The influence of hydrogen ions on coagulation in traumatic brain injury, explored by molecular dynamics

Abstract

ABSTRACT 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.