Deciphering the coagulation profile through the dynamics of thrombin activity

Laat-Kremers, Romy de; Yan, Qiuting; Ninivaggi, Marisa; Maat, Moniek P.M. de; Laat, Bas de

doi:10.1038/s41598-020-69415-y

Cited by 21 publications

(36 citation statements)

References 43 publications

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“…The second study measured the complex formed between thrombin and A2M during thrombin generation measurement assessed with the CAT. 93 In these patients' thrombin-A2M complexes were significantly decreased compared to healthy controls, which is paralleled with the decreased overall thrombin generated. Whether and how A2M may worsen or not the bleeding risk in those patients is to the best of our knowledge unknown.…”

Section: Thrombotic Risk and Hemophiliamentioning

confidence: 76%

“…The authors hypothesized that this increase could be an overcompensation of the increased procoagulant state or may be due to an immune response because of transfused iso‐antigens. The second study measured the complex formed between thrombin and A2M during thrombin generation measurement assessed with the CAT 93 . In these patients’ thrombin–A2M complexes were significantly decreased compared to healthy controls, which is paralleled with the decreased overall thrombin generated.…”

Section: Alpha‐2‐macroglobulin In Hemostasismentioning

confidence: 99%

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Alpha‐2‐macroglobulin in hemostasis and thrombosis: An underestimated old double‐edged sword

Lagrange

Lecompte

Knopp

et al. 2022

Journal of Thrombosis and Haemostasis

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Many proteins have been conserved throughout evolution and display pleiotropic effects in several biological processes. This is certainly the case of alpha-2-macroglobulin (A2M), which is present in invertebrates and vertebrates and acts as an inhibitor of many proteinases. A2M is part of the alpha macroglobulin family, comprising six large glycoproteins.For more than half a century A2M has been reported to interact with several important proteinases involved in hemostasis.However, knowledge is limited concerning the role of A2M in hemostasis, thrombosis, and potential implications in human disorders.

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Section: Thrombotic Risk and Hemophiliamentioning

confidence: 76%

Section: Alpha‐2‐macroglobulin In Hemostasismentioning

confidence: 99%

Alpha‐2‐macroglobulin in hemostasis and thrombosis: An underestimated old double‐edged sword

Lagrange

Lecompte

Knopp

et al. 2022

Journal of Thrombosis and Haemostasis

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Section: Methodsmentioning

confidence: 99%

“…As AT levels are know to influence the course of prothrombin conversion indirectly, the individual prothrombin conversion curves were transformed to accommodate the effect of AT lowering 33 . We have shown previously that although the plasma AT level does not influence the total amount of prothrombin conversion (PC tot ), it does affect the maximal rate of prothrombin conversion (PC max ) dose-dependently 33 . To correct for this effect we fitted the relationship between plasma AT level and PC max in experimentally determined AT dose–response curves and transformed the prothrombin conversion curves obtained in the hemophilia A patients accordingly for each plasma level of AT.…”

Section: Methodsmentioning

confidence: 99%

Tailoring the effect of antithrombin-targeting therapy in haemophilia A using in silico thrombin generation

Laat-Kremers

Ninivaggi

Moort

et al. 2021

Sci Rep

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Factor (F) VIII deficiency causes bleeding in haemophilia A patients because of the reduced formation of procoagulant enzyme thrombin, which is needed to make the blood clot. We measured the dynamics of coagulation in haemophilia A patients by measuring thrombin generation (TG). Additionally, we quantified the procoagulant process of prothrombin conversion and anticoagulant process of thrombin inhibitor complex formation. In haemophilia A, prothrombin conversion is severely reduced, causing TG to be low. Nevertheless, the thrombin inactivation capacity of these patients is comparable to that in healthy subjects, leading to a severe imbalance between procoagulant and anticoagulant processes and a subsequent increased bleeding risk. A novel therapy in haemophilia A is the targeting of anticoagulant pathway, e.g. thrombin inhibitor antithrombin (AT), to restore the haemostatic balance. We simulated the effect of AT reduction on TG in silico. Lowering AT levels restored TG dose-dependently and an AT reduction of 90–95% led to almost normal TG in most patients . However, the variation in response to AT reduction was large between patients, indicating that this approach should be tailored to each individual patients. Ideally, TG and thrombin dynamics simulation could in the future contribute to the management of patients undergoing AT targeting therapy.

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“…Antithrombin inhibits approximately two-thirds of all thrombin formed, while α2M inactivates one-quarter of the formed thrombin 28 . The remaining thrombin is inhibited by a group of miscellaneous serpin and non-serpin inhibitors 29 . Figure 2.…”

Section: The Coagulation Cascadementioning

confidence: 99%

The dynamics of thrombin generation

Yan¹

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Deciphering the coagulation profile through the dynamics of thrombin activity

Abstract: measurements in plasma deficient in that specific factor and by performing correlation analysis in a group of healthy subjects (n = 122).

Cited by 21 publications

References 43 publications

Alpha‐2‐macroglobulin in hemostasis and thrombosis: An underestimated old double‐edged sword

Alpha‐2‐macroglobulin in hemostasis and thrombosis: An underestimated old double‐edged sword

Tailoring the effect of antithrombin-targeting therapy in haemophilia A using in silico thrombin generation

The dynamics of thrombin generation

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