Acoustic determination of early stages of intravascular blood coagulation. Philosophical transactions of the royal society

The blood coagulation system (BCS) is a complex biological system playing a principal role in the maintenance of haemostasis. Insufficient activity of the BCS may lead to bleeding and blood loss (e.g. in the case of haemophilia). On the other hand, excessive activity may cause intravascular blood coagulation, thromboses and embolization. Most of the methods currently used for BCS monitoring suffer from the major disadvantage of being invasive. The purpose of the present work is to demonstrate the feasibility of using ultrasonic methods for noninvasive registration of the early stages of blood coagulation processes in intensive flows. With this purpose, a special experimental set-up was designed, facilitating the simultaneous detection of optical and acoustic signals during the clotting process. It was shown that (i) as microemboli appear in the flow during the early stage of blood coagulation, the intensity of the Doppler signal increases twofold, and (ii) microemboli formation in the early stages of blood clotting always reveals itself through an acoustic contrast. Both of these effects are well defined, so we hope that they may be used for non-invasive BCS monitoring in clinical practice

Control of fibrinolytic drug injection via real-time ultrasonic monitoring of blood coagulation.

In the present study, we investigated the capabilities of a novel ultrasonic approach for real-time control of fibrinolysis under flow conditions. Ultrasonic monitoring was performed in a specially designed experimental in vitro system. Fibrinolytic agents were automatically injected at ultrasonically determined stages of the blood clotting. The following clots dissolution in the system was investigated by means of ultrasonic monitoring. It was shown, that clots resistance to fibrinolysis significantly increases during the first 5 minutes since the formation of primary micro-clots. The efficiency of clot lysis strongly depends on the concentration of the fibrinolytic agent as well as the delay of its injection moment. The ultrasonic method was able to detect the coagulation at early stages, when timely pharmacological intervention can still prevent the formation of macroscopic clots in the experimental system. This result serves as evidence that ultrasonic methods may provide new opportunities for real-time monitoring and the early pharmacological correction of thrombotic complications in clinical practice

Platelet activation via dynamic conformational changes of von Willebrand factor under shear.

Shear-induced conformational changes of von Willebrand factor (VWF) play an important role in platelet activation. A novel approach describing VWF unfolding on the platelet surface under dynamic shear stress is proposed. Cumulative effect of dynamic shear on platelet activation via conformational changes of VWF is analysed. The critical condition of shear-induced platelet activation is formulated. The explicit expression for the threshold value of cumulative shear stress as a function of VWF multimer size is derived. The results open novel prospects for pharmacological regulation of shear-induced platelet activation through control of VWF multimers size distribution

Successive stages of a solid thrombus formation.

<p>a—thrombus nucleation, b—formation of fibre-like fibrin structure, c—fibre-like structure thickening, d—solid thrombus. Shown are the color maps of <i>N</i>_<i>w</i>—the weight-average number of monomers in fibrin-polymer in the vessel, with red areas representing regions of fibrin gel formation (</p><p></p><p></p><p></p><p><mi>N</mi><mi>w</mi></p><mo>≥</mo><p><mi>N</mi><mi>w</mi><mi>s</mi></p><p></p><p></p><p></p>). Streamlines are plotted to visualize the flow, and the separatrix, which divides the core of the flow from the recirculation zone, is shown with a dashed line. Parameters used in the simulations are: <i>Re</i> = 130, <i>h</i> = 0.5, <p></p><p></p><p></p><p><mi>d</mi><mo>~</mo></p><mo>=</mo><mn>0</mn><mo>.</mo><mn>5</mn><p></p><p></p><p></p>, <p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><mn>2</mn><p></p><mo>=</mo><mn>9</mn><mo>.</mo><mn>5</mn><p></p><p></p><p></p>. Note that only a fragment of the vessel closest to the plaque is depicted.<p></p

Parametric diagram of blood coagulation system regimes in the (Re,μ~2) parameter space.

<p><i>Re</i> is the Reynolds number and </p><p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><mn>2</mn><p></p><p></p><p></p><p></p> is the non-dimensional vessel wall permeability. Label “I” is used to denote stationary regimes with no coagulation in the vessel while “II” marks the regimes with thrombi formation. Also shown are two typical values <i>Re</i>₁, <i>Re</i>₂ marking the boundary of the coagulation regime for a given <p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><mn>2</mn><p></p><p></p><p></p><p></p> and <p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><p><mi>m</mi><mi>i</mi><mi>n</mi></p><p></p><p></p><p></p><p></p>—the permeability of the vessel wall below which clotting does not occur under any hydrodynamic conditions. Finally, <i>Re</i> = <i>Re</i>_<i>τ</i>2 indicates the lowest Reynolds number at which the shear stress reaches <i>τ</i>₂ and the local permeability of the vessel reaches <p></p><p></p><p></p><p></p><p><mi>μ</mi><mn>2</mn></p><mo>~</mo><p></p><p></p><p></p><p></p>. <i>h</i> = 0.6, <i>d</i> = 0.4.<p></p

Geometry of the vessel fragment.

<p><i>L</i>_<i>x</i>, <i>L</i>_<i>y</i> and <i>H</i> correspond to vessel length, cross section diameter and plaque height. Γ_<i>in</i> and Γ_<i>out</i> denote inlet and outlet boundaries respectively. Γ₊ and Γ₋ refer to upper and lower vessel walls respectively.</p

Parameter values.

<p>Parameter values.</p

Successive stages of a friable floating fibrin structure formation.

<p>a—thrombus nucleation, b—formation of fibre-like fibrin structure, c—thick and friable floating fibrin structure. Shown are the color maps of <i>N</i>_<i>w</i>—the weight-average number of monomers in fibrin-polymer in the vessel, with red areas representing regions of fibrin gel formation (</p><p></p><p></p><p></p><p><mi>N</mi><mi>w</mi></p><mo>≥</mo><p><mi>N</mi><mi>w</mi><mi>s</mi></p><p></p><p></p><p></p>). Streamlines are plotted to visualize the flow, and the separatrix is shown with a dashed line. Parameters used in these simulations are: <i>Re</i> = 180, <i>h</i> = 0.6, <p></p><p></p><p></p><p><mi>d</mi><mo>~</mo></p><mo>=</mo><mn>0</mn><mo>.</mo><mn>4</mn><p></p><p></p><p></p>, <p></p><p></p><p></p><p><mi>d</mi><mo>~</mo></p><mo>=</mo><mn>12</mn><p></p><p></p><p></p>. Note that only a fragment of the vessel closest to the plaque is depicted.<p></p

Parametric diagrams of blood coagulation regimes in the (<i>h</i>, <i>Re</i>) parameter space for two different values of d~, the non-dimensional plaque diameter.

<p>Region “I” denotes regimes in which there is no coagulation, region “II” represents regimes of macroscopic thrombus formation. (a): </p><p></p><p></p><p></p><p><mi>d</mi><mo>~</mo></p><mo>=</mo><mn>0</mn><mo>.</mo><mn>3</mn><p></p><p></p><p></p>, <p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><mn>2</mn><p></p><mo>=</mo><mn>7</mn><p></p><p></p><p></p>; (b): <p></p><p></p><p></p><p><mi>d</mi><mo>~</mo></p><mo>=</mo><mn>0</mn><mo>.</mo><mn>5</mn><p></p><p></p><p></p>, <p></p><p></p><p></p><p></p><p><mi>μ</mi><mo>~</mo></p><mn>2</mn><p></p><mo>=</mo><mn>7</mn><p></p><p></p><p></p>.<p></p

Flow rate waveforms.

(PDF)</p