Viscoelastic testing: an illustrated review of technology and clinical applications

Viscoelastic testing (VET), including thromboelastography and thromboelastometry, provides a rapid and comprehensive picture of whole blood coagulation dynamics and hemostasis that can be reviewed and evaluated at the point-of-care. This technology is over 50 years old; however, over the past few years, there has been a significant increase in research examining the use of VET. Best practice guidelines for the use of VET exist in both the United States and Europe, particularly for elective cardiac surgery, although recommendations for implementation are somewhat limited in some clinical areas by the lack of studies constituting high-grade evidence. Other challenges to implementation surround validation of the technology in some care settings as well as lack of training. Nevertheless, there is a wide range of potential clinical applications, such as treating coagulopathies in liver disease and transplant surgery, critical care, as well as within obstetrical hemorrhage. In this illustrated review, we provide an overview of viscoelastic testing technology (also called viscoelastic hemostatic assays) and describe how the assays can be used to provide a broad overview of hemostasis from clot formation to clot lysis, while highlighting the contribution of coagulation factors and platelets. We then summarize the major clinical applications for viscoelastic testing, including more recent applications, such as in COVID-19. Each section describes the clinical context, and key publications, followed by a representative algorithm and key guidelines


Viscoelastic testing: technology and principles
The viscoelastic tracing [3] Taking a distinct shape, the viscoelastic tracing captures the cellular and plasmatic elements involved in the hemostasis process.
The overall tracing can offer insight to an individual's ex vivo whole blood clot formation status. The timepoints of the viscoelastic trace are simply divided into the coagulation and clot lysis stages, which can then be further broken down into additional parameters including clot initiation, clot kinetics and clot strength.

LY30
In healthy individuals, hemostasis is a tightly orchestrated process that culminates at the formation of a platelet-fibrin clot at the site of endothelial injury, followed by localized clot breakdown, known as fibrinolysis. Hypercoagulable (tendency to clot) Hypocoagulable (tendency to bleed)

Viscoelastic testing for hemostasis management
There are a number of pathophysiologic mechanisms, either congenital or acquired, that can lead to hemostatic disturbances that sway the pendulum toward excessive bleeding or clotting. These imbalances can be captured and projected through the shape of the viscoelastic tracing. When applied clinically, viscoelastic testing is designed to support and guide, and not replace, clinical judgement.

" Both the consultants and ASA [American Society of Anesthesiologists] members agree that if
coagulopathy is suspected, obtain viscoelastic assays (e.g., TEG and ROTEM), when available, as well as platelet count. They both strongly agree that if viscoelastic assays are not available, obtain standard coagulation tests (e.g., INR, aPTT, fibrinogen concentration), as well as platelet count for monitoring. " Practice guidelines for perioperative blood management ASA 2015 [21] Section 1.

Cardiovascular surgery " We recommend the use of standardised VHA-guided haemostatic algorithms with pre-defined intervention triggers [Evidence Grade 1B] "
Management of severe perioperative bleeding ESA 2016 [22] " The evidence supports the use of perioperative point-of-care testing in patients having cardiac surgery to reduce transfusion requirements. Furthermore, it should be noted that most of the published studies included only viscoelastic coagulation tests… Cut-off levels for non-acceptable intraoperative and postoperative platelet function with the different devices and the subsequent interventions are yet to be determined. " EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery 2018 [23] Key guidelines Suggested treatment algorithm for postsurgical bleeding in cardiac surgery patients [14] Rewarmed If ACT elevated, give additional protamine and repeat ACT HARTMANN ET AL.  [24] " Neither platelet function testing nor genetic testing can be recommended for tailoring DAPT. It may be considered in specific situations (e.g., patients suffering from recurrent adverse events) if the results may change the treatment strategy. This is the case for patients undergoing CABG who are exposed to DAPT " ESC/EACTS focused update on dual antiplatelet therapy in coronary artery disease [26] ADP, adenosine diphosphate; CAGB, coronary artery bypass graft; DAPT, dual antiplatelet therapy; PFT, platelet function tests

" We recommend that resuscitation measures be continued using a goal-directed strategy, guided by standard laboratory coagulation values and/or VEM (Grade 1B)… we suggest the use of POC platelet function devices as an adjunct to standard laboratory and/or POC coagulation monitoring in patients with suspected platelet dysfunction. (Grade 2C). "
European Multidisciplinary Task Force for Advanced Bleeding Care in Trauma [33] " In the setting of severe trauma, results are available more quickly with VETs than with laboratory tests. The GIHP proposes that VETs can be used for the early diagnosis of coagulopathy. The GIHP proposes that VETs, which have a poor performance in diagnosing the activation of fibrinolysis, should not guide the administration of tranexamic acid but that it should be administered as soon as possible. " French Working Group on Perioperative Haemostasis 2019 [36] " Once major bleeding has been controlled and the rate of transfusion has slowed it is appropriate to switch to a laboratory-or point-of-care (POC)-based transfusion. "

Key data: thromboelastography assays reduce blood product use in patients with cirrhosis and/or undergoing liver transplantation in a meta-analysis of 5 randomised controlled trials [39]
The study was a Meta-analysis of pooled data from 5 randomized controlled trials of patients with liver disease. Four studies reported data on platelet use that could be combined with meta-analysis methods.

Society of Critical Care Medicine: Guidelines for the Management of Adult Acute and Acute-on-Chronic
Liver Failure in the ICU [43] "Further study of global measures of coagulation, such as TEG ® and ROTEM ® , to determine appropriate cutoffs for therapeutic intervention are urgently needed. " AGA Clinical Practice Update: Coagulation in Cirrhosis [44] "Global assays such as rotational thromboelastometry (ROTEM)/thromboelastography (TEG) may be an attractive means to reassure the proceduralist that hemostasis is "normal" as these assays are frequently normal despite prolonged coagulation times. " Periprocedural management of patients with cirrhosis ISTH 2022 [45] Key guidelines

Clinical context
Altered hemostasis in pregnancy is associated with coagulation changes that may lead to bleeding or thrombosis events, including postpartum hemorrhage.
Viscoelastic testing can be used to assess patient coagulopathy and, in certain patient populations, the risk of postpartum hemorrhage prior to delivery [46].
Viscoelastic testing-guided algorithms may also be used to direct blood component transfusion requirements in postpartum hemorrhage patients.
Further trials, particularly randomized controlled trials, are required to assess the effect of viscoelastic testing-guided protocols on clinical outcomes in obstetric patients.

Key data: management of postpartum hemorrhage with ROTEM ® Delta led to reduced blood product requirements in a retrospective cohort study of 86 patients (p<0.001 for all) [47]
Reproduced with permissions from Snegovskikh 2018 [47] Key publications

Treatment algorithm for postpartum hemorrhage
The presented algorithm is a collation of multiple sources covering both TEG ® and ROTEM ® methodology, including a clinically validated algorithm by OBS Cymru; Bell. 2020. [52] Algorithm reproduced with permissions from Dias 2022. [53] A postpartum hemorrhage TEG ® and ROTEM ® treatment algorithm (not clinically validated) " We recommend monitoring hemostasis with either PT/aPTT and Clauss fibrinogen or POCTs using thromboelastometry during PPH. If bleeding persists serial measures should be performed.

If thromboelastometry is used, blood component replacement should be based on a local algorithm and a quality control protocol agreed with hematology. "
Management of coagulopathy associated with PPH; guidance from the SSC of the ISTH [54] " We recommend assessing haemostatic competence and risk of coagulopathy in severe ongoing

PPH through laboratory tests (platelet count, PT, international normalised ratio [INR], aPTT, fibrinogen level) or viscoelastic haemostatic tests to guide appropriate, goal-directed use of haemostatic blood components and pro-haemostatic agents [Evidence Grade 1B]. "
NATA consensus statement on prevention and treatment of PPH [55] " Risk awareness and early recognition of severe PPH are essential.
[Evidence base C]

In severe PPH we suggest a VHA-guided intervention protocol. [Evidence base 2C]. "
Management of severe perioperative bleeding ESA 2016 [22] Key guidelines aPTT, activated partial thromboplastin clotting time; PPH, postpartum hemorrhage; PT, prothrombin time; POCT, point-of-care tests; INR, international normalized ratio; VHA, viscoelastic hemostatic assay Estimated blood loss approaching 500 mL (vaginal delivery) or 1000 mL (caesarean section) Ongoing bleeding or clinical concern No blood products required Clinical concern or suspected bleeding (including concealed bleeding) >500 mL

Implementing viscoelastic testing in clinical care settings
Challenges associated with viscoelastic testing in a clinical setting Cup and pin mechanism does not represent in vivo vascular mechanics Insensitivity for detecting von Willebrand factor and minor/moderate fibrinolytic activity. Low hematocrit (as seen in anemia) may reduce accuracy of viscoelastic testing [67] No detection of platelet factor receptor defects without additional testing Results are not interchangeable between technologies (e.g., TEG ® and ROTEM ® ), and between device models Lack of acceptance, especially by traditional hematologists/pathologists (due to limited level of evidence), and overall lack of awareness/training Relative complexity of visual processes and need for training Potential for inter-user variability due to lack of training

Lack of regulatory clearance in pediatric settings
Lack of level 1 evidence from high quality randomized controlled trials