Case Report: Laboratory detection of a thrombotic tendency in a family with hypodysfibrinogenemia and a novel FGG mutation.

Autor:	Monard A; Department of Internal Medicine-Hematology, Maastricht University Medical Centre+, Maastricht, Netherlands.; CARIM, School for Cardiovascular Disease, Maastricht University, Maastricht, Netherlands., Castoldi E; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands., De Simone I; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands., Wichapong K; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands., van Duijl T; Department of Molecular Hematology, Sanquin Research, Amsterdam, Netherlands., van den Biggelaar M; Department of Molecular Hematology, Sanquin Research, Amsterdam, Netherlands., Spada S; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands.; Centre for Thrombosis and Hemostasis (CTH), University Medical Centre Mainz, Mainz, Germany., van Doorn W; Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, Netherlands., Hellenbrand D; Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, Netherlands., van der Meijden P; CARIM, School for Cardiovascular Disease, Maastricht University, Maastricht, Netherlands.; Thrombosis Expertise Center, Heart+ Vascular Center, Maastricht University Medical Center+, Maastricht, Netherlands., Swieringa F; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands., Stork A; Department of Internal Medicine, Anna Hospital, Geldrop, Netherlands., Ten Cate H; Department of Biochemistry, CARIM, Maastricht University, Maastricht, Netherlands.; Department of Internal Medicine, Maastricht University, Maastricht, Netherlands., Beckers E; Department of Internal Medicine-Hematology, Maastricht University Medical Centre+, Maastricht, Netherlands., Heubel-Moenen F; Department of Internal Medicine-Hematology, Maastricht University Medical Centre+, Maastricht, Netherlands., Henskens Y; CARIM, School for Cardiovascular Disease, Maastricht University, Maastricht, Netherlands.; Department of Molecular Hematology, Sanquin Research, Amsterdam, Netherlands.
Jazyk:	angličtina
Zdroj:	Frontiers in cardiovascular medicine [Front Cardiovasc Med] 2024 Oct 15; Vol. 11, pp. 1488602. Date of Electronic Publication: 2024 Oct 15 (Print Publication: 2024).
DOI:	10.3389/fcvm.2024.1488602
Abstrakt:	Introduction: Hypodysfibrinogenemia is a rare congenital fibrinogen disorder (CFD) which may induce thrombotic and bleeding events. Therefore, patient management needs careful evaluation. Routine coagulation tests are inadequate to predict the clinical phenotype. Clinical Findings: A 60-year-old woman with both bleeding and thrombotic complications and her two daughters were referred to our center for genotypic and phenotypic analysis of a CFD. Diagnosis: Conventional laboratory results led to the diagnosis of hypodysfibrinogenemia in all three subjects. They all carried the same heterozygous c.1124A>G mutation in FGG resulting in p.Tyr375Cys amino acid substitution, which was confirmed by protein variant analysis from plasma. In silico structure analysis predicted possible conformational and functional changes of the fibrinogen molecule. Thrombin generation indicated a hypercoagulable state confirmed by microfluidics that showed enhanced fibrin formation in both daughters, regardless of the coagulation trigger. Conclusion: We report on a family with hypodysfibrinogenemia and a novel FGG heterozygous missense mutation, possibly leading to conformational changes or covalent dimerization. Thrombin generation and particularly microfluidic measurements disclosed a hypercoagulable state, which was not detected with routine coagulation tests, justifying a different patient management. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (© 2024 Monard, Castoldi, De Simone, Wichapong, van Duijl, van den Biggelaar, Spada, van Doorn, Hellenbrand, van der Meijden, Swieringa, Stork, ten Cate, Beckers, Heubel-Moenen and Henskens.)
Databáze:	MEDLINE
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