Tiffany Pascreau1,2, Maria E de la Morena-Barrio3, Dominique Lasne1,2, Mercedes Serrano4,5, Elsa Bianchini2, Manoelle Kossorotoff6, Nathalie Boddaert7,8, Arnaud Bruneel9, Nathalie Seta9, Vicente Vicente3, Pascale de Lonlay10, Javier Corral3, Delphine Borgel1,2. 1. Laboratoire d'Hématologie, AP-HP, Hôpital Necker-Enfants malades, Paris, France. 2. INSERM UMR-S1176, Le Kremlin-Bicêtre, France. 3. Servicio de Hematología y Oncología Médica, Centro Regional de Hemodonación, Hospital Universitario Morales Meseguer, Universidad de Murcia, IMIB-Arrixaca, CIBERER, Murcia, Spain. 4. Department of Pediatric Neurology, Institute of Pediatric Research-Hospital Sant Joan de Déu, U-703 Center for Biomedical Research on Rare Diseases, Barcelona, Spain. 5. Department of Genetic Medicine, Institute of Pediatric Research-Hospital Sant Joan de Déu, U-703 Center for Biomedical Research on Rare Diseases, Barcelona, Spain. 6. Paediatric Neurology Department, French Center for Paediatric Stroke, AP-HP, Hôpital Necker-Enfants-Malades, Paris, France. 7. Pediatric Radiology Department, AP-HP, Hôpital Necker-Enfants-Malades, Paris, France. 8. Institut Imagine, INSERM U1000 and UMR 1163, Paris, France. 9. Biochimie Métabolique, AP-HP, Hôpital Bichat-Claude Bernard, Paris, France. 10. Reference Center of Metabolism, Imagine Institute, AP-HP, Hôpital Necker-Enfants Maladies, University Paris-Descartes, Paris, France.
Abstract
BACKGROUND: Congenital disorders of glycosylation are rare inherited diseases affecting many different proteins. The lack of glycosylation notably affects the hemostatic system and leads to deficiencies of both procoagulant and anticoagulant factors. OBJECTIVE: To assess the hemostatic balance in patients with multiple coagulation disorders by using a thrombin generation assay. METHOD: We performed conventional coagulation assays and a thrombin generation assay on samples from patients with congenital disorder of glycosylation. The thrombin generation assay was performed before and after activation of the protein C system by the addition of soluble thrombomodulin. RESULTS: A total of 35 patients were included: 71% and 57% had low antithrombin and factor XI levels, respectively. Protein C and protein S levels were abnormally low in 29% and 26% of the patients, respectively, whereas only 11% displayed low factor IX levels. Under baseline conditions, the thrombin generation assay revealed a significantly higher endogenous thrombin potential and thrombin peak in patients, relative to controls. After spiking with thrombomodulin, we observed impaired involvement of the protein C system. Hence, 54% of patients displayed a hypercoagulant phenotype in vitro. All the patients with a history of stroke-like episodes or thrombosis displayed this hypercoagulant phenotype. CONCLUSION: A thrombin generation assay revealed a hypercoagulant in vitro phenotype under baseline condition; this was accentuated by impaired involvement of the protein C system. This procoagulant phenotype may thus reflect the risk of severe vascular complications. Further research will have to determine whether the thrombin generation assay is predictive of vascular events.
BACKGROUND:Congenital disorders of glycosylation are rare inherited diseases affecting many different proteins. The lack of glycosylation notably affects the hemostatic system and leads to deficiencies of both procoagulant and anticoagulant factors. OBJECTIVE: To assess the hemostatic balance in patients with multiple coagulation disorders by using a thrombin generation assay. METHOD: We performed conventional coagulation assays and a thrombin generation assay on samples from patients with congenital disorder of glycosylation. The thrombin generation assay was performed before and after activation of the protein C system by the addition of soluble thrombomodulin. RESULTS: A total of 35 patients were included: 71% and 57% had low antithrombin and factor XI levels, respectively. Protein C and protein S levels were abnormally low in 29% and 26% of the patients, respectively, whereas only 11% displayed low factor IX levels. Under baseline conditions, the thrombin generation assay revealed a significantly higher endogenous thrombin potential and thrombin peak in patients, relative to controls. After spiking with thrombomodulin, we observed impaired involvement of the protein C system. Hence, 54% of patients displayed a hypercoagulant phenotype in vitro. All the patients with a history of stroke-like episodes or thrombosis displayed this hypercoagulant phenotype. CONCLUSION: A thrombin generation assay revealed a hypercoagulant in vitro phenotype under baseline condition; this was accentuated by impaired involvement of the protein C system. This procoagulant phenotype may thus reflect the risk of severe vascular complications. Further research will have to determine whether the thrombin generation assay is predictive of vascular events.
Authors: Rawan H Hareeri; Mohammed M Aldurdunji; Hossam M Abdallah; Ali A Alqarni; Shaimaa G A Mohamed; Gamal A Mohamed; Sabrin R M Ibrahim Journal: Molecules Date: 2022-10-10 Impact factor: 4.927
Authors: María Eugenia de la Morena-Barrio; María Sabater; Belén de la Morena-Barrio; Renee L Ruhaak; Antonia Miñano; José Padilla; Mara Toderici; Vanessa Roldán; Juan R Gimeno; Vicente Vicente; Javier Corral Journal: Mol Genet Genomic Med Date: 2020-06-12 Impact factor: 2.183