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Clinical Research on Viscoelastic Testing
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Clinical Research on Viscoelastic Testing

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Hematology".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 62506

Special Issue Editors

Dr. Mark M. Walsh

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Guest Editor
Departments of Emergency Medicine and Internal Medicine, Saint Joseph Regional Medical Center, Indiana University School of Medicine South Bend Campus, 5215 Holy Cross Parkway, Mishawaka, IN 46545, USA
Dr. Mirjam Bachler

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Guest Editor
1. UMIT-Tirol, The Tyrolean Private University, Institute for Sports Medicine, Alpine Medicine and Health Tourism, Private University for Health Sciences Medical Informatics and Technology, Hall, Austria
2. Department for Anesthesiology and Critical Care Medicine, Tirol Kliniken GmbH, Innsbruck, Austria

Special Issue Information

Dear Colleagues,

Viscoelastic testing contributes substantially to better coagulatory monitoring and treatment of patients and can therefore be of great use in various areas of patient care. The advantages of this coagulation evaluation method are clear: results are available within minutes, whole blood coagulation is assessed, and procedures are operator-friendly.

Viscoelastic testing can be used for individualized therapy to elucidate potential hemostatic deficiencies. Especially in trauma care, viscoelastic tests are increasingly used to identify, in a timely manner, effective, goal-directed patient management. It provides a quantifiable basis for personalized treatments with the appropriate coagulation factor concentrates and transfusions in trauma as well as surgical patients. Additionally, quick results guarantee reduced blood loss and therefore improved outcome. Recent advances in assay and reagent configurations make it possible to differentiate DOACs that act on FX or thrombin, namely directly in the emergency room where time is a most precious resource.

Furthermore, the only way to evaluate the fibrinolytic status of a patient is by viscoelastic testing, which is not only important for trauma-associated hyperfibrinolysis and the targeted administration of tranexamic acid, but also in the prevention and treatment of postpartum hemorrhage.

During a patient’s stay in the intensive care unit (ICU), viscoelastic testing can contribute to a more precise differential diagnosis of acute and subacute disturbances in hemostasis and thus improve patient treatment. Bleeding situations can be evaluated and treated in a timely manner. Especially in COVID-19 patients, a hypercoagulable and hypofibrinolytic state can be detected and counteracted early.

Even though research in the field of viscoelastic testing has increased remarkably in recent years, this additional dimension of coagulation assessment has not entered treatment guidelines for the management of patients with hemostatic alterations and acute coagulopathy. Therefore, more studies are needed that emphasize the use of viscoelastic assays in the management of trauma, surgical, and critically ill patients.

This Special Issue on "Viscoelastic Testing" aims to collect recent studies and reviews on the utility of viscoelastic testing in different patient populations to expand current knowledge and advise users in various clinical situations.

Dr. Mark M. Walsh
Dr. Mirjam Bachler
Guest Editors

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Research

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12 pages, 853 KiB  
Article
Conventional and Pro-Inflammatory Pathways of Fibrinolytic Activation in Non-Traumatic Hyperfibrinolysis
by Johannes Zipperle, Bernhard Ziegler, Herbert Schöchl, Wolfgang Voelckel, Peter Dungel, Janne Cadamuro, Marcin Osuchowski, Christoph J. Schlimp and Daniel Oberladstätter
J. Clin. Med. 2022, 11(24), 7305; https://doi.org/10.3390/jcm11247305 - 9 Dec 2022
Cited by 2 | Viewed by 1584
Abstract
Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature [...] Read more.
Hyperfibrinolysis (HF) frequently occurs after severe systemic hypoperfusion during major trauma and out-of-hospital cardiac arrest (OHCA). In trauma-induced HF, hypoperfusion, the activation of protein C (APC), and the release of tissue plasminogen activator (t-PA) have been identified as the driving elements of premature clot breakdown. The APC pathway also plays a role in inflammatory responses such as neutrophil extracellular trap formation (NETosis), which might contribute to lysis through cleavage of fibrin by neutrophil elastases. We investigated whether the APC and the plasminogen pathway were general drivers of HF, even in the absence of a traumatic incident. Additionally, we were interested in inflammatory activation such as the presence of NETs as potential contributing factors to HF. A total of 41 patients with OHCA were assigned to a HF and a non-HF group based on maximum lysis (ML) in thromboelastometry. Thrombin–antithrombin (TAT)-complex, soluble thrombomodulin (sTM), APC–PC inhibitor complex, t-PA, PAI-1, t-PA–PAI-1 complex, plasmin–antiplasmin (PAP), d-dimers, neutrophil elastase, histonylated DNA (hDNA) fragments, and interleukin-6 were assessed via immunoassays in the HF group vs. non-HF. APC–PC inhibitor complex is significantly higher in HF patients. Antigen levels of t-PA and PAI-1 do not differ between groups. However, t-PA activity is significantly higher and t-PA–PAI-1 complex significantly lower in the HF group. Consistent with these results, PAP and d-dimers are significantly elevated in HF. HDNA fragments and neutrophil elastase are not elevated in HF patients, but show a high level of correlation, suggesting NETosis occurs in OHCA as part of inflammatory activation and cellular decay. Just as in trauma, hypoperfusion, the activation of protein C, and the initiation of the plasminogen pathway of fibrinolysis manifest themselves in the HF of cardiac arrest. Despite features of NETosis being detectable in OHCA patients, early pro-inflammatory responses do not appear be associated with HF in cardiac arrest. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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10 pages, 3524 KiB  
Article
Thrombelastography Compared with Multiple Impedance Aggregometry to Assess High On-Clopidogrel Reactivity in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
by Diona Gjermeni, Hannah Vetter, Sofia Szabó, Viktoria Anfang, Stefan Leggewie, David Hesselbarth, Daniel Duerschmied, Dietmar Trenk and Christoph B. Olivier
J. Clin. Med. 2022, 11(14), 4237; https://doi.org/10.3390/jcm11144237 - 21 Jul 2022
Cited by 1 | Viewed by 2156
Abstract
Background: High on-clopidogrel platelet reactivity (HPR) following percutaneous coronary intervention (PCI) is associated with increased ischemic risk. It is unclear whether conventional definitions of HPR apply to patients with concomitant oral anticoagulation (OAC). This study aimed to compare the performance of multiple platelet [...] Read more.
Background: High on-clopidogrel platelet reactivity (HPR) following percutaneous coronary intervention (PCI) is associated with increased ischemic risk. It is unclear whether conventional definitions of HPR apply to patients with concomitant oral anticoagulation (OAC). This study aimed to compare the performance of multiple platelet aggregometry (MEA) and thrombelastography (TEG) to detect HPR in patients with atrial fibrillation (AF) and indication for an OAC. Methods: In this observational single-center cohort study, MEA and TEG were performed in patients with AF with an indication for OAC on day 1 to 3 after PCI. The primary outcome was HPR as assessed by MEA (ADP area under the curve ≥ 46 units [U]) or TEG (MAADP ≥ 47 mm), respectively. The secondary exploratory outcomes were a composite of all-cause death, myocardial infarction (MI) or stroke and bleeding, as defined by the International Society on Thrombosis and Hemostasis, at 6 months. Results: Platelet function of 39 patients was analyzed. The median age was 78 (interquartile range [IQR] was 72–82) years. 25 (64%) patients were male, and 19 (49%) presented with acute coronary syndrome. All patients received acetylsalicylic acid and clopidogrel prior to PCI. Median (IQR) ADP-induced aggregation, MAADP, TRAP-induced aggregation, and MAthrombin were 9 (6–15) U, 50 (43–60) mm, 54 (35–77) U and 65 (60–67) mm, respectively. The rate of HPR was significantly higher if assessed by TEG compared with MEA (25 [64%] vs. 1 [3%]; p < 0.001). Within 6 months, four (10%) deaths, one (3%) MI and nine (23%) bleeding events occurred. Conclusion: In patients with AF undergoing PCI, the rates of HPR detected by TEG were significantly higher compared with MEA. Conventional cut-off values for HPR as proposed by consensus documents may need to be re-evaluated for this population at high ischemic and bleeding risk. Further studies are needed to assess the association with outcomes. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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10 pages, 2633 KiB  
Article
Operability of a Resonance-Based Viscoelastic Haemostatic Analyzer in the High-Vibration Environment of Air Medical Transport
by Johannes Zipperle, Bernhard Ziegler, Herbert Schöchl, Wolfgang Voelckel, Christoph J. Schlimp and Daniel Oberladstätter
J. Clin. Med. 2022, 11(13), 3630; https://doi.org/10.3390/jcm11133630 - 23 Jun 2022
Cited by 3 | Viewed by 1292
Abstract
Trauma and bleeding are associated with a high mortality, and most of these deaths occur early after injury. Viscoelastic haemostatic tests have gained increasing importance in goal-directed transfusion and bleeding management. A new generation of small-sized and thus portable ultrasound-based viscoelastic analysers have [...] Read more.
Trauma and bleeding are associated with a high mortality, and most of these deaths occur early after injury. Viscoelastic haemostatic tests have gained increasing importance in goal-directed transfusion and bleeding management. A new generation of small-sized and thus portable ultrasound-based viscoelastic analysers have been introduced in clinical practice. We questioned whether a promising candidate can be used in emergency helicopters, with a focus on the susceptibility to vibration stress. We investigated whether the high vibration environment of an emergency helicopter would affect the operability of an ultrasound-based viscoelastic analyser and would yield reproducible results in flight and on the ground. We drew blood from 27 healthy volunteers and performed simultaneous analyses on two TEG 6s. Each measurement was performed in-flight on board an Airbus H135 emergency helicopter and was repeated on the ground, close to the flight area. Results from both measurements were compared, and the recorded tracings and numeric results were analysed for artifacts. Vibratometric measurements were performed throughout the flight in order to quantify changes in the magnitude and character of vibrations in different phases of helicopter operation. The high vibration environment was associated with the presence of artifacts in all recorded tracings. There were significant differences in citrated Kaolin + Heparinase measurements in-flight and on the ground. All other assays increased in variability but did not show significant differences between the two time points. We observed numerous artifacts in viscoelastic measurements that were performed in flight. Some parameters that were obtained from the same sample showed significant differences between in-flight and on-ground measurements. Performing resonance-based viscoelastic tests in helicopter medical service is prone to artifacts. However, a 10 min delay between initiation of measurement and take-off might produce more reliable results. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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15 pages, 3423 KiB  
Article
Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy?
by Brian S. Bull, Karen L. Hay and Paul C. Herrmann
J. Clin. Med. 2022, 11(8), 2084; https://doi.org/10.3390/jcm11082084 - 7 Apr 2022
Cited by 1 | Viewed by 1990
Abstract
Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in corona virus disease 2019 (COVID-19) associated coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill COVID-19 patients with an associated elevation of d-dimer. [...] Read more.
Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in corona virus disease 2019 (COVID-19) associated coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill COVID-19 patients with an associated elevation of d-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein, we describe a novel method illuminating aspects of this unexplored area. In addition, we created an in vitro blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing the determination of soluble fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows the determination of the SF level at which fibrin microclots begin to form. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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10 pages, 1600 KiB  
Article
Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro® Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients
by Daniel Oberladstätter, Christoph J. Schlimp, Johannes Zipperle, Marcin F. Osuchowski, Wolfgang Voelckel, Oliver Grottke and Herbert Schöchl
J. Clin. Med. 2021, 10(16), 3476; https://doi.org/10.3390/jcm10163476 - 6 Aug 2021
Cited by 11 | Viewed by 2962
Abstract
Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, [...] Read more.
Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro® Russell’s viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all p < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all p < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers’ blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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16 pages, 491 KiB  
Article
Preventing Thrombohemorrhagic Complications of Heparinized COVID-19 Patients Using Adjunctive Thromboelastography: A Retrospective Study
by Connor M. Bunch, Anthony V. Thomas, John E. Stillson, Laura Gillespie, Rashid Z. Khan, Nuha Zackariya, Faadil Shariff, Mahmoud Al-Fadhl, Nicolas Mjaess, Peter D. Miller, Michael T. McCurdy, Daniel H. Fulkerson, Joseph B. Miller, Hau C. Kwaan, Ernest E. Moore, Hunter B. Moore, Matthew D. Neal, Peter L. Martin, Mark L. Kricheff and Mark M. Walsh
J. Clin. Med. 2021, 10(14), 3097; https://doi.org/10.3390/jcm10143097 - 14 Jul 2021
Cited by 17 | Viewed by 3058
Abstract
Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests [...] Read more.
Background: The treatment of COVID-19 patients with heparin is not always effective in preventing thrombotic complications, but can also be associated with bleeding complications, suggesting a balanced approach to anticoagulation is needed. A prior pilot study supported that thromboelastography and conventional coagulation tests could predict hemorrhage in COVID-19 in patients treated with unfractionated heparin or enoxaparin, but did not evaluate the risk of thrombosis. Methods: This single-center, retrospective study included 79 severely ill COVID-19 patients anticoagulated with intermediate or therapeutic dose unfractionated heparin. Two stepwise logistic regression models were performed with bleeding or thrombosis as the dependent variable, and thromboelastography parameters and conventional coagulation tests as the independent variables. Results: Among all 79 patients, 12 (15.2%) had bleeding events, and 20 (25.3%) had thrombosis. Multivariate logistic regression analysis identified a prediction model for bleeding (adjusted R2 = 0.787, p < 0.001) comprised of increased reaction time (p = 0.016), decreased fibrinogen (p = 0.006), decreased D-dimer (p = 0.063), and increased activated partial thromboplastin time (p = 0.084). Multivariate analysis of thrombosis identified a weak prediction model (adjusted R2 = 0.348, p < 0.001) comprised of increased D-dimer (p < 0.001), decreased reaction time (p = 0.002), increased maximum amplitude (p < 0.001), and decreased alpha angle (p = 0.014). Adjunctive thromboelastography decreased the use of packed red cells (p = 0.031) and fresh frozen plasma (p < 0.001). Conclusions: Significantly, this study demonstrates the need for a precision-based titration strategy of anticoagulation for hospitalized COVID-19 patients. Since severely ill COVID-19 patients may switch between thrombotic or hemorrhagic phenotypes or express both simultaneously, institutions may reduce these complications by developing their own titration strategy using daily conventional coagulation tests with adjunctive thromboelastography. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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Review

Jump to: Research, Other

23 pages, 928 KiB  
Review
Viscoelastic Hemostatic Assays for Orthopedic Trauma and Elective Procedures
by Christiaan N. Mamczak, Jacob Speybroeck, John E. Stillson, Joseph Dynako, Andres Piscoya, Ethan E. Peck, Michael Aboukhaled, Emily Cancel, Michael McDonald, Diego Garcia, John Lovejoy, Stephanie Lubin, Robert Stanton and Matthew E. Kutcher
J. Clin. Med. 2022, 11(14), 4029; https://doi.org/10.3390/jcm11144029 - 12 Jul 2022
Cited by 2 | Viewed by 2722
Abstract
The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the [...] Read more.
The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the real-time coagulation and fibrinolytic status in both orthopedic trauma and elective orthopedic surgery. Trauma-induced coagulopathy—a spectrum of abnormal coagulation phenotypes including clotting factor depletion, inadequate thrombin generation, platelet dysfunction, and dysregulated fibrinolysis—remains a potentially fatal complication in severely injured and/or hemorrhaging patients whose timely diagnosis and management are aided by the use of VHAs. Furthermore, VHAs are an invaluable compliment to common coagulation tests by facilitating the detection of hypercoagulable states commonly associated with orthopedic injury and postoperative status. The use of VHAs to identify hypercoagulability allows for an accurate venous thromboembolism (VTE) risk assessment and monitoring of VTE prophylaxis. Until now, the data have been insufficient to permit an individualized approach with regard to dosing and duration for VTE thromboprophylaxis. By incorporating VHAs into routine practice, orthopedic surgeons will be better equipped to diagnose and treat the complete spectrum of coagulation abnormalities faced by orthopedic patients. This work serves as an educational primer and up-to-date review of the current literature on the use of VHAs in orthopedic surgery. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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26 pages, 856 KiB  
Review
“In Less than No Time”: Feasibility of Rotational Thromboelastometry to Detect Anticoagulant Drugs Activity and to Guide Reversal Therapy
by Vittorio Pavoni, Lara Gianesello, Duccio Conti, Piercarlo Ballo, Pietro Dattolo, Domenico Prisco and Klaus Görlinger
J. Clin. Med. 2022, 11(5), 1407; https://doi.org/10.3390/jcm11051407 - 4 Mar 2022
Cited by 19 | Viewed by 6765
Abstract
Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early. In certain situations, [...] Read more.
Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early. In certain situations, such as bleeding, urgent invasive procedures, and surgical settings, the evaluation of anticoagulant levels and the monitoring of reversal therapy appear essential. Standard coagulation tests (i.e., activated partial thromboplastin time (aPTT) and prothrombin time (PT)) can be normal, and the turnaround time can be long. While the role of viscoelastic hemostatic assays (VHAs), such as rotational thromboelastometry (ROTEM), has successfully increased over the years in the management of bleeding and thrombotic complications, its usefulness in detecting anticoagulants and their reversal still appears unclear. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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15 pages, 513 KiB  
Review
Use of Thromboelastography and Rotational Thromboelastometry in Otolaryngology: A Narrative Review
by Mathew K. Marsee, Faisal S. Shariff, Grant Wiarda, Patrick J. Watson, Ali H. Sualeh, Toby J. Brenner, Max L. McCoy, Hamid D. Al-Fadhl, Alexander J. Jones, Patrick K. Davis, David Zimmer and Craig Folsom
J. Clin. Med. 2022, 11(4), 1119; https://doi.org/10.3390/jcm11041119 - 20 Feb 2022
Cited by 1 | Viewed by 2817
Abstract
In the field of otolaryngology—head and neck surgery (ENT), coagulopathies present unique diagnostic and therapeutic challenges. In both hyper- and hypocoagulable patients, management of coagulopathies requires intricate attention to the nature of hemostatic competence. Common coagulation tests (CCTs) offer only a snapshot of [...] Read more.
In the field of otolaryngology—head and neck surgery (ENT), coagulopathies present unique diagnostic and therapeutic challenges. In both hyper- and hypocoagulable patients, management of coagulopathies requires intricate attention to the nature of hemostatic competence. Common coagulation tests (CCTs) offer only a snapshot of hemostatic competence and do not provide a clear insight into the patient’s real-time hemostatic condition. Viscoelastic tests (VETs) offer a holistic and concurrent picture of the coagulation process. Although VETs have found prominent utilization in hepatic transplants, obstetrics, and emergent surgical settings, they have not been fully adopted in the realm of otolaryngology. The objective of this manuscript is to provide an overview of the literature evaluating the current utilization and possible future uses of VETs in the field of otolaryngology. The authors performed a comprehensive literature search of the utilization of VETs in otolaryngology and identified applicable studies that included descriptions of viscoelastic testing. Twenty-five studies were identified in this search, spanning topics from head and neck oncology, microvascular free flap reconstruction, obstructive sleep apnea, adenotonsillectomy, facial trauma, and epistaxis. The applicability of VETs has been demonstrated in head and neck oncology and microvascular free flap management, although their pervasiveness in practice is limited. Underutilization of VETs in the field of otolaryngology may be due to a lack of familiarity of the tests amongst practitioners. Instead, most otolaryngologists continue to rely on CCTs, including PT, PTT, INR, CBC, fibrinogen levels, and thrombin time. Learning to perform, interpret, and skillfully employ VETs in clinical and operative practice can greatly improve the management of coagulopathic patients who are at increased risk of bleeding or thrombosis. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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22 pages, 950 KiB  
Review
Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices
by Oksana Volod, Connor M. Bunch, Nuha Zackariya, Ernest E. Moore, Hunter B. Moore, Hau C. Kwaan, Matthew D. Neal, Mahmoud D. Al-Fadhl, Shivani S. Patel, Grant Wiarda, Hamid D. Al-Fadhl, Max L. McCoy, Anthony V. Thomas, Scott G. Thomas, Laura Gillespie, Rashid Z. Khan, Mahmud Zamlut, Peter Kamphues, Dietmar Fries and Mark M. Walsh
J. Clin. Med. 2022, 11(3), 860; https://doi.org/10.3390/jcm11030860 - 7 Feb 2022
Cited by 45 | Viewed by 8235
Abstract
Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research [...] Read more.
Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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21 pages, 2696 KiB  
Review
TEG®, Microclot and Platelet Mapping for Guiding Early Management of Severe COVID-19 Coagulopathy
by Gert Jacobus Laubscher, Petrus Johannes Lourens, Chantelle Venter, Douglas B Kell and Etheresia Pretorius
J. Clin. Med. 2021, 10(22), 5381; https://doi.org/10.3390/jcm10225381 - 18 Nov 2021
Cited by 24 | Viewed by 13752
Abstract
An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation [...] Read more.
An important component of severe COVID-19 disease is virus-induced endothelilitis. This leads to disruption of normal endothelial function, initiating a state of failing normal clotting physiology. Massively increased levels of von Willebrand Factor (VWF) lead to overwhelming platelet activation, as well as activation of the enzymatic (intrinsic) clotting pathway. In addition, there is an impaired fibrinolysis, caused by, amongst others, increased levels of alpha-(2) antiplasmin. The end result is hypercoagulation (proven by thromboelastography® (TEG®)) and reduced fibrinolysis, inevitably leading to a difficult-to-overcome hypercoagulated physiological state. Platelets in circulation also plays a significant role in clot formation, but they themselves may also drive hypercoagulation when they are overactivated due to the interactions of their receptors with the endothelium, immune cells or circulating inflammatory molecules. From the literature it is clear that the role of platelets in severely ill COVID-19 patients has been markedly underestimated or even ignored. We here highlight the value of early management of severe COVID-19 coagulopathy as guided by TEG®, microclot and platelet mapping. We also argue that the failure of clinical trials, where the efficacy of prophylactic versus therapeutic clexane (low molecular weight heparin (LMWH)) were not always successful, which may be because the significant role of platelet activation was not taken into account during the planning of the trial. We conclude that, because of the overwhelming alteration of clotting, the outcome of any trial evaluating an any single anticoagulant, including thrombolytic, would be negative. Here we suggest the use of the degree of platelet dysfunction and presence of microclots in circulation, together with TEG®, might be used as a guideline for disease severity. A multi-pronged approach, guided by TEG® and platelet mapping, would be required to maintain normal clotting physiology in severe COVID-19 disease. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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24 pages, 1804 KiB  
Review
Viscoelastic Testing and Coagulopathy of Traumatic Brain Injury
by Jamie L. Bradbury, Scott G. Thomas, Nikki R. Sorg, Nicolas Mjaess, Margaret R. Berquist, Toby J. Brenner, Jack H. Langford, Mathew K. Marsee, Ashton N. Moody, Connor M. Bunch, Sandeep R. Sing, Mahmoud D. Al-Fadhl, Qussai Salamah, Tarek Saleh, Neal B. Patel, Kashif A. Shaikh, Stephen M. Smith, Walter S. Langheinrich, Daniel H. Fulkerson and Sherry Sixta
J. Clin. Med. 2021, 10(21), 5039; https://doi.org/10.3390/jcm10215039 - 28 Oct 2021
Cited by 11 | Viewed by 5363
Abstract
A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays—such as prothrombin time, partial thromboplastin time, and international normalized ratio—have historically been utilized to assess hemostasis and guide [...] Read more.
A unique coagulopathy often manifests following traumatic brain injury, leading the clinician down a difficult decision path on appropriate prophylaxis and therapy. Conventional coagulation assays—such as prothrombin time, partial thromboplastin time, and international normalized ratio—have historically been utilized to assess hemostasis and guide treatment following traumatic brain injury. However, these plasma-based assays alone often lack the sensitivity to diagnose and adequately treat coagulopathy associated with traumatic brain injury. Here, we review the whole blood coagulation assays termed viscoelastic tests and their use in traumatic brain injury. Modified viscoelastic tests with platelet function assays have helped elucidate the underlying pathophysiology and guide clinical decisions in a goal-directed fashion. Platelet dysfunction appears to underlie most coagulopathies in this patient population, particularly at the adenosine diphosphate and/or arachidonic acid receptors. Future research will focus not only on the utility of viscoelastic tests in diagnosing coagulopathy in traumatic brain injury, but also on better defining the use of these tests as evidence-based and/or precision-based tools to improve patient outcomes. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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22 pages, 1078 KiB  
Review
Viscoelastic Hemostatic Assays for Postpartum Hemorrhage
by Alyson E. Liew-Spilger, Nikki R. Sorg, Toby J. Brenner, Jack H. Langford, Margaret Berquist, Natalie M. Mark, Spencer H. Moore, Julie Mark, Sara Baumgartner and Mary P. Abernathy
J. Clin. Med. 2021, 10(17), 3946; https://doi.org/10.3390/jcm10173946 - 31 Aug 2021
Cited by 13 | Viewed by 3861
Abstract
This article discusses the importance and effectiveness of viscoelastic hemostatic assays (VHAs) in assessing hemostatic competence and guiding blood component therapy (BCT) in patients with postpartum hemorrhage (PPH). In recent years, VHAs such as thromboelastography and rotational thromboelastometry have increasingly been used to [...] Read more.
This article discusses the importance and effectiveness of viscoelastic hemostatic assays (VHAs) in assessing hemostatic competence and guiding blood component therapy (BCT) in patients with postpartum hemorrhage (PPH). In recent years, VHAs such as thromboelastography and rotational thromboelastometry have increasingly been used to guide BCT, hemostatic adjunctive therapy and prohemostatic agents in PPH. The three pillars of identifying hemostatic competence include clinical observation, common coagulation tests, and VHAs. VHAs are advantageous because they assess the cumulative contribution of all components of the blood throughout the entire formation of a clot, have fast turnaround times, and are point-of-care tests that can be followed serially. Despite these advantages, VHAs are underused due to poor understanding of correct technique and result interpretation, a paucity of widespread standardization, and a lack of large clinical trials. These VHAs can also be used in cases of uterine atony, preeclampsia, acute fatty liver of pregnancy, amniotic fluid embolism, placental abruption, genital tract trauma, surgical trauma, and inherited and prepartum acquired coagulopathies. There exists an immediate need for a point-of-care test that can equip obstetricians with rapid results on developing coagulopathic states. The use of VHAs in predicting and treating PPH, although in an incipient state, can fulfill this need. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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14 pages, 283 KiB  
Comment
Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860
by Marion Bareille, Thomas Lecompte, François Mullier and Stéphanie Roullet
J. Clin. Med. 2023, 12(2), 477; https://doi.org/10.3390/jcm12020477 - 6 Jan 2023
Cited by 6 | Viewed by 1314
Abstract
With the advent of new viscoelastometric hemostatic assay (VHA) devices, with ready-to-use cartridge reagents allowing for their use by people without special laboratory skills, the appreciation of the actual clinical value of VHAs in settings such as severe trauma, post-partum hemorrhage, cardiac surgery [...] Read more.
With the advent of new viscoelastometric hemostatic assay (VHA) devices, with ready-to-use cartridge reagents allowing for their use by people without special laboratory skills, the appreciation of the actual clinical value of VHAs in settings such as severe trauma, post-partum hemorrhage, cardiac surgery and liver transplantation still needs to be fully validated. While two of the newest versions remain based on a ‘cup and pin’ system (ROTEM® sigma, ClotPro®), two other new devices (TEG® 6s, Quantra®) rely on very different technologies: clotting blood is no longer in contact with the probe and challenged by oscillation of one of the components but explored with ultrasound exposure. A systematic literature search (including Sonoclot®) retrieved 20 observational studies (19 prospective). Most studies pointed to imperfect agreements, highlighting the non-interchangeability of devices. Only a few studies, often with a limited number of patients enrolled, used a clinical outcome. No study compared VHA results with conventional laboratory assays obtained through a rapid tests panel. Clinical evidence of the utility of the new VHAs largely remains to be proven through randomized clinical trials, with clinically relevant outcomes, and compared to rapid panel hemostasis testing. The availability of new, improved VHA devices provides an impetus and an opportunity to do so. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
16 pages, 1168 KiB  
Systematic Review
The Use of Thromboelastography in Percutaneous Coronary Intervention and Acute Coronary Syndrome in East Asia: A Systematic Literature Review
by Ou Xu, Jan Hartmann, Yi-Da Tang and Joao Dias
J. Clin. Med. 2022, 11(13), 3652; https://doi.org/10.3390/jcm11133652 - 24 Jun 2022
Cited by 2 | Viewed by 2269
Abstract
Dual antiplatelet therapy (DAPT), alongside percutaneous coronary intervention (PCI), is central to the prevention of ischemic events following acute coronary syndrome (ACS). However, response to therapy can vary due to several factors including CYP2C19 gene variation, which shows increased prevalence in East Asian [...] Read more.
Dual antiplatelet therapy (DAPT), alongside percutaneous coronary intervention (PCI), is central to the prevention of ischemic events following acute coronary syndrome (ACS). However, response to therapy can vary due to several factors including CYP2C19 gene variation, which shows increased prevalence in East Asian populations. DAPT responsiveness can be assessed using techniques such as light transmission aggregometry (LTA), VerifyNow® and thromboelastography with the PlateletMapping® assay, and there is increasing focus on the utility of platelet function testing to guide individualized treatment. This systematic literature review of one English and three Chinese language databases was conducted to evaluate the evidence for the utility of thromboelastography in ACS/PCI in East Asia. The search identified 42 articles from the English language and 71 articles from the Chinese language databases which fulfilled the pre-determined inclusion criteria, including 38 randomized controlled trials (RCTs). The identified studies explored the use of thromboelastography compared to LTA and VerifyNow in monitoring patient responsiveness to DAPT, as well as predicting ischemic risk, with some studies suggesting that thromboelastography is better able to detect low DAPT response than LTA. Other studies, including one large RCT, described the use of thromboelastography in guiding the escalation of DAPT, with some evidence suggesting that such protocols reduce ischemic events without increasing the risk of bleeding. There was also evidence suggesting that thromboelastography can be used to identify individuals with DAPT hyporesponsiveness genotypes and could potentially guide treatment by adjusting therapy in patients depending on responsiveness. Full article
(This article belongs to the Special Issue Clinical Research on Viscoelastic Testing)
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