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A novel method to quantify fibrin-fibrin and fibrin-α2-antiplasmin cross-links in thrombi formed from human trauma patient plasma.
Morrow, Gael B; Flannery, Sarah; Charles, Philip D; Heilig, Raphael; Feller, Timea; McQuilten, Zoe; Wake, Elizabeth; Ariens, Robert A S; Winearls, James; Mutch, Nicola J; Fischer, Roman; Laffan, Mike A; Curry, Nicola.
Afiliación
  • Morrow GB; School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, United Kingdom; Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Aberdeen Cardiovascular and Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, Un
  • Flannery S; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Charles PD; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Heilig R; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Feller T; Leeds Thrombosis Collective, Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom.
  • McQuilten Z; Transfusion Research Unit, Monash University, Melbourne and Monash Health, Melbourne, Australia.
  • Wake E; Trauma Service, Gold Coast University Hospital, University of Queensland, Southport, Queensland, Australia; School of Medicine, University of Queensland, Southport, Queensland, Australia.
  • Ariens RAS; Leeds Thrombosis Collective, Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, United Kingdom.
  • Winearls J; School of Medicine, University of Queensland, Southport, Queensland, Australia; Intensive Care Unit, Gold Coast University Hospital, Southport, Queensland, Australia; Australia and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Victoria, Australia.
  • Mutch NJ; Aberdeen Cardiovascular and Diabetes Centre, School of Medicine, Medical Sciences and Nutrition, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
  • Fischer R; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
  • Laffan MA; Centre for Haematology, Imperial College London, London, United Kingdom.
  • Curry N; Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom; Oxford Haemophilia and Thrombosis Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
J Thromb Haemost ; 22(6): 1758-1771, 2024 Jun.
Article en En | MEDLINE | ID: mdl-38462220
ABSTRACT

BACKGROUND:

The widespread use of the antifibrinolytic agent, tranexamic acid (TXA), interferes with the quantification of fibrinolysis by dynamic laboratory assays such as clot lysis, making it difficult to measure fibrinolysis in many trauma patients. At the final stage of coagulation, factor (F)XIIIa catalyzes the formation of fibrin-fibrin and fibrin-α2-antiplasmin (α2AP) cross-links, which increases clot mechanical strength and resistance to fibrinolysis.

OBJECTIVES:

Here, we developed a method to quantify fibrin-fibrin and fibrin-α2AP cross-links that avoids the challenges posed by TXA in determining fibrinolytic resistance in conventional assays.

METHODS:

Fibrinogen alpha (FGA) chain (FGA-FGA), fibrinogen gamma (FGG) chain (FGG-FGG), and FGA-α2AP cross-links were quantified using liquid chromatography-mass spectrometry (LC-MS) and parallel reaction monitoring in paired plasma samples from trauma patients prefibrinogen and postfibrinogen replacement. Differences in the abundance of cross-links in trauma patients receiving cryoprecipitate (cryo) or fibrinogen concentrate (Fg-C) were analyzed.

RESULTS:

The abundance of cross-links was significantly increased in trauma patients postcryo, but not Fg-C transfusion (P < .0001). The abundance of cross-links was positively correlated with the toughness of individual fibrin fibers, the peak thrombin concentration, and FXIII antigen (P < .05).

CONCLUSION:

We have developed a novel method that allows us to quantify fibrin cross-links in trauma patients who have received TXA, providing an indirect measure of fibrinolytic resistance. Using this novel approach, we have avoided the effect of TXA and shown that cryo increases fibrin-fibrin and fibrin-α2AP cross-linking when compared with Fg-C, highlighting the importance of FXIII in clot formation and stability in trauma patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Tranexámico / Heridas y Lesiones / Fibrinógeno / Fibrina / Alfa 2-Antiplasmina / Fibrinólisis / Antifibrinolíticos Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ácido Tranexámico / Heridas y Lesiones / Fibrinógeno / Fibrina / Alfa 2-Antiplasmina / Fibrinólisis / Antifibrinolíticos Límite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: J Thromb Haemost Asunto de la revista: HEMATOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido