In 1897, Brodie and Russell1 published their article describing what was one of the first devices, other than a simple capillary tube, for testing blood coagulation. The contraption consisted of a small glass chamber put under a microscope that allowed small puffs of air to be blown at a drop of blood. With blood in liquid form, the force from the air caused the cells to move around the glass sheet. As coagulation progressed, the puff of air would then cause the forming clot to slightly indent and then spring back into place, thus demonstrating the elastic properties of clot. The endpoint of the test was the time it took for the blood to become immobile. However, if the Brodie–Russell “coagulometer,” as it was referred to, had been able to quantify how much the clot indented with the puff of air, it would have been able to provide information on an important physical property of the clot—specifically its shear modulus.
In this issue of the journal, we feature 4 studies based on a new device called the Quantra® system (HemoSonics, Charlottesville, VA), which utilizes a new technique to estimate the shear modulus, or strength, of a clot.2–5 Also known as modulus of rigidity and usually denoted by “G,” shear modulus is defined as the shear stress divided by the shear strain (Figure). It represents the platelet–fibrinogen interactions because of thrombin and Factor XIII,6 but it is also influenced by hematocrit and acidosis.7 As explained by Quantra’s developers, SEER (sonic estimation of elasticity via resonance) sonorheometry uses ultrasound pulses to vibrate a sample of blood.2 The resulting oscillations of the sample, which are “heard” using the device, are related to the clot’s stiffness (ie, its shear modulus). Using ultrasound to determine this parameter has some potential advantages over the current point-of-care devices that use mechanical means to determine the shear modulus of a clot.
Many clinicians are familiar with the basic principles of the TEG® (Haemonetics Corporation, Braintree, MA) and ROTEM® (Tem International GmbH, Munich, Germany) systems. Both consist of a pin suspended in a cup of blood, one of which oscillates. When clot begins to form between the pin and walls of the cup, the pin’s movement becomes coupled with that of the cup (or vice versa if it is the pin that is rotating), and its displacement can be displayed graphically.8 The magnitude of displacement is commonly referred to as the “clot amplitude” or “clot firmness” and is related to the strength of the clot connecting the pin and cup. Rather than using rotational forces, Sonoclot® (Sienco Inc, Boulder, CO) vertically oscillates a probe, which experiences increased impedance to movement as clot forms.8 All 3 of these devices provide indirect measurements of clot strength by applying mechanical stress. One of the problems with this technique is that the applied mechanical stress is actually strong enough to alter the clot formation.9 Thus, the instruments themselves have an effect on the exact variable they are trying to measure. This situation is not ideal when trying to measure subtle changes.
Using SEER technology to determine the shear modulus should theoretically overcome this problem of the mechanical devices. It is interesting to note that in the study by Reynolds et al, “clot stiffness” as measured by ultrasound was consistently higher compared with “G” as measured by TEG®.3 The higher the clot stiffness, the greater the difference between these 2 measurements. The TEG® platform provides the “G” parameter by using the following equation:
where A = amplitude of the clot.
Although “clot stiffness” and “G” are not directly substitutable, they are attempting to measure the same thing. This finding would indicate that the clot seen, or perhaps more aptly “heard,” using the Quantra® system is different than what the TEG® is measuring.
In 2 other SEER-related articles this month, Huffmyer et al4 and Naik et al5 compared the correlation of the Quantra® device parameters with those of ROTEM® in cardiac and major spine surgery, respectively. Although “clot stiffness” by Quantra® and the 10-minute EXTEM amplitude as measured by ROTEM® had a degree of correlation in both studies, it again needs to be emphasized that these are not directly comparable measurements. There is a nonlinear relationship between shear modulus and clot amplitude.10 In fact, this brings up one of the problems with the way clinicians tend to view clot strength.
Strictly speaking, a clot does not have “amplitude,” so designing interventions to affect this value are potentially flawed. Elasticity is an actual physical property of the clot and can be calculated from both TEG® and ROTEM® amplitudes (clot elasticity = [100 × A]/[100 – A]; A = amplitude). It should be noted that “G” is simply clot elasticity multiplied by 50, although the validity of calculating the shear modulus in this way has recently been questioned.11 In any event, the nonlinear relationship between amplitude and clot elasticity means that small changes in amplitude, which may go unnoticed by the clinician, may actually reflect significant changes in clot elasticity, which is probably the actual clot parameter of interest. As pointed out in a recent review by Solomon et al,12 clot elasticity data, rather than amplitude data, may be more appropriate in determining the platelet contribution to clot strength.
SEER sonorheometry should theoretically be able to detect a wider range of clot structure, or at least clot strength. A better signal that something is wrong may allow earlier and/or more precise selection of hemostatic blood products for quicker and more efficient correction of coagulopathy. Prediction of thrombotic risk with viscoelastic testing has, to this point, relied almost exclusively on amplitude parameters.13 By using a more sensitive measurement, perhaps something reflecting true shear modulus, identification of hypercoagulable states may be improved. The one certainty is that thresholds for one platform cannot simply be transferred over to another. This month’s collection of articles is only the preliminary step for investigating a new technology for assessing clot strength, and prospective interventional studies are clearly needed. The Quantra® device is currently for research use only, and it is not yet US Food and Drug Administration-approved.
A-mode (amplitude) ultrasound, the oldest of modes, displayed a 1-dimensional graph of the strength of returning echoes over time. B-mode (brightness) ultrasound enabled the creation of 2-dimensional images and represented the advancement in technology that aided in the diagnosis of disease. Whether SEER sonorheometry represents a similar advancement in coagulation monitoring remains to be seen, but there is little doubt that Brodie and Russell would be amazed at how far their “coagulometer” has come.
Name: Roman M. Sniecinski, MD.
Contribution: This author helped write the manuscript.
Conflicts of Interest: Roman M. Sniecinski receives research funding from Grifols and is on the Advisory Board; and he receives research funding from Shire Viropharma.
Name: Kenichi A. Tanaka, MD, MSc.
Contribution: This author helped write the manuscript.
Conflicts of Interest: Kenichi A. Tanaka receives research funding from ROTEM and CytoSorb; and he is on the Data Safety Monitoring Board for Octapharma.
This manuscript was handled by: Maxime Cannesson, MD, PhD.
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