Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation
Background: The bleeding disorder described here is due to a heterozygous autosomal dominant C1611>A variant in the thrombomodulin (TM) gene that significantly elevates plasma TM levels, which enhances the activation of protein C. This activation inhibits factors VIIIa and Va, reducing thrombin g...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | Research and Practice in Thrombosis and Haemostasis |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2475037925000020 |
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| author | Serge Pierre-Louis Johalene Rabout Octavio Labrada Fatima Radouani Emeline Chonville Beatrice Ferrey Olivier Pierre-Louis Yesim Dargaud |
| author_facet | Serge Pierre-Louis Johalene Rabout Octavio Labrada Fatima Radouani Emeline Chonville Beatrice Ferrey Olivier Pierre-Louis Yesim Dargaud |
| author_sort | Serge Pierre-Louis |
| collection | DOAJ |
| description | Background: The bleeding disorder described here is due to a heterozygous autosomal dominant C1611>A variant in the thrombomodulin (TM) gene that significantly elevates plasma TM levels, which enhances the activation of protein C. This activation inhibits factors VIIIa and Va, reducing thrombin generation and potentially leading to severe hemorrhagic manifestations. Key Clinical Question: What is the bleeding profile of patients with this rare condition? What are the most frequent clinical signs, and how can they be treated? Clinical Approach: We present a case study of an index patient with the TM C1611>A variant and his 20 family members. We detail the hemostatic strategies employed during various bleeding episodes and surgical procedures. Conclusion: Sharing clinical experiences is crucial for hematologists managing similar cases, as it provides valuable insights into effective treatment strategies. |
| format | Article |
| id | doaj-art-1f0924d6e3b14dbc89bc2df10bf4a920 |
| institution | Kabale University |
| issn | 2475-0379 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Research and Practice in Thrombosis and Haemostasis |
| spelling | doaj-art-1f0924d6e3b14dbc89bc2df10bf4a9202025-02-02T05:29:08ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-01-0191102678Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutationSerge Pierre-Louis0Johalene Rabout1Octavio Labrada2Fatima Radouani3Emeline Chonville4Beatrice Ferrey5Olivier Pierre-Louis6Yesim Dargaud7Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France, Martinique; Correspondence Serge Pierre-Louis, Centre de Ressources et de Compétences, Maladies Hémorragiques Constitutionnelles, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France, Martinique.Centre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France, MartiniqueCentre Hospitalier Universitaire de la Martinique, Hôpital Pierre Zobda Quitman, Service de Chirurgie Orthopédique, Fort-de-France, MartiniqueUR5_3 Pathologies cardiaques, toxicités environnementales et envenimations, Université des Antilles, Hôpital Pierre Zobda Quitman, Fort-de-France, MartiniqueCentre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France, MartiniqueCentre de Ressources et de Compétences des Maladies Hémorragiques Constitutionnelles, CHU de Martinique, Hôpital Pierre Zobda Quitman, Fort-de-France, MartiniqueUR5_3 Pathologies cardiaques, toxicités environnementales et envenimations, Université des Antilles, Hôpital Pierre Zobda Quitman, Fort-de-France, MartiniqueCentre de Référence de l’Hémophilie, Unité d'Hémostase Clinique, Hôpital Cardiologique Louis Pradel, Université Lyon I, Lyon, FranceBackground: The bleeding disorder described here is due to a heterozygous autosomal dominant C1611>A variant in the thrombomodulin (TM) gene that significantly elevates plasma TM levels, which enhances the activation of protein C. This activation inhibits factors VIIIa and Va, reducing thrombin generation and potentially leading to severe hemorrhagic manifestations. Key Clinical Question: What is the bleeding profile of patients with this rare condition? What are the most frequent clinical signs, and how can they be treated? Clinical Approach: We present a case study of an index patient with the TM C1611>A variant and his 20 family members. We detail the hemostatic strategies employed during various bleeding episodes and surgical procedures. Conclusion: Sharing clinical experiences is crucial for hematologists managing similar cases, as it provides valuable insights into effective treatment strategies.http://www.sciencedirect.com/science/article/pii/S2475037925000020bleedingC1611>Ap.Cys537Stopplatelet transfusionrecombinant activated factor VII (rFVIIa)thrombomodulin (TM) |
| spellingShingle | Serge Pierre-Louis Johalene Rabout Octavio Labrada Fatima Radouani Emeline Chonville Beatrice Ferrey Olivier Pierre-Louis Yesim Dargaud Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation Research and Practice in Thrombosis and Haemostasis bleeding C1611>A p.Cys537Stop platelet transfusion recombinant activated factor VII (rFVIIa) thrombomodulin (TM) |
| title | Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation |
| title_full | Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation |
| title_fullStr | Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation |
| title_full_unstemmed | Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation |
| title_short | Clinical management of bleeding manifestations in a family with the thrombomodulin C1611>A (p.Cys537Stop) mutation |
| title_sort | clinical management of bleeding manifestations in a family with the thrombomodulin c1611 a p cys537stop mutation |
| topic | bleeding C1611>A p.Cys537Stop platelet transfusion recombinant activated factor VII (rFVIIa) thrombomodulin (TM) |
| url | http://www.sciencedirect.com/science/article/pii/S2475037925000020 |
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