CO107 | PREGNANCY IN A YOUNG WOMAN WITH SEVERE THROMBOCYTOPENIA ASSOCIATED WITH GNE GENE MUTATION

S. Bonafini¹, A. Meneguzzi¹, A. Savoia², S. Uccella³, V. Tamborrino³, S. Cesaro³, E. Bonetti³, A. Giuffrida⁴, P. Minuz¹, C. Fava¹ | ¹Dip. Medicina, Azienda Ospedaliera Universitaria Integrata Verona, Italy; ²Dip di Ingegneria per la Medicina di innovazione, Università di Verona, Italy; ³Dip. Materno-Infantile, Azienda Ospedaliera Universitaria Integrata Verona, Italy; ⁴Dip. Medicina trasfusionale, Azienda Ospedaliera Universitaria Integrata Verona, Italy

Background. The GNE gene encodes UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase, a rate-limiting enzyme involved in the biosynthesis of sialic acid. Pathogenic GNE variants can cause GNE-related thrombocytopenia and/or myopathy. The clinical management of pregnant patients with a GNE gene mutation is not defined, nor are the risks and methods for minimizing bleedings associated with this condition, especially during childbirth.
Case Report. We report a young woman with a homozygous GNE mutation (p.Gly590Arg) presenting with severe thrombocytopenia and a moderate muco-cutaneous hemorrhagic syndrome, with some major hemorrhages (epistaxis since childhood and heavy menstrual bleeding) (ISTH-BAT: 13). Thrombocytopenia was evident from the first days of life (6–10×10⁹ platelets/L) and had previously been misdiagnosed as immune thrombocytopenia. Standard treatments for immune thrombocytopenia were ineffective, with the exception of eltrombopag, which elicited a prompt increase in circulating platelets (30 to 60×10⁹ platelets/L). The hemorrhagic phenotype improved over the years. At 21 years of age, the patient became pregnant while not receiving any pharmacological treatment. No change in hemorrhagic diathesis was observed, and clinical monitoring was therefore decided during the first two trimesters of pregnancy. The mean platelet count during pregnancy ranged from 11 to 34 × 10⁹/L. Pregnancy was complicated by gestational diabetes. To minimize the risk of delivery-related hemorrhage, eltrombopag (25 mg/day) was initiated at 34 weeks of gestation, resulting in an increase in platelet count to 47–51 × 10⁹/L without any adverse event. The management of delivery was decided on a multidisciplinary basis (platelet transfusion and use of tranexamic acid and rFVIIa in the event of severe bleeding were recommended). Labor was induced at 38 weeks, and delivery occurred without hemorrhagic or thrombotic complications in either the mother or the newborn. Eltrombopag withdrawal during puerperium and lactation was followed by a prompt reduction in circulating platelets (27 × 10⁹ platelets/L) with a 76% immature platelet fraction. The assessment of platelet phenotype and function by flow cytometry revealed increased expression of activated GPIIb/IIIa, reduced GPIbα, and increased binding of Annexin V (procoagulant platelets) in resting platelets, as well as a diminished response to platelet agonists (both secretion and glycoprotein expression).
Conclusions. Eltrombopag, administered in this case of GNE-related thrombocytopenia before the pregnancy and during the third gestational trimester, was both effective and safe. To our knowledge, this is the first report describing the use of eltrombopag in a patient with GNE-related thrombocytopenia. The present case and our findings indicate that thrombocytopenia is associated with indices of elevated platelet turnover and platelet activation, which may contribute to platelet removal and may partly justify the discrepancy between severely reduced platelet counts and relatively mild bleeding symptoms. Further studies are needed to better characterize the observed platelet functional abnormalities and the basis of clinical heterogeneity in this rare condition.