Systems Biology Approach for Personalized Hemostasis Correction

Abstract

The correction of blood coagulation impairments of a bleeding or thrombotic nature employs standard protocols where the type of drug, its dose and the administration regime are stated. However, for a group of patients, such an approach may be ineffective, and personalized therapy adjustment is needed. Laboratory hemostasis tests are used to control the efficacy of therapy, which is expensive and time-consuming. Computer simulations may become an inexpensive and fast alternative to real blood tests. In this work, we propose a procedure to numerically define the individual hemostasis profile of a patient and estimate the anticoagulant efficacy of low-molecular-weight heparin (LMWH) based on the computer simulation of global hemostasis assays. We enrolled a group of 12 patients receiving LMWH therapy and performed routine coagulation assays (activated partial thromboplastin time and prothrombin time) and global hemostasis assays (thrombodynamics and thrombodynamics-4d) and measured anti-Xa activity, fibrinogen, prothrombin and antithrombin levels, creatinine clearance, lipid profiles and clinical blood counts. Blood samples were acquired 3, 6 and 12 h after LMWH administration. We developed a personalized pharmacokinetic model of LMWH and coupled it with the mechanism-driven blood coagulation model, which described the spatial dynamics of fibrin and thrombin propagation. We found that LMWH clearance was significantly lower in the group with high total cholesterol levels. We generated an individual patient’s hemostasis profile based on the results of routine coagulation assays. We propose a method to simulate the results of global hemostasis assays in the case of an individual response to LMWH therapy, which can potentially help with hemostasis corrections based on the output of global tests.