open access
In seeking diagnostic tool for laboratory monitoring of FXII-targeting agents, could assessment of rotational thromboelastometry (ROTEM) in patients with factor XII deficiency be useful?
, 3, 3
Affiliations- Department of Haematology, Copernicus Memorial Hospital in Lodz, Łódź, Poland
- Department of Haematooncology, Copernicus Memorial Hospital in Lodz, Łódź, Poland
- Department of Haemostasis Disorders, Medical University of Lodz, Łódź, Poland
open access
Abstract
Introduction: Targeting factor XII (FXII) is a new concept for safe thrombosis prophylaxis. Global hemostasis tests offer promise in terms of the laboratory monitoring of FXII inhibition. The present study examines selected parameters of rotational thromboelastometry (ROTEM) in patients with FXII deficiency.
The objective of this study was to assess the impact of FXII deficiency on selected parameters of ROTEM, which can be significant in the laboratory monitoring of FXII inhibition.
Material and methods: The study included 20 patients with FXII deficiency ≤40% and 21 volunteers free of it. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF), and maximum lysis (ML) were recorded in ROTEM.
Results: For the INTEM test, CT and CFT readings were markedly higher in FXII deficient patients than in controls. No marked differences in relation to MCF and ML were found.
Conclusion: The results of ROTEM show that FXII deficiency has a great impact on the initiation and amplification of coagulation. This was confirmed by a number of marked correlations between FXII activity and certain ROTEM parameters. ROTEM tests merit further investigation as treatment control strategies in the context of FXII inhibition.
Abstract
Introduction: Targeting factor XII (FXII) is a new concept for safe thrombosis prophylaxis. Global hemostasis tests offer promise in terms of the laboratory monitoring of FXII inhibition. The present study examines selected parameters of rotational thromboelastometry (ROTEM) in patients with FXII deficiency.
The objective of this study was to assess the impact of FXII deficiency on selected parameters of ROTEM, which can be significant in the laboratory monitoring of FXII inhibition.
Material and methods: The study included 20 patients with FXII deficiency ≤40% and 21 volunteers free of it. Clotting time (CT), clot formation time (CFT), alpha angle (α), maximum clot firmness (MCF), and maximum lysis (ML) were recorded in ROTEM.
Results: For the INTEM test, CT and CFT readings were markedly higher in FXII deficient patients than in controls. No marked differences in relation to MCF and ML were found.
Conclusion: The results of ROTEM show that FXII deficiency has a great impact on the initiation and amplification of coagulation. This was confirmed by a number of marked correlations between FXII activity and certain ROTEM parameters. ROTEM tests merit further investigation as treatment control strategies in the context of FXII inhibition.
Keywords
factor XII deficiency, ROTEM, FXII as a target for thrombosis prevention, laboratory monitoring of FXII inhibition
About this articleTitle
In seeking diagnostic tool for laboratory monitoring of FXII-targeting agents, could assessment of rotational thromboelastometry (ROTEM) in patients with factor XII deficiency be useful?
Journal
Issue
Article type
Original research article
Pages
267-272
Published online
2022-08-04
Page views
3461
Article views/downloads
216
DOI
Bibliographic record
Acta Haematol Pol 2022;53(4):267-272.
Keywords
factor XII deficiency
ROTEM
FXII as a target for thrombosis prevention
laboratory monitoring of FXII inhibition
Authors
Paulina Stelmach
Weronika Nowak
Marta Robak
Emilia Krzemińska
Marzena Tybura-Sawicka
Krzysztof Chojnowski
Jacek Treliński
References (30)- Maas C, Renné T. Coagulation factor XII in thrombosis and inflammation. Blood. 2018; 131(17): 1903–1909.
- Kohs TCL, Lorentz CU, Johnson J, et al. Development of coagulation factor XII antibodies for inhibiting vascular device-related thrombosis. Cell Mol Bioeng. 2021; 14(2): 161–175.
- Kalinin DV. Factor XII(a) inhibitors: a review of the patent literature. Expert Opin Ther Pat. 2021; 31(12): 1155–1176.
- Colman RW, Schmaier AH. Contact system: a vascular biology modulator with anticoagulant, profibrinolytic, antiadhesive, and proinflammatory attributes. Blood. 1997; 90(10): 3819–3843.
- Stavrou E, Schmaier AH. Factor XII: what does it contribute to our understanding of the physiology and pathophysiology of hemostasis & thrombosis. Thromb Res. 2010; 125(3): 210–215.
- Schmaier AH, Stavrou EX. Factor XII — what's important but not commonly thought about. Res Pract Thromb Haemost. 2019; 3(4): 599–606.
- Larsson M, Rayzman V, Nolte MW, et al. A factor XIIa inhibitory antibody provides thromboprotection in extracorporeal circulation without increasing bleeding risk. Sci Transl Med. 2014; 6(222): 222ra17.
- Kenne E, Nickel KF, Long AT, et al. Factor XII: a novel target for safe prevention of thrombosis and inflammation. J Intern Med. 2015; 278(6): 571–585.
- Weitz JI, Fredenburgh JC. Factors XI and XII as targets for new anticoagulants. Front Med (Lausanne). 2017; 4: 19.
- Wilbs J, Kong XD, Middendorp SJ, et al. Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs. Nat Commun. 2020; 11(1): 3890.
- Tripodi A, Chantarangkul V, Mannucci PM. Acquired coagulation disorders: revisited using global coagulation/anticoagulation testing. Br J Haematol. 2009; 147(1): 77–82.
- Mann KG. Thrombin formation. Chest. 2003; 124(3 Suppl): 4S–410S.
- Dahlbäck B. Progress in the understanding of the protein C anticoagulant pathway. Int J Hematol. 2004; 79(2): 109–116.
- Whiting D, DiNardo JA. TEG and ROTEM: technology and clinical applications. Am J Hematol. 2014; 89(2): 228–232.
- Akay OM. The double hazard of bleeding and thrombosis in hemostasis from a clinical point of view: a global assessment by rotational thromboelastometry (ROTEM). Clin Appl Thromb Hemost. 2018; 24(6): 850–858.
- Young G, Sørensen B, Dargaud Y, et al. Thrombin generation and whole blood viscoelastic assays in the management of hemophilia: current state of art and future perspectives. Blood. 2013; 121(11): 1944–1950.
- Luddington RJ. Thrombelastography/thromboelastometry. Clin Lab Haematol. 2005; 27(2): 81–90.
- Lang T, Bauters A, Braun SL, et al. Multi-centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagul Fibrinolysis. 2005; 16(4): 301–310.
- Lang T, von Depka M. [Possibilities and limitations of thrombelastometry/-graphy] [Article in German]. Hamostaseologie. 2006; 26(3 Suppl 1): S20–S29.
- Treliński J, Misiewicz M, Robak M, et al. Assessment of rotation thromboelastometry (ROTEM) parameters in patients with multiple myeloma at diagnosis. Thromb Res. 2014; 133(4): 667–670.
- Crochemore T, Piza FM, Rodrigues RD, et al. A new era of thromboelastometry. Einstein (Sao Paulo). 2017; 15(3): 380–385.
- Govers-Riemslag JWP, Konings J, Cosemans JM, et al. Impact of deficiency of intrinsic coagulation factors XI and XII on ex vivo thrombus formation and clot lysis. TH Open. 2019; 3(3): e273–e285.
- Konings J, Govers-Riemslag JWP, Philippou H, et al. Factor XIIa regulates the structure of the fibrin clot independently of thrombin generation through direct interaction with fibrin. Blood. 2011; 118(14): 3942–3951.
- Konings J, Hoving LR, Ariëns RS, et al. The role of activated coagulation factor XII in overall clot stability and fibrinolysis. Thromb Res. 2015; 136(2): 474–480.
- Levi M, Hack CE, de Boer JP, et al. Reduction of contact activation related fibrinolytic activity in factor XII deficient patients. Further evidence for the role of the contact system in fibrinolysis in vivo. J Clin Invest. 1991; 88(4): 1155–1160.
- Goldsmith GH, Saito H, Ratnoff OS. The activation of plasminogen by Hageman factor (Factor XII) and Hageman factor fragments. J Clin Invest. 1978; 62(1): 54–60.
- Hemker HC, Giesen PL, Ramjee M, et al. The thrombogram: monitoring thrombin generation in platelet-rich plasma. Thromb Haemost. 2000; 83(4): 589–591.
- Longstaff C. Measuring fibrinolysis: from research to routine diagnostic assays. J Thromb Haemost. 2018; 16(4): 652–662.
- Kuiper GJ, Kleinegris MCF, van Oerle R, et al. Validation of a modified thromboelastometry approach to detect changes in fibrinolytic activity. Thromb J. 2016; 14: 1.
- Kluft C, Dooijewaard G, Emeis JJ. Role of the contact system in fibrinolysis. Semin Thromb Hemost. 1987; 13(1): 50–68.