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The interpretations below are provided by Donna Castellone, MS, MT (ASCP) SH for Aniara Diagnostica.

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INTRODUCTION:

Believe it or not the first viscoelastic test was actually developed in Germany in 1948 before the aPTT, which was developed in 1953. It was used in cardiac surgery and transplants.⁽¹⁾ However, it was not widely accepted in laboratories. When the cellular based model of hemostasis was introduced in 1994 it confirmed the role of platelets, RBCs and other cells in the formation of a clot. Different sectors saw the value in that, and as a result the wild west of viscoelastic testing (VET) was born. Clinicians' in the OR saw this as a solution to perioperative bleeding. Analyzers were brought into institutions and samples were tested. The issue was that there was no control by the laboratory over this process. Eventually, the laboratory had to be included. The issues of how to validate the analyzer, as well as where it should be located as a POC analyzer and who was responsible to provide competency all needed to be addressed. It was time to lasso in the wild west. Most of the systems were used in larger academic centers. The pathologist needs to work with clinicians to educate them as to what the analyzer can be used for. It cannot be used to diagnose von Willebrand Disease, but it can be used to guide blood products in a bleeding patient.¹

WHAT'S OUT THERE:

The current analyzers with FDA approval are TEG® Hemostasis Analyzer System (Haemonetics Corp.) and ROTEM® delta (Instrumentation Laboratory) TEG® 6s system (Haemonetics Corp.) and the Quantra® Hemastasis Analyzer (HemoSonics LLC).

Cartridge based viscoelasatic methodologies are based on harmonic resonance-based clot detection and provides increase ease of use and robustness. Testing is used in several clinical contexts: cardiac surgery, transplants, hypercoagulable states such as COVID-19 which was FDA approved in 2021 for coagulation associated coagulopathy. VET guided transfusion algorithms have been shown to reduce blood utilization without worsening patient outcomes. It is also has been used in OB GYN, however, that is considered off label, as there is no FDA approval in that scenario.²

HOW DO YOU VALIDATE?

TEG must be validated just as any other analyzer. The laboratory must be involved in the decision making regarding the selection of the analyzer as well as the location it can best be utilized- POC or within the laboratory. Certain steps must be performed prior to placing the analyzer into use.³

1. Precision testing to evaluate reproducibility and inter-operator variability.
2. Developing local reference ranges or verifying the manufacturer's ranges with a minimum of 20 normal subjects as long as the population matches the ones used to establish RR in the package insert.
   A study looked at 118 normal subjects for a normal RR for TEG and compared it to the manufacturer' range. There were 10 subjects with significantly different results who were outside their range. Extensive coagulation studies revealed no abnormalities within these subjects. Healthy women were found to be more hypercoagulable than men. This supports the recommendation that each institution should determine their own normal values prior to implementing.⁴
3. A quality management program should be determined including running QC, enrolling in PT, evaluation of competency. This should be done to mitigate risks, in particular when the analyzer is run off site. An IQCP should be performed to design and establish control procedures relevant to the local environment, personnel, devices, and patients. The stability of the system, the environment, reagents, and personnel should all be evaluated to ensure devices are robust.⁵
4. Proper development and maintaining standard operating procedures.
5. Inventory management.
6. Assisting and validation of reporting results to comply with all standards.³

Clinicians need to be involved in establishing cut-off values for relevant clinical situations and algorithms for transfusion protocols.³

GUIDELINES AND REQUIREMENTS:

New guide to whole blood viscoelastic assays: hemostasis, testing, cases and applications. CAP TODAY, October 2023. This publication was recently published is an aid to understanding the practical application of the interpretation of VET across clinical settings. It is comprised of three parts. The first is an overview of hemostasis physiology of conventional assays and therapeutic agents. The second looks at the FDA approved assays and the third section included real life case studies.

The CAP requirements have been updated to reflect the situations seen with VET testing.

There is a requirement that states PT testing as well as alternative performance, should be tested within the routine laboratory by personnel that test patient samples. The question was asked if a person can be assisted by another person when looking at a PT sample. It is allowed in morphologic examination, electrophoresis proved patient samples are handled in the same manner. VET testing is now added to this recommendation.⁶

HEM 38700 Viscoelastic testing: If hemostasis analysis is performed in the laboratory and the results are viewable remotely by clinical personnel in real time, did the laboratory promptly communicated analytic errors to the responsible personnel?

The requirement HEM 37165 for Coagulation testing and Therapeutic Anticoagulant Recommendations includes viscoelastic testing in clinically meaningful situations must be available. Recommendations about the utility and limitation of viscoelastic testing in therapeutic clinical situations including monitoring of antiplatelet or anticoagulants.⁶

VET ADVANTAGES:

This method doesn't require any samples processing, no test preparation beyond transfer pipetting or sample tube spiking. It can be processed near the patient and the VET tracing appears in real time providing information within minutes of testing. The tracing can be reviewed remotely and interfaced to a computer to inform clinicians even if performed in the laboratory. Traditional coagulation testing is less expensive. However using transfusion algorithms in VET has been shown to reduce overall cost of care in patients requiring transfusions most likely contributing to decreased length of stay.⁷

VET LIMITATIONS:

There are several limitations to VET testing in particular since they assess blood under low shear rate, as a result they are not sensitive to von Willebrand disease which requires high shear rate and collagen. Specific platelet receptor abnormalities are impacted due to the effect of thrombin on platelets and requires an assay modification called TEG platelet mapping. Additionally, testing DOACs require specialized reagents and testing.⁸

VETs have been widely used in pediatric patients, Pediatric results are limited and mostly extrapolated from adult ranges despite younger patients being shown to have shorter CT and increased clot kinetics and strength, but they are FDA approved only for adults.²

Studies that have compared VET analysis demonstrate that analyzers do not agree in particular when the results are outside the normal range. This confirms that each device needs it's own reference range and evaluation of relevant cut-off values and algorithms.²

CONCLUSION:

Without a doubt, VET is becoming part of patient management protocols in a variety of clinical settings. The method provides a rapid assessment of hemostasis in whole blood. Their use may drive better outcomes for patients and the blood supply, provided that VET interpretation is performed within the appropriate clinical context by informed medical personnel.

Institutions who utilize this method must ensure their analyzers are properly validated for their patient population. They should also be aware of the costs of testing as well as the savings due to improved transfusion practices. VET is here to stay!

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REFERENCES:

1. Volod, O, Salazar, E., Panelists on Viscoelastic and other coag assays, CAP today January 2024
2. Geoffrey D. Wool, Timothy Carll, Viscoelastic testing: Critical appraisal of new methodologies and current literature, International Journal of Laboratory Hematology 09 August 2023
3. Rita Selby, “TEG talk”: expanding clinical roles for thromboelastography and rotational thromboelastometry, Hematology Am Soc Hematol Educ Program (2020) 2020 (1): 67–75.
4. S Scarpelini 1, S G Rhind, B Nascimento, H Tien, P N Shek, H T Peng, H Huang, R Pinto, V Speers, M Reis, S B Rizoli, Normal range values for thromboelastography in healthy adult volunteers Braz J Med Biol Res 2009 Dec;42(12):1210-7.
5. Nicole H Leadbetter, Thomas B Givens, Francesco Viola Unique Approach to Quality Assurance in Viscoelastic Testing, The Journal of Applied Laboratory Medicine, Volume 5, Issue 6, November 2020, Pages 1228–1241, https://doi.org/10.1093/jalm/jfaa057
6. Newitt, VN., New Visco elastic testing requirement in checklist, CAP Today, September 2023.
7. Kuiper G, van Egmond LT, Henskens YMC, et al. Shifts of transfusion demand in cardiac surgery after implementation of rotational thromboelastometry-guided transfusion protocols: analysis of the HEROES-CS (HEmostasis registry of patiEntS in cardiac surgery) observational,
8. Oksana Volod, MD Is TEG the Right Assay Clinical Laboratory News, : MAY.1.2023

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