Coagulopathy implications using a multiscale model of traumatic bleeding matching macro- and microcirculation

Abstract

Quantifying the relationship between vascular injury and the dynamic bleeding rate requires a multiscale model that accounts for changing and coupled hemodynamics between the global and microvascular levels. A lumped, global hemodynamic model of the human cardiovascular system with baroreflex control was coupled to a local 24-level bifurcating vascular network that spanned diameters from the muscular artery scale (0.1–1.3 mm) to capillaries (5–10 μm) via conservation of momentum and conservation of mass boundary conditions. For defined injuries of severing all vessels at each nth-level, the changing pressures and flowrates were calculated using prescribed shear-dependent hemostatic clot growth rates (normal or coagulopathic). Key results were as follows: 1) the upstream vascular network rapidly depressurizes to reduce blood loss; 2) wall shear rates at the hemorrhaging wound exit are sufficiently high (~10,000 s−1) to drive von Willebrand factor unfolding; 3) full coagulopathy results in >2-liter blood loss in 2 h for severing all vessels of 0.13- to 0.005-mm diameter within the bifurcating network, whereas full hemostasis limits blood loss to <100 ml within 2 min; and 4) hemodilution from transcapillary refill increases blood loss and could be implicated in trauma-induced coagulopathy. A sensitivity analysis on length-to-diameter ratio and branching exponent demonstrated that bleeding was strongly dependent on these tissue-dependent network parameters. This is the first bleeding model that prescribes the geometry of the injury to calculate the rate of pressure-driven blood loss and local wall shear rate in the presence or absence of coagulopathic blood. NEW & NOTEWORTHY We developed a multiscale model that couples a lumped, global hemodynamic model of a patient to resolved, single-vessel wounds ranging from the small artery to capillary scale. The model is able to quantify wall shear rates, seal rates, and blood loss rates in the presence and absence of baroreflex control and hemodilution.

A three-dimensional multiscale model for the prediction of thrombus growth under flow with single-platelet resolution

“…The framework presented here may be further extended and employed in models for traumatic bleeding based on platelets from trauma patients [38]. In prior work, a lumped model of the cardiovascular system was coupled to a bleeding branching vasculature network model to predict the bleeding trajectory of a patient in response to defined injuries of severing blood vessels [39]. However, a coarse-grained hemostasis model that used a parametrized wound seal rate as a function of the shear rate was used in the study [40].…”

Intravenous Hemostats: Foundation, Targeting, and Controlled-Release

“…The shear rate and elongational flow in wounds ranged from 50 to 410 μm using three models of vascular puncture or transection: (A) the shear rate calculated for different scenarios; (B) the maximum shear rate at the edge of wounds ranges from 50 to 410 μm after puncture of the cubital vein, saphenous vein, aorta, or carotid artery in mice; (C) the maximum elongational flow at the edge of wounds (edge) and the mean values in a broad area in front of wounds (front); (D) the relationship between the maximum shear rate and injury radius using the hybrid computational models. Reproduced with permission from ref . Copyright 2022 Elsevier.…”

Predicting risk for trauma patients using static and dynamic information from the MIMIC III database

“…There have also been physics-based models constructed to model trauma. Ursino et al, developed a system of ordinary differential equations to describe the circulatory system as a closed loop with feedback, which has been extended to simulate traumatic bleeding [ 5 , 14 ]. While able to simulate blood loss patterns, these types of models are difficult to connect a specific injury to an outcome [ 4 , 15 – 17 ].…”

“…Ursino et al, developed a system of ordinary differential equations to describe the circulatory system as a closed loop with feedback, which has been extended to simulate traumatic bleeding [ 5 , 14 ]. While able to simulate blood loss patterns, these types of models are difficult to connect a specific injury to an outcome [ 4 , 15 – 17 ]. Hirshberg et al, also developed a model to evaluate the impact of the transfusion of blood products on dilutional coagulopathy and found that resuscitation with more than 5 units of red blood cells would lead to coagulopathy [ 18 ].…”