Thrombin generation: a global coagulation procedure to investigate hypo- and hyper-coagulability

Tripodi, Armando

doi:10.3324/haematol.2020.253047

Cited by 12 publications

(7 citation statements)

References 20 publications

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“…Our model predictions were in good agreement with the reported experimental findings in the literature. Indeed, it was shown experimentally that elevated ETP and peak concentrations values were associated with hypercoagulable states [42], while an increased time to peak was associated with poor coagulation [43,44]. It was also shown that the lag time has a minimal effect on coagulation, which also agrees with our model findings.…”

Section: Discussionsupporting

confidence: 90%

Thrombin Generation Thresholds for Coagulation Initiation under Flow

Bouchnita,

Yadav,

Llored

et al. 2023

Axioms

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In veins, clotting initiation displays a threshold response to flow intensity and injury size. Mathematical models can provide insights into the conditions leading to clot growth initiation under flow for specific subjects. However, it is hard to determine the thrombin generation curves that favor coagulation initiation in a fast manner, especially when considering a wide range of conditions related to flow and injury size. In this work, we propose to address this challenge by using a neural network model trained with the numerical simulations of a validated 2D model for clot formation. Our surrogate model approximates the results of the 2D simulations, reaching an accuracy of 94% on the test dataset. We used the trained artificial neural network to determine the threshold for thrombin generation parameters that alter the coagulation initiation response under varying flow speed and injury size conditions. Our model predictions show that increased levels of the endogenous thrombin potential (ETP) and peak thrombin concentration increase the likelihood of coagulation initiation, while an elevated time to peak decreases coagulation. The lag time has a small effect on coagulation initiation, especially when the injury size is small. Our surrogate model can be considered as a proof-of-concept of a tool that can be deployed to estimate the risk of bleeding in specific patients based on their Thrombin Generation Assay results.

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Section: Discussionsupporting

confidence: 90%

Thrombin Generation Thresholds for Coagulation Initiation under Flow

Bouchnita,

Yadav,

Llored

et al. 2023

Axioms

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“…Our results related to most thrombin generation parameters confirm this statement, except for the ETP performed using low tissue factor (TF), which emerged as an important tool to evaluate the bleeding potential of hemophilia A patients. The area under the curve, known as ETP, represents the net amount of thrombin generation, reflecting the balance between procoagulant and anticoagulant forces [19], being the parameter that most correlates with clinical findings. LBP patients showed a higher ETP value compared with those with BPH, which means a larger area under the curve, that is, less inhibition of the thrombin formed by the natural anticoagulation mechanism.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic variation in severe hemophilia A is related to endogenous thrombin potential and plasma levels of factor VII

Chaves

Fonseca

Araújo

et al. 2022

Blood Coagulation &Amp; Fibrinolysis

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Hemophilia A is a bleeding disorder caused by deficiency or low activity of circulating factor VIII characterized by prolonged blood coagulation time and often spontaneous bleeding. Patients with the severe form of the disease may present considerable heterogeneity in the occurrence of bleeding episodes and some of them have a mild hemophilia A phenotype. This study aimed to evaluate the association of biomarkers and coagulation parameters to the differential hemorrhagic profile of severe hemophilia A patients. Polymorphisms in the genes of proteins C and S, factors V and VII and prothrombin were evaluated in a group of severe hemophilia A patients with a broad spectrum of bleeding profile. Plasma levels of coagulation factors and thrombin generation were also analyzed. This study included 59 Brazilian hemophilia A patients who were allocated into low bleeding profile (LBP; n = 33) and high bleeding profile (HBP; n = 26) groups based on their joint and muscle bleeding episodes requiring treatment in the 5 years before inclusion in the study. Results evidenced that endogenous thrombin potential (ETP) and plasma factor VII levels were significantly higher in the LBP group. Results indicate a prominent importance of FVII plasma activity and endogenous thrombin potential on the differential bleeding phenotype of hemophilia A patients.

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“…A (nanomolar) and endogenous thrombin potential (nanomolar per minute) were recorded (Tripodi, 2020). Owing to the reduced amount of platelet-poor plasma available (because of the very high haematocrits), the thrombin generation assay was not performed in 2 of 15 (13%) EE− and 13 of 30 (43%) EE+, and not performed in 1 of 10 (10%) LL, owing to technical failure.…”

Section: Thrombin Generationmentioning

confidence: 99%

Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

Champigneulle,

Caton,

Seyve

et al. 2024

Experimental Physiology

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Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE−). Blood samples were collected from 30 EE+ and 15 EE− in La Rinconada (Peru, 5100–5300 m a.s.l.), with special attention given to the sampling pre‐analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet‐poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE− and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

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Thrombin generation: a global coagulation procedure to investigate hypo- and hyper-coagulability

Cited by 12 publications

References 20 publications

Thrombin Generation Thresholds for Coagulation Initiation under Flow

Thrombin Generation Thresholds for Coagulation Initiation under Flow

Phenotypic variation in severe hemophilia A is related to endogenous thrombin potential and plasma levels of factor VII

Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?

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