Blood Flow in Hemodialysis Catheters: A Numerical Simulation and Microscopic Analysis of In Vivo‐Formed Fibrin

Abstract

Although catheters with side holes allow high flow rate during hemodialysis, they also induce flow disturbances and create a critical hemodynamic environment that can favor fibrin deposition and thrombus formation. This study compared the blood flow and analyzed the influence of shear stress and shear rate in fibrin deposition and thrombus formation in nontunneled hemodialysis catheters with unobstructed side holes (unobstructed device) or with some side holes obstructed by blood thrombi (obstructed device). Computational fluid dynamics (CFD) was performed to simulate realistic blood flow under laminar and turbulent conditions. The results from the numerical simulations were compared with the fibrin distribution and thrombus architecture data obtained from scanning electron microscopy (SEM) and two photons laser scanning microscopy (TPLSM) on human thrombus formed in catheters removed from patients. CFD showed that regions of flow eddies and separation were mainly found in the venous holes region. TPLSM characterization of thrombi and fibrin structure in patient samples showed fibrin formations in accordance with simulated flux dynamics. Under laminar flow conditions, the wall shear stress close to border holes increased from 87.3±0.2 Pa in the unobstructed device to 176.2±0.5 Pa in the obstructed one. Under turbulent flow conditions, the shear stress increased by 47% when comparing the obstructed to the unobstructed catheter. The shear rates were generally higher than 5000/s and therefore sufficient to induce fibrin deposition. This findings were supported by SEM data documenting a preferential fibrin arrangement on side hole walls.

Microstructural evaluation by confocal and electron microscopy in thrombi developed in central venous catheters

“…This type of microscopy reaches a greater tissue depth when compared to Confocal Laser Scanning Microscopy, and the greater the tissue depth evaluated, the greater the red blood cell and white blood cell concentration, and the smaller the amount of fibrin interconnected to the cells (2) . In another study, a venous thrombus was observed by Two Photon Laser Scanning Microscopy in which the fibrin plate was surrounded by white blood cells close to the inner wall of the catheter opening (3) . This observation was also found in the present study while evaluating a thrombus using Confocal Laser Scanning Microscopy after 5 days of catheter permanence in the patient (Figures 3a and 3c).…”

“…Central venous catheters (CVCs) are radiopaque, and made of silicone, polyurethane or teflon. They may have one to three lumens arranged in parallel at the proximal end, and generally have lateral orifices at their distal end (1)(2)(3) . The openings may induce fibrin formation and subsequent thrombus development.…”

“…The openings may induce fibrin formation and subsequent thrombus development. Fibrin sheaths are composed of fibrinogen, albumin, lipoproteins, and coagulation factors that begin within 24 hours after catheter insertion (1)(2)(3)(4) . Fibrin is the first structural protein to form in thrombus composition and it may lead to catheter occlusion, extravasation of infused fluid, exchanging the catheter and loss of secondary access to thrombosis (5) .…”

“…Initial forming and maturing of the different thrombotic tissue components may lead to occlusion of the CVC lateral openings, mainly due to different conformations of the fibrin inside the opening and its adsorption to polymeric materials. Fibrin deposition on the catheter causes the surface to encapsulate, forming a sheath at the distal tip of the catheter (4)(5) .The process of protein adsorption to the polymer may become irreversible, and tissue dissolution becomes ineffective even by introducing fibrinolytic agents due to strong covalent bonds between plasma proteins and the catheter wall (2)(3) . The activation of a coagulation cascade increases the tendency for thrombus formation, which is an important cause of complications in patients using a venous catheter, which can not only lead to thrombosis near the vascular access, but also to emboli formation, deep venous thrombosis and the possible development of cardiac ischemia (8)(9)(10)(11)(12)(13)(14) .…”

“…Considering the three-dimensional microscopic architecture of a thrombus, Scanning Electron Microscopy (SEM) is one of the elective techniques for morphological characterization (13) . However, despite having high potential, SEM only provides information on superficial thrombus layers and their structural analysis (2)(3) . Integrating SEM and Confocal Laser Scanning Microscopy are promising for investigating thrombi in human samples, thus enabling better care performance in clinical practice and in the maintenance of CVCs, as they are evidence-based practices that respond to issues that arise daily.…”