warfarin for a mechanical valve. Platelet Function Analyzer-100 closure times were normal. Platelet aggregation studies showed reduced responses to arachidonic acid, collagen, and epinephrine, with preserved adenosine diphosphate and ristocetin responses. Platelet flow cytometry revealed decreased glycoprotein VI (55%, below 70% cutoff). A Giemsa-Wright-stained peripheral blood smear revealed normal platelets with rare hypogranular and/or giant platelets (panel A; 1000× magnification). Platelet whole-mount electron microscopy showed absence of dense granules (panel B; healthy control, panel C). Platelet thin-section electron microscopy showed decreased alpha granules (panel D) and occasional giant alpha granules (panel E; healthy control, panel F). Next-generation sequencing detected a heterozygous deletion of FLI1 (exons 1-9). The clinical, laboratory, and genetic features were consistent with a FLI1-related thrombocytopenia, prompting referral to a clinical geneticist for further evaluation.

In addition to controlling local sources of bleeding, platelet transfusions and antifibrinolytics as needed can aid hemostasis given the quantitative and qualitative defects. Moderate thrombocytopenia and/or anticoagulation can deceive clinicians into anchoring to them as fully explanative etiologies of otherwise disproportionate bleeding and forgoing more advanced testing. This case highlights that inherited platelet disorders can be difficult to diagnose, especially in adults, and require a high degree of clinical suspicion.

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