Association between acute complications in PMM2-CDG patients and haemostasis anomalies: Data from a multicentric study and suggestions for acute management.

Objectives: Patients with PMM2-CDG develop acute events (stroke-like episodes (SLEs), thromboses, haemorrhages, seizures, migraines) associated with both clotting factors (factor XI) and coagulation inhibitors (antithrombin, protein C and protein S) deficiencies. The aim of the study was to correlate acute events to haemostasis and propose practical guidelines.
Methods: In this multicentric retrospective study, we evaluated clinical, radiological, haemostasis and electroencephalography data for PMM2-CDG patients hospitalized for acute events. Cerebral events were classified as thrombosis, haemorrhage, SLE, or "stroke mimic" (SM: normal brain imaging or evoking a migraine).
Results: Thirteen patients had a total of 31 acute episodes: 27 cerebral events with 7 SLEs, 4 venous thromboses, 4 haemorrhages (3 associated with thrombosis), 15 SMs at a mean age of 7.7 years; 4 non-cerebral thromboses, one of which included bleeding. A trigger was frequently involved (infection, head trauma). Although sometimes normal at baseline state, factor XI, antithrombin and protein C levels decreased during these episodes. No correlation between haemostasis anomalies and type of acute event was found.
Discussion: Acute events in PMM2-CDG are not negligible and are associated with haemostasis anomalies. An emergency protocol is proposed for their prevention and treatment (https://www.filiere-g2m.fr/urgences). For cerebral events, brain Magnetic Resonance Imaging with perfusion weight imaging and diffusion sequences, electroencephalogram and haemostasis protein levels guide the treatment: anticoagulation, antithrombin or fresh frozen plasma supplementation, antiepileptic therapy. Preventing bleeding and thrombosis is required in cases of surgery, prolonged immobilization, hormone replacement therapy.
Conclusion: Acute events in PMM2-CDG are associated with abnormal haemostasis, requiring practical guidance.
Competing Interests: Declaration of Competing Interest The authors Camille Wicker, Charles-Joris Roux, Louise Goujon, Yvan De Feraudy, Marie Hully, Anais Brassier, Claire-Marine Bérat, Nicole Chémaly, Arnaud Wiedemann, Lena Damaj, Marie-Thérèse Abi-Warde, Dries Dobbelaere, Agathe Roubertie, Aline Cano, Alina Arion, Anna Kaminska, Sabrina Da Costa, Arnaud Bruneel, Sandrine Vuillaumier, Nathalie Boddaert, Delphine Borgel, Tiffany Pascreau, Manoelle Kossorotoff, Annie Harroche, and P de Lonlay declare that they have no conflict of interest.
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