Skip to main content

CASE REPORT article

Front. Cardiovasc. Med.
Sec. Thrombosis and Haemostasis
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1488602

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

Provisionally accepted
Amaury Monard Amaury Monard 1,2Elisabetta Castoldi Elisabetta Castoldi 2,3Ilaria De Simone Ilaria De Simone 4*Kanin Wichapong Kanin Wichapong 2,4Tirsa T. Van Duijl Tirsa T. Van Duijl 5Maartje Van Den Biggelaar Maartje Van Den Biggelaar 5Stefano Spada Stefano Spada 2*William P. Van Doorn William P. Van Doorn 6Dave Hellenbrand Dave Hellenbrand 6*Paola van der Meijden Paola van der Meijden 2,4Frauke Swieringa Frauke Swieringa 2,4Alexander D. Stork Alexander D. Stork 7*Hugo Ten Cate Hugo Ten Cate 2,4Erik Beckers Erik Beckers 6*Floor Heubel- Moenen Floor Heubel- Moenen 6*Yvonne Henskens Yvonne Henskens 6
  • 1 Department of Internal Medicine - Hematology, Maastricht University Medical Centre, Maastricht, Netherlands
  • 2 School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands, Netherlands
  • 3 Department of Biochemistry, Maastricht University, Maastricht, Netherlands
  • 4 Maastricht University, Maastricht, Netherlands
  • 5 Sanquin Research, Amsterdam, Netherlands
  • 6 Maastricht University Medical Centre, Maastricht, Limburg, Netherlands
  • 7 Sint Anna Hospital, Oss, Netherlands

The final, formatted version of the article will be published soon.

    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.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.

    Keywords: Congenital fibrinogen disorders, hypodysfibrinogenemia, diagnosis, phenotype, case report

    Received: 30 Aug 2024; Accepted: 26 Sep 2024.

    Copyright: © 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. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Ilaria De Simone, Maastricht University, Maastricht, 6211 LK, Netherlands
    Stefano Spada, School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, 6229 ER, Netherlands, Netherlands
    Dave Hellenbrand, Maastricht University Medical Centre, Maastricht, 6229 HX, Limburg, Netherlands
    Alexander D. Stork, Sint Anna Hospital, Oss, Netherlands
    Erik Beckers, Maastricht University Medical Centre, Maastricht, 6229 HX, Limburg, Netherlands
    Floor Heubel- Moenen, Maastricht University Medical Centre, Maastricht, 6229 HX, Limburg, Netherlands

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.