Review
Biochemistry & Molecular Biology
Machteld Sillen, Paul J. Declerck
Summary: TAFI, a proenzyme, is converted to a potent attenuator of the fibrinolytic system upon activation by thrombin, plasmin, or the thrombin/thrombomodulin complex. The development of molecules antagonizing TAFI function has gained much interest in the field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Karen Claesen, Joachim C. Mertens, Dorien Leenaerts, Dirk Hendriks
Summary: This paper provides an overview of Procarboxypeptidase U and related research, highlighting the novel concept of using CPU inhibitors as profibrinolytic agents, as well as the potential significance and clinical applications of CPU in thromboembolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Karen Claesen, Lynn Roth, Joachim C. Mertens, Karlijn Hermans, Yani Sim, Dirk Hendriks
Summary: Studies indicate that statins can reduce levels of procarboxypeptidase U in a cardiovascular disease model mouse, independent of their cholesterol-lowering effects, demonstrating a pleiotropic effect of statin treatment.
Article
Medicine, General & Internal
Karen Claesen, Yani Sim, An Bracke, Michelle De Bruyn, Emilie De Hert, Gwendolyn Vliegen, An Hotterbeekx, Alexandra Vujkovic, Lida van Petersen, Fien H. R. De Winter, Isabel Brosius, Caroline Theunissen, Sabrina van Ierssel, Maartje van Frankenhuijsen, Erika Vlieghe, Koen Vercauteren, Samir Kumar-Singh, Ingrid De Meester, Dirk Hendriks
Summary: The changes in CPU and fibrinolytic antigen levels in COVID-19 patients may be associated with disease severity and duration of hospitalization.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Clinical Neurology
Joachim C. Mertens, Vanessa Blanc-Guillemaud, Karen Claesen, Pere Cardona, Dirk Hendriks, Benoit Tyl, Carlos A. Molina
Summary: The study evaluated the kinetics of CPU during ischemic stroke treatment, revealing rapid activation and deactivation of the CPU system following thrombolysis and thrombectomy, indicating that a CPU inhibitor would need to be administered during rtPA infusion and in the hours that follow.
TRANSLATIONAL STROKE RESEARCH
(2022)
Article
Biochemical Research Methods
Jun X. Wheeler, Craig Thelwell, Peter Rigsby, Gail Whiting
Summary: In this study, a quantitative mass spectrometry method was established for measuring TAFI in human plasma. Traceability was achieved by using calibrators consisting of blank plasma spiked with a known amount of purified TAFI. This method enabled reliable and accurate measurement of TAFI concentration in plasma and demonstrated its applicability for assigning a common reference standard.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Chemistry, Medicinal
Arnaud-Pierre Schaffner, Patricia Sansilvestri-Morel, Nicole Despaux, Elisabeth Ruano, Thierry Persigand, Alain Rupin, Philippe Mennecier, Marie-Odile Vallez, Eric Raimbaud, Patrice Desos, Philippe Gloanec
Summary: Novel inhibitors targeting TAFIa designed in this paper show promising activity in thrombosis models, suggesting their potential for use in treating thrombotic diseases.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Erasmia Rouka, Sotirios G. Zarogiannis, Chrissi Hatzoglou, Konstantinos I. Gourgoulianis, Foteini Malli
Summary: This study focuses on the prediction and functional enrichment analysis of the TAFI interaction network and the microRNAs targeting the members of this network. It identifies the complement and coagulation cascades as well as neutrophil extracellular trap formation as pathways related to TAFI-related thrombosis and identifies important diseases such as cancer, stroke, and intracranial aneurysm associated with the identified microRNAs.
Article
Biochemistry & Molecular Biology
Karen Claesen, Joni De Loose, Pieter Van Wielendaele, Emilie De Bruyn, Yani Sim, Sofie Thys, Ingrid De Meester, Dirk Hendriks
Summary: Carboxypeptidase U (CPU) is synthesized in the liver as its inactive precursor proCPU and acts as a regulator of fibrinolysis and inflammation. Monocytes and macrophages, which play a central role in inflammation and thrombus formation, were found to express proCPU and secrete CPU. The expression and secretion of proCPU in these cells are related to their differentiation degree.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Karen Claesen, Joachim C. Mertens, Shahir Basir, Simon De Belder, Jeroen Maes, Johan Bosmans, Hilde Stoffelen, Ingrid De Meester, Dirk Hendriks
Summary: This pilot study aimed to explore the influence of statins on procarboxypeptidase U (proCPU) biology in patients with hypercholesterolemia. Findings showed that statin treatment led to a significant decrease in proCPU levels and improved fibrinolytic potential, particularly in patients with higher baseline proCPU levels.
CLINICAL THERAPEUTICS
(2021)
Article
Veterinary Sciences
Katherine E. Sotos, Robert Goggs, Alyssa P. Stablein, Marjory B. Brooks
Summary: This study compared fibrinolysis between dogs with sepsis and healthy controls. The results showed that dogs with sepsis had lower antithrombin activity, higher thrombin activatable fibrinolysis inhibitor activity, and higher concentrations of fibrinogen and D-dimer. Dogs with sepsis had increased coagulation and hemostatic potential, and decreased fibrinolysis potential. This study is important for understanding the pathophysiology of sepsis.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Hematology
Karen Claesen, Yani Sim, Shahir Basir, Simon De Belder, Tinne van den Keybus, Glenn Van Edom, Hilde Stoffelen, Gilles W. De Keulenaer, Johan Bosmans, Tijs Bringmans, Ingrid De Meester, Dirk Hendriks
Summary: This study confirms that plasma proCPU concentrations are increased in hyperlipidemic patients and can be reduced by atorvastatin treatment. The interindividual variation in proCPU concentrations is high in the hyperlipidemic cohort, with significantly higher levels compared to normolipidemic controls.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Thomas Vanassche, Rachel P. Rosovsky, Fares Moustafa, Harry R. Buller, Annelise Segers, Indu Patel, Minggao Shi, Naoki Miyoshi, Venkatesh Mani, Zahi Fayad, Dominique Stephan, Jeannot Schmidt, Michael A. Grosso, Victor F. Tapson, Peter Verhamme, M. Huisman
Summary: This study evaluated the tolerability and efficacy of adding DS-1040 in patients with intermediate-risk PE. The results showed that adding DS-1040 did not increase bleeding risk, but also did not improve thrombus resolution or right ventricular dilation.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2023)
Article
Medicine, Research & Experimental
Kanako Yoshida, Tetsuji Takabayashi, Yoshimasa Imoto, Masafumi Sakashita, Yukinori Kato, Norihiko Narita, Shigeharu Fujieda
Summary: This study found that serum TAFI levels significantly increased after SLIT treatment, showing a significant negative correlation with C3a levels, and inhibited mast cell degranulation and chemokine expression in fibroblasts.
Article
Clinical Neurology
Juan Marta-Enguita, Manuel Navarro-Oviedo, Roberto Munoz, Jorge Olier-Arenas, Guillermo Zalba, Ramon Lecumberri, Maite Mendioroz, Jose A. Paramo, Carmen Roncal, Josune Orbe
Summary: This study explores the presence of MMP-10 and TAFI in thrombi from ischemic stroke patients and their associations with clinical outcomes. The findings suggest that these hemostatic components in thrombus might influence response to thrombolytic treatment and patient outcomes. Further research is needed to explore the potential clinical impact of these findings on the development of new therapeutic strategies.
FRONTIERS IN NEUROLOGY
(2021)
Article
Hematology
Tessa Noordermeer, Jessica E. Molhoek, Roger E. G. Schutgens, Silvie A. E. Sebastian, Sandra Drost-Verhoef, Annet C. W. van Wesel, Philip G. de Groot, Joost C. M. Meijers, Rolf T. Urbanus
Summary: Anti-beta 2GPI and anti-prothrombin antibodies cause lupus anticoagulant (LA) through different mechanisms: anti-beta 2GPI antibodies interfere with FV activation by FXa through a direct interaction, while anti-prothrombin antibodies compete with FXa for phospholipid binding sites.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2021)
Article
Hematology
Laura Delvasto-Nunez, Dorina Roem, Kamran Bakhtiari, Gerard van Mierlo, Joost C. M. Meijers, Ilse Jongerius, Sacha S. Zeerleder
Summary: Hemolytic disorders involving intravascular hemolysis can lead to life-threatening thromboembolic complications, with hemolytic mediators such as red blood cell microvesicles stimulating coagulation activation through involvement of factors VIII and IX. Iron ions and phospholipids contribute to the procoagulant effect of hemolytic microvesicles, and oxidative stress plays a role in hypercoagulability.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Rheumatology
Daisy Vedder, Martijn Gerritsen, Joost C. M. Meijers, Michael T. Nurmohamed
Summary: This study aimed to investigate the coagulation system in gout patients and its association with disease activity. The results showed that patients with active gout had higher levels of thrombin generation markers, indicating a link between disease activity and coagulation. However, changes in disease activity after 1 year were not associated with significant changes in coagulation markers.
CLINICAL RHEUMATOLOGY
(2022)
Article
Hematology
Anja Maag, Nienke van Rein, Tim J. Schuijt, Wil F. Kopatz, Danielle Kruijswijk, Stella Thomassen, Tilman M. Hackeng, Rodney M. Camire, Tom van der Poll, Joost C. M. Meijers, Mettine H. A. Bos, Cornelis van't Veer
Summary: Plasma thrombin generation provides important information on coagulation status, but current parameters do not predict major bleeding in patients on anticoagulants. Activation of factor V by factor Xa contributes significantly to thrombin generation, with greater activation associated with increased risk of major bleeding during VKA therapy.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Marc V. A. van Moorsel, Geke C. Poolen, Cornelis A. Koekman, Sandra Verhoef, Steven de Maat, Arjan Barendrecht, Nadine D. van Kleef, Joost C. M. Meijers, Raymond M. Schiffelers, Coen Maas, Rolf T. Urbanus
Summary: We have developed a VhH anti-thrombomodulin (TM) clone 1 that inhibits TAFI activation and enhances tPA-mediated fibrinolysis under flow.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Correction
Rheumatology
Daisy Vedder, Martijn Gerritsen, Joost C. M. Meijers, Michael T. Nurmohamed
CLINICAL RHEUMATOLOGY
(2022)
Article
Hematology
Nicola J. Mutch, Sam Walters, Elizabeth E. Gardiner, Owen J. T. McCarty, Simon F. De Meyer, Verena Schroeder, Joost C. M. Meijers
Summary: Bleeding and thrombosis are major clinical problems. Basic research in this field is facing funding challenges. The International Society on Thrombosis and Haemostasis (ISTH) established a task force to identify research opportunities and priorities in this area.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Li Li, Mark Roest, Joost C. M. Meijers, Bas de Laat, Rolf T. Urbanus, Philip G. de Groot, Dana Huskens
Summary: Collagen activates platelets to initiate coagulation independently of certain clotting factors, and the activation of glycoprotein VI on platelets leads to the initiation of thrombin generation through platelet-derived FIXa activity.
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Awital Bar Barroeta, J. Arnoud Marquart, Joost C. M. Meijers
Summary: A reliable assay was established to measure the binding between FXI and thrombin, which is suitable for high-throughput screening. The assay produces a stable signal that meets the sensitivity and robustness criteria for application in high-throughput screening. Moreover, it was possible to measure modulation of the interaction with non-labelled FXI.
THROMBOSIS RESEARCH
(2022)
Article
Hematology
Awital Bar Barroeta, J. Arnoud Marquart, Kamran Bakhtiari, Alexander B. Meijer, Rolf T. Urbanus, Joost C. M. Meijers
Summary: Background Factor XI (FXI) is a potential target for novel anticoagulants, and nanobodies have been developed to interfere with FXIa mediated activation of factor IX (FIX), thereby reducing the risk of thrombosis.
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Martine J. Hollestelle, Joost C. M. Meijers, Piet Meijer
Summary: The study aimed to gain insight into the approach of laboratories toward VWD diagnosis. Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT were evaluated, and results were analyzed of a questionnaire that was sent to hemostasis laboratories about VWD diagnostic approaches.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2022)
Article
Hematology
Martine J. Hollestelle, Joost C. M. Meijers, Piet Meijer
Summary: The present study aimed to understand the approach of laboratories towards VWD diagnosis. Data from four samples of the external quality assessment (EQA) VWF surveys of the ECAT were evaluated, and the results of a questionnaire sent to hemostasis laboratories about VWD diagnostic approaches were analyzed.
SEMINARS IN THROMBOSIS AND HEMOSTASIS
(2022)
Letter
Hematology
Laure M. Fijen, Remy S. Petersen, Joost C. M. Meijers, Laura Bordone, Marcel Levi, Danny M. Cohn
THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Herm Jan M. Brinkman, Marleen Zuurveld, Joost C. M. Meijers
Summary: This study aimed to compare the efficacy of andexanet alfa and two different 4F-PCCs in reversing FXaI anticoagulation. The results showed that andexanet alfa effectively corrected thrombin generation parameters, while 4F-PCC predominantly increased peak thrombin and endogenous thrombin potential.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
Article
Hematology
Herm Jan M. Brinkman, Frauke Swieringa, Marleen Zuurveld, Alicia Veninga, Sanne L. N. Brouns, Johan W. M. Heemskerk, Joost C. M. Meijers
Summary: The study demonstrates the beneficial effect of combined use of PCC and FVC in reversing DOAC-induced coagulopathy by increasing thrombin generation, improving clot formation, enhancing clot strength and resistance to lysis.
RESEARCH AND PRACTICE IN THROMBOSIS AND HAEMOSTASIS
(2022)
