Hemostatic defects in congenital disorders of glycosylation

Abstract

A “state of the Art” lecture titled “Hemostatic Defects in Congenital Disorders of Glycosylation” was presented at the ISTH 2022 congress. Congenital disorders of glycosylation (CDGs) are rare, inherited, metabolic diseases. The diagnosis of CDG is often challenging due to the broad variety of disorders, the variable level of severity, and phenotypic heterogeneity. Most CDGs are multisystem disorders, and neurologic involvement is frequent. Patients with CDG often present coagulation abnormalities characterized by low levels of procoagulant or anticoagulant factors. Antithrombin deficiency is frequently associated with factor XI deficiency and less frequently with a protein C, protein S, or factor IX deficiency. This coagulation profile differs from those observed in liver failure, disseminated intravascular coagulation, and vitamin K deficiency, and so, should prompt the physician to consider a diagnosis of CDG. Coagulopathy can lead to thrombotic and/or hemorrhagic complications. In patients with phosphomannomutase 2 deficiency (the most common CDG), thrombotic events are more frequent than hemorrhagic events. In other types of CDGs, both hemorrhagic and thrombotic events have been described. Overall, the hemostatic balance in these patients is precarious and necessitates close monitoring in a setting of acute illness with greater metabolic needs. Here, we review the most relevant hemostatic defects observed in CDG and their clinical implications. Finally, we summarize relevant new data on this topic presented at the ISTH 2022 congress.