Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review

In the pursuit of personalized medicine, there is a growing demand for computational models with parameters that are easily obtainable to accelerate the development of potential solutions. Blood tests, owing to their affordability, accessibility, and routine use in healthcare, offer valuable biomark...

Full description

Saved in:
Bibliographic Details
Main Authors: Mohamad Al Bannoud, Tiago Dias Martins, Silmara Aparecida de Lima Montalvão, Joyce Maria Annichino-Bizzacchi, Rubens Maciel Filho, Maria Regina Wolf Maciel
Format: Article
Language:English
Published: AIMS Press 2024-12-01
Series:Mathematical Biosciences and Engineering
Subjects:
Online Access:https://www.aimspress.com/article/doi/10.3934/mbe.2024339
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832591014859112448
author Mohamad Al Bannoud
Tiago Dias Martins
Silmara Aparecida de Lima Montalvão
Joyce Maria Annichino-Bizzacchi
Rubens Maciel Filho
Maria Regina Wolf Maciel
author_facet Mohamad Al Bannoud
Tiago Dias Martins
Silmara Aparecida de Lima Montalvão
Joyce Maria Annichino-Bizzacchi
Rubens Maciel Filho
Maria Regina Wolf Maciel
author_sort Mohamad Al Bannoud
collection DOAJ
description In the pursuit of personalized medicine, there is a growing demand for computational models with parameters that are easily obtainable to accelerate the development of potential solutions. Blood tests, owing to their affordability, accessibility, and routine use in healthcare, offer valuable biomarkers for assessing hemostatic balance in thrombotic and bleeding disorders. Incorporating these biomarkers into computational models of blood coagulation is crucial for creating patient-specific models, which allow for the analysis of the influence of these biomarkers on clot formation. This systematic review aims to examine how clinically relevant biomarkers are integrated into computational models of blood clot formation, thereby advancing discussions on integration methodologies, identifying current gaps, and recommending future research directions. A systematic review was conducted following the PRISMA protocol, focusing on ten clinically significant biomarkers associated with hemostatic disorders: D-dimer, fibrinogen, Von Willebrand factor, factor Ⅷ, P-selectin, prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin Ⅲ, protein C, and protein S. By utilizing this set of biomarkers, this review underscores their integration into computational models and emphasizes their integration in the context of venous thromboembolism and hemophilia. Eligibility criteria included mathematical models of thrombin generation, blood clotting, or fibrin formation under flow, incorporating at least one of these biomarkers. A total of 53 articles were included in this review. Results indicate that commonly used biomarkers such as D-dimer, PT, and APTT are rarely and superficially integrated into computational blood coagulation models. Additionally, the kinetic parameters governing the dynamics of blood clot formation demonstrated significant variability across studies, with discrepancies of up to 1, 000-fold. This review highlights a critical gap in the availability of computational models based on phenomenological or first-principles approaches that effectively incorporate affordable and routinely used clinical test results for predicting blood coagulation. This hinders the development of practical tools for clinical application, as current mathematical models often fail to consider precise, patient-specific values. This limitation is especially pronounced in patients with conditions such as hemophilia, protein C and S deficiencies, or antithrombin deficiency. Addressing these challenges by developing patient-specific models that account for kinetic variability is crucial for advancing personalized medicine in the field of hemostasis.
format Article
id doaj-art-2155afa32ee7412ea18d35e24d121b46
institution Kabale University
issn 1551-0018
language English
publishDate 2024-12-01
publisher AIMS Press
record_format Article
series Mathematical Biosciences and Engineering
spelling doaj-art-2155afa32ee7412ea18d35e24d121b462025-01-23T05:05:30ZengAIMS PressMathematical Biosciences and Engineering1551-00182024-12-0121127707773910.3934/mbe.2024339Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic reviewMohamad Al Bannoud0Tiago Dias Martins1Silmara Aparecida de Lima Montalvão2Joyce Maria Annichino-Bizzacchi3Rubens Maciel Filho4Maria Regina Wolf Maciel5Laboratory of Optimization, Design, and Advanced Control, School of Chemical Engineering, Universidade Estadual de Campinas, Campinas, São Paulo, BrazilDepartamento de Engenharia Química, Universidade Federal de São Paulo, Diadema, São Paulo, BrazilHematology and Hemotherapy Center, Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade Estadual de Campinas, Campinas, São Paulo, BrazilHematology and Hemotherapy Center, Instituto Nacional de Ciência e Tecnologia do Sangue, Universidade Estadual de Campinas, Campinas, São Paulo, BrazilLaboratory of Optimization, Design, and Advanced Control, School of Chemical Engineering, Universidade Estadual de Campinas, Campinas, São Paulo, BrazilLaboratory of Optimization, Design, and Advanced Control, School of Chemical Engineering, Universidade Estadual de Campinas, Campinas, São Paulo, BrazilIn the pursuit of personalized medicine, there is a growing demand for computational models with parameters that are easily obtainable to accelerate the development of potential solutions. Blood tests, owing to their affordability, accessibility, and routine use in healthcare, offer valuable biomarkers for assessing hemostatic balance in thrombotic and bleeding disorders. Incorporating these biomarkers into computational models of blood coagulation is crucial for creating patient-specific models, which allow for the analysis of the influence of these biomarkers on clot formation. This systematic review aims to examine how clinically relevant biomarkers are integrated into computational models of blood clot formation, thereby advancing discussions on integration methodologies, identifying current gaps, and recommending future research directions. A systematic review was conducted following the PRISMA protocol, focusing on ten clinically significant biomarkers associated with hemostatic disorders: D-dimer, fibrinogen, Von Willebrand factor, factor Ⅷ, P-selectin, prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin Ⅲ, protein C, and protein S. By utilizing this set of biomarkers, this review underscores their integration into computational models and emphasizes their integration in the context of venous thromboembolism and hemophilia. Eligibility criteria included mathematical models of thrombin generation, blood clotting, or fibrin formation under flow, incorporating at least one of these biomarkers. A total of 53 articles were included in this review. Results indicate that commonly used biomarkers such as D-dimer, PT, and APTT are rarely and superficially integrated into computational blood coagulation models. Additionally, the kinetic parameters governing the dynamics of blood clot formation demonstrated significant variability across studies, with discrepancies of up to 1, 000-fold. This review highlights a critical gap in the availability of computational models based on phenomenological or first-principles approaches that effectively incorporate affordable and routinely used clinical test results for predicting blood coagulation. This hinders the development of practical tools for clinical application, as current mathematical models often fail to consider precise, patient-specific values. This limitation is especially pronounced in patients with conditions such as hemophilia, protein C and S deficiencies, or antithrombin deficiency. Addressing these challenges by developing patient-specific models that account for kinetic variability is crucial for advancing personalized medicine in the field of hemostasis.https://www.aimspress.com/article/doi/10.3934/mbe.2024339mathematical modelingpersonalized medicinethrombosishemostasiscomputational modelbiomarkers.
spellingShingle Mohamad Al Bannoud
Tiago Dias Martins
Silmara Aparecida de Lima Montalvão
Joyce Maria Annichino-Bizzacchi
Rubens Maciel Filho
Maria Regina Wolf Maciel
Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
Mathematical Biosciences and Engineering
mathematical modeling
personalized medicine
thrombosis
hemostasis
computational model
biomarkers.
title Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
title_full Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
title_fullStr Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
title_full_unstemmed Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
title_short Integrating biomarkers for hemostatic disorders into computational models of blood clot formation: A systematic review
title_sort integrating biomarkers for hemostatic disorders into computational models of blood clot formation a systematic review
topic mathematical modeling
personalized medicine
thrombosis
hemostasis
computational model
biomarkers.
url https://www.aimspress.com/article/doi/10.3934/mbe.2024339
work_keys_str_mv AT mohamadalbannoud integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview
AT tiagodiasmartins integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview
AT silmaraaparecidadelimamontalvao integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview
AT joycemariaannichinobizzacchi integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview
AT rubensmacielfilho integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview
AT mariareginawolfmaciel integratingbiomarkersforhemostaticdisordersintocomputationalmodelsofbloodclotformationasystematicreview