Hereditary thrombocytopenia with platelet sialic acid deficiency and mutations in the GNE genes.

BACKGROUND: The inherited macrothrombocytopenias are rare disorders and the underlying cause can be identified in many cases but in some, this can remain enigmatic. Platelet transfusions are often administered during hemorrhagic events. METHODS: A patient with previously unexplained inherited macrothrombocytopenia with a platelet count between 3-20 × 109 /L is described in which studies were performed using exome sequencing (ES) and platelet flow cytometry. RESULTS: Both the hemoglobin and white cell counts were normal. ES revealed two suspicious variants, one likely pathogenic and one a variant of uncertain significance, in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, and flow cytometry showed diminished expression of surface platelet sialic acid (about 5%) but normal red cell sialic acid. The Thrombopoietin (TPO) level was low, and the patient responded to TPO-mimetic treatment with an increase in the platelet count. CONCLUSION: Two variants in the GNE gene were able to be upgraded to pathogenic with apparently restricted expression to the megakaryocyte lineage. Platelet transfusion may be avoided in these patients with TPO-mimetic treatment.

Patient-centered approach to managing factor XIII deficiency.

Factor XIII (FXIII) is a thrombin-activated protransglutaminase that plays a key role in blood clot formation. Congenital FXIII A-subunit deficiency represents a rare bleeding disorder that affects one in 2-3 million individuals worldwide and is treated with recombinant FXIII (rFXIII). However, due to the rarity of the disease, clinicians are often left to weigh individual variation in FXIII activity and/or symptoms to optimally guide dosing. Cases often become further complicated when patients experience refractory bleeding, which can be difficult to treat. This report describes an approach to rFXIII dosing in two patients who required deviation from standard protocols to maintain therapeutic FXIII troughs. We highlight limitations in our understanding of FXIII deficiency management, while also providing an example of the application of pharmacokinetic data to individualise therapy for improved outcomes. Finally, the case reminds us of the importance of patient-centered, cost-conscious care and multidisplinary teamwork in complex cases.