The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics.
Carlos Romero DíazLaura Pérez Campos MayoralMaría Teresa Hernández HuertaAbraham Salvador Majluf-CruzStephanie Elizabeth Plascencia MoraEduardo Pérez-Campos MayoralGabriel Mayoral AndradeMargarito Martínez-CruzEdgar Zenteno-GalindoCarlos Alberto Matias-CervantesGabriela Vasquez-MartinezRuth Martínez CruzMiguel Ángel Reyes FrancoEli Cruz ParadaMaría Del Socorro Pina CansecoEduardo Pérez-Campos MayoralPublished in: Brain injury (2021)
Background: Patients in intensive care units with traumatic brain injuries (TBI) frequently present acid-base abnormalities and coagulability disorders, which complicate their condition.Objective: To identify protonation through in silico simulations of molecules involved in the process of coagulation in standard laboratory tests.Materials and methods: Ten patients with TBI were selected from the intensive care unit in addition to ten "healthy control subjects", and another nine patients as "disease control subjects"; the latter being a comparative group, corresponding to subjects with diabetes mellitus 2 (DM2). Fibrinogen, FVII, FVIII, FIX, FX, and D-dimer in the presence of acidification were evaluated in 20 healthy subjects in order to compare clinical results with molecular dynamics (MD), and to explain proton interactions and coagulation molecules.Results: The TBI group presented a slight, non-significant increase in D-dimer; but this was not present in "disease control subjects". Levels of fibrinogen, FVII, FIX, FX, and D-dimer were affected in the presence of acidification. We observed that various specific residues of coagulation factors "trap" ions.Conclusion: Protonation of tissue factor and factor VIIa may favor anticoagulant mechanisms, and protonation does not affect ligand binding sites of GPIIb/IIIa (PAC1) suggesting other causes for the low affinity to PAC1.
Keyphrases
- molecular dynamics
- traumatic brain injury
- end stage renal disease
- density functional theory
- ejection fraction
- newly diagnosed
- chronic kidney disease
- intensive care unit
- peritoneal dialysis
- prognostic factors
- atrial fibrillation
- type diabetes
- patient reported outcomes
- quantum dots
- white matter
- insulin resistance
- mass spectrometry
- metabolic syndrome
- venous thromboembolism
- skeletal muscle
- weight loss
- blood brain barrier
- subarachnoid hemorrhage
- mild traumatic brain injury
- water soluble
- aqueous solution