Meeting thromboelastometry clinical needs and new quality standards

Since it was first described in 1948 by Hartert in Heidelberg, Germany,¹ “thrombelastographie,” a method of measuring the viscoelastic properties of a blood clot during its formation, has evolved significantly. In the early 1990s a modified thromboelastography system was developed in Munich, Germany. Later termed “rotational thromboelastometry” or “RoTEM,” the test was made simpler to operate and to interpret, which allowed the device to be used in a broader range of clinical settings. The testing could now be performed more easily by clinicians in a central or decentralized laboratory setting and remotely deliver results more rapidly and reliably to the point-of-care location. These results, in conjunction with other laboratory assays, can be helpful for guiding therapeutic intervention during acute bleeding events.

Benefits of thromboelastometry

The benefits of implementing thromboelastometry for the management of perioperative bleeding are multiple. Diagnostic performance, safety, efficacy, and cost-effectiveness have all been shown to be improved by using a goal-directed therapy that includes thromboelastometry-guided protocols as opposed to conventional laboratory testing alone. These benefits were previously described in detail in MLO² and in several other publications^3-5

Thromboelastometry, in combination with other laboratory assays, improves diagnostic performance by delivering additional information more quickly and therefore can help guide therapeutic intervention more quickly. According to Haas et al, the turnaround time of thromboelastometry results is significantly shorter (15 to 20 minutes) than that of conventional laboratory results (45 to 60 minutes).⁶ Since the remote display provides visualization of real-time clot development, clinicians can then assess the different phases of clot development as they occur and treat deficiencies accordingly. Rapid assessment of clot initiation, propagation rate, and clot firmness is critical to determine appropriate treatment of severe bleeding and can be delivered to any point-of-care location regardless of where the actual testing is performed. Using well designed algorithms that are guided by thromboelastometry has been shown to be clinically efficacious and can increase patient safety and improve outcomes.^7-9 Thromboelastometric measurements have been shown to be predictive of the need for massive transfusion,¹⁰ and protocols that include thromboelastometry-guided therapy can help prevent massive transfusion. Likewise, these protocols can help improve patient outcomes by guiding hemostatic therapy and avoiding unnecessary transfusions as well as the deleterious effects of allogeneic blood transfusions.^8,9 Thromboelastometric analysis and guided therapy has also been shown to be able to predict and help prevent thromboembolic events.^7,8

The ability of thromboelastometry to predict bleeding and risk of thrombosis and confirm hyperfibrinolysis and the need for activating a massive transfusion protocol (MTP) allows for faster intervention. Therefore, protocols that include thromboelastometry can then aid by stopping microvascular bleeding quickly and avoiding massive transfusion and thrombosis at the same time.^7-9

The financial benefit that an established bleeding management program can provide to a hospital system can be significant. Thromboelastometry has been shown to be an important tool to reduce the primary costs of blood products within hospitals.^7,8,11-15 In addition to primary acquisition costs of the blood products, activity-based costs of blood transfusion and secondary costs of complications related to allogeneic blood transfusion have to be considered.^9,16,17 Thromboelastometry has also been shown to reduce the incidence of transfusion-related adverse events8 and accordingly may reduce corresponding hospital costs. Reducing these secondary costs of blood may even exceed the cost-savings for blood transfusion requirements themselves and improve patients’ clinical outcomes.

It is important to note that the results from thromboelastometric analysis should not be the sole basis for a patient diagnosis and treatment. These results should be considered along with a clinical assessment of the patient’s condition and other coagulation laboratory tests.

Evidence and recommendations

A recent search revealed well over 1,000 publications on thromboelastometry and showed a broad range of clinical and research applications. The main body of evidence involves publications on research and application in the traditional clinical settings of cardiac surgery, liver transplantation, and trauma. There is, however, an increasing interest in researching and applying thromboelastometry in the areas of OB hemorrhage, neurosurgery, spine surgery, and critical care medicine, and we now better understand the coagulopathies common in these settings. As such, physicians are increasingly using thromboelastography (TEG) and ROTEM-guided protocols to help manage hemostatic derangement outside of the traditional areas.

Guided protocols that include thromboelastometry testing are moving closer to becoming the standard of care for bleeding management in the United States. The European Society of Anesthesiology has already given its grade of strong recommendation based on solid evidence that thromboelastometry should be included in perioperative bleeding management protocols since 2013.¹⁸ In 2015, the American Society of Anesthesiology published an update to practice guidelines for perioperative bleeding management¹⁹ which included recommendations for the use of bleeding algorithms, goal-directed therapy, and the use of TEG or ROTEM when available. Also, in 2015, The American College of Surgeons published specific guidelines for the use of TEG or ROTEM for massive transfusion protocol management.²⁰

Meeting the new quality standard: IQCP

Prior to Individualized Quality Control Plan (IQCP) adoption, Equivalent Quality Control (EQC), QSA.02.04.01,²¹ was the available option when determining the required frequency of external controls. As of 2003, a reduced frequency of external QC was allowed if the instrument’s design included internal monitors. As an example, the integrated system function checks monitor the optical and electromechanical components of the ROTEM device and, therefore, it qualified for EQC option 2. Without such features, under CFR,42, Section 493.1269,²² a lab had to test two levels of external QC each day a non-waived test was run, and coagulation tests fell under even a more stringent criterion, requiring QC every eight hours of patient testing. Regardless, EQC remained controversial. Thus, laboratory professionals, along with government officials and industry, joined to determine the best patient-focused approach to QC. The outcome was IQCP. Prior to full adoption, laboratories were allowed to continue with EQC, option 2, a full two years before the mandated IQCP deadline of Jan. 1, 2016. This grace period provided professionals an opportunity to evaluate IQCP and the widely accepted Clinical Laboratory Standards Institute (CLSI) standard, EP 23.

IQCP: The new standard

To facilitate IQCP implementation, CLSI developed a risk-based method for determining QC procedures and frequency, CLSI EP 23,²³ Laboratory Quality Control Based on Risk Management. IQCP is designed to assess hazards and failure modes, evaluate those risks, and identify the control mechanisms that mitigate those risks. Fortunately, the clinical laboratory was already practicing many components of IQCP, but assimilating all the quality parts had not been required prior to Jan. 1, 2016.

While IQCP is mandated for a broad range of in vitro diagnostic devices and assays, each device from a particular manufacturer has unique features as part of its integrated quality system. Because of this, these authors have the expertise to describe the specific features of the ROTEM device that allow for implementation into a laboratory’s IQCP program.

The developer of the ROTEM evaluated the instrument design against the CLSI EP 23 standard. The evaluation resulted in a full risk assessment template which is provided to users developing their ROTEM-specific IQCP.

The Risk Assessment outline of the ROTEM device includes all phases of testing: pre-analytic, analytic, and post-analytic. Within each phase the following aspects of risks are evaluated:

• Specimen Integrity/Acceptability
• Environmental Impact
• Reagent and QC Stability/Integrity
• Function of Test System
• Testing personnel Training and Competency

Furthermore, the QC Plan includes practices, resources, and procedures that control the quality of the test process. The reliability and accuracy of tests result in a patient-focused approach to QC. The IQCP template for the ROTEM is a synopsis of the engineering, internal, and procedural control features, submitted as recommendations to consider during the risk assessment period. The device’s design lends itself to offset risk using a simple 3 factor approach formula, Risk (SEV*OCC *(2-DET), supported by Westgard JO. Six Sigma Risk Analysis.²⁴ This quantitative method focuses on defect rates and estimation of the number of potentially impacted patient results, using a scale of 0-2.

The lab determines the severity of harm and the estimated occurrence rates. A high score of “2” in each category is easily offset by detectability. Since the software and hardware of the device integrate many mitigating risk features, users achieve an overall low score and can choose to continue a weekly external/liquid QC scheme after the 30-day QC evaluation. They also can create Quality Control Plans (QCPs) in order to measure unacceptable risks. Control mechanisms are implemented to mitigate failure modes while simultaneously determining the acceptable level of risk reduction. The goal is to ensure accuracy and reliability in patient testing. Examples include:

• Control(s): Type, number, and frequency
• Criteria for acceptable QC results, e.g., electronic and procedural controls as well as training and competency assessments.

Finally, once the IQCP’s initial risk assessment and QCP are complete, labs implement an ongoing monitoring protocol. Ultimately, the lab must determine if the IQCP is working to mitigate risk or not. In doing so, each lab integrates its skill sets and device knowledge. The ROTEM device offers an IQCP solution that facilitates IQCP structure while continuing to address the Quality Control Plan and ongoing Quality Assessments required by accrediting agencies.

REFERENCES

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   Untersuchungsverfahren. Klinische Wochenschrift. 1948;26(37/38):577-583.
2. Allen T. Thromboelastometry: Its method, application and benefits. MLO. 2014;46(2):26-29.
3. Tanaka, KA, [Please provide two more authors] et al. Rotational thromboelastometry ( ROTEM)-based coagulation management in cardias surgery and major trauma. J. Cardiothorac. Vasc. Anesth. 2012;26(6):1083-93.
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22. CFR, Title 42, Chapter IV, Subchapter G, Part 493, Subpart K, Section 493.1269 (d)(3).
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Todd W. Allen serves as Director of Clinical Application & Business Development for TEM Systems, Inc., which markets and sells the ROTEM delta Hemostasis Monitoring
System in the U.S; manufactured by TEM International, GmbH, Munich, Germany.

Kimberly Sheldahl serves as Director of Clinical and Technical Support for TEM Systems, Inc.