|Year : 2022 | Volume
| Issue : 5 | Page : 7-10
Point-of-care thromboelastography, rotational thromboelastometry during extracorporeal membrane oxygenation
Abdullah M Abudayah
Department of Intensive Care Service, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
|Date of Submission||01-Nov-2022|
|Date of Decision||29-Nov-2022|
|Date of Acceptance||15-Dec-2022|
|Date of Web Publication||04-Feb-2023|
Abdullah M Abudayah
Department of Intensive Care Service, Prince Sultan Military Medical City, Riyadh
Source of Support: None, Conflict of Interest: None
Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. The patients requiring ECMO are at increased risk of developing significant coagulopathy. The exposure of a patient's blood to the artificial surface of the ECMO circuit results in the activation of the coagulation-fibrinolysis system and an inflammatory response. During ECMO, anticoagulation is required to prevent thrombotic complications, and unfractionated heparin (UFH) remains the predominant anticoagulation agent used to minimize the potentially life-threatening complications related to bleeding events or thromboembolic complications. Most centers adjust UFH by activated clotting time (ACT) of 140–180 sec or partial thromboplastin time (PTT) of 40–80 s. In this article, we will review thromboelastometry use during ECMO in ICU.
Keywords: Anticoagulation, extracorporeal membrane oxygenation, point-of-care anticoagulation
|How to cite this article:|
Abudayah AM. Point-of-care thromboelastography, rotational thromboelastometry during extracorporeal membrane oxygenation. Saudi Crit Care J 2022;6, Suppl S1:7-10
|How to cite this URL:|
Abudayah AM. Point-of-care thromboelastography, rotational thromboelastometry during extracorporeal membrane oxygenation. Saudi Crit Care J [serial online] 2022 [cited 2023 Mar 22];6, Suppl S1:7-10. Available from: https://www.sccj-sa.org/text.asp?2022/6/5/7/369159
| Introduction|| |
Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. The patients requiring ECMO are at increased risk of developing significant coagulopathy. The exposure of a patient's blood to the artificial surface of the ECMO circuit results in the activation of the coagulation-fibrinolysis system and an inflammatory response. Coagulation and inflammation are also closely linked through networks of both humoral and cellular components, which might lead to disseminated intravascular coagulation. During ECMO, anticoagulation is required to prevent thrombotic complications, and unfractionated heparin (UFH) remains the predominant anticoagulation agent used to minimize the potentially life-threatening complications related to bleeding events or thromboembolic complications. Most centers adjust UFH by activated clotting time (ACT) of 140–180 sec or partial thromboplastin time (PTT) of 40–80 s.
Of course, the ACT is more commonly used because it is a bedside diagnostic test. PTT needs to be done in the laboratory. Moreover, the selection and schedule of diagnostic tests, including platelet count, antithrombin, ACT, activated partial thromboplastin time (aPTT), anti-factor Xa (anti-Xa), prothrombin time, and international normalized ratio must be carefully considered. Maintaining an appropriate balance between preventing thrombosis and the risk of bleeding is challenging because standard diagnostic tests are only partially functional measures of hemostasis. Although coagulation tests are routinely used to guide anticoagulation, they do not always accurately predict the risk for thrombosis or bleeding.
Patients on ECMO exhibit a range of hemostatic changes, including consumption of coagulation factors, thrombocytopenia, altered von Willebrand factor multimers, platelet dysfunction, and reductions in anti-thrombin levels.
Significant bleeding events occur in more than 30% of patients on ECMO, and better anticoagulation control may improve patient outcomes. Thrombotic complications occur in up to 8%–17% of patients on ECMO. Both bleeding and thrombotic complications are associated with increased mortality.,,
| The Activated Clotting Time|| |
The ACT is a whole blood test used to measure the anticoagulant effect of heparin; the ACT will be done bed site and give us immediate results and adjustment of the UFH. An ACT range of 180–200 s has been recommended for ECMO. However, the result is not always reliable because of multiple factors which can prolong the ACT independent of the UFH dose, including hemodilution, platelet function and number, hypothermia, hypofibrinogenemia, and coagulation factor deficiencies.
| The Activated Partial Thromboplastin Time|| |
The aPTT test is a plasma-based assay of clot formation used to monitor UFH. The therapeutic ranges for ECMO are 60–80 s in the setting of a standard bleeding risk versus targets of 40–60 s in patients at an increased bleeding risk.
The aPTT is a laboratory test and will not be done on-site, and in some diseases, the result needs to be more accurate. Furthermore, in some instances, the target level is not achieved, or if the level exceeds the 80 s, it is a risk of bleeding or thrombosis. Previous studies found little or no correlation between ACT and heparin dose, a moderate correlation between aPTT and heparin amount, and a weak correlation between ACT and aPTT. ACT might be an unreliable tool to monitor UFH during extracorporeal life support (ECLS) in adults.
Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) are viscoelastic tests of hemostasis in whole blood that has been used to monitor anticoagulation with ECMO. TEG can be done with or without an agent that inactivates heparin, so the anticoagulant effect of heparin can be separated from other factors. TEG can be done at the bedside on fresh blood or in the laboratory in calcium-free blood (adding calcium to the activator).
TEG®/ROTEM parameters inform time to initial fibrin formation, cross-linking of fibrin, clot firmness, platelet function, and fibrinolysis. Paired TEG®/ROTEM samples with and without adding heparinase allow for the underlying assessment of hemostasis in the presence of UFH. As a result, UFH responsiveness can be evaluated with TEG®/ROTEM by examining the difference in R or clotting time between tests with and without heparinase, which may be beneficial when there is a concern for heparin resistance.
In a series of 27 pediatric ECLS patients, TEG® measurements were performed alongside ACT and aPTT. In 171 paired results, aPTT correlated with all TEG® parameters (R time, K time, and α angle), but given that they both measure time to initial fibrin formation, the strongest correlation was between aPTT and TEG® R time (r = 0.31).
In contrast, ACT correlated weakly with all TEG® parameters. Similar results have been published comparing ROTEM with conventional coagulation tests.
Regarding patients supported on ECMO, multiple studies have evaluated the safety and feasibility of a TEG-driven strategy to titrate heparin versus the “conventional” approach based on aPTT monitoring, with a trend toward improvement in adverse outcomes. For example, a recent multicenter, randomized, controlled trial was performed involving adult patients with acute respiratory failure treated with venovenous ECMO who were randomized to manage heparin anticoagulation using either a TEG-based protocol (target 16–24 min of the R parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5–2 of aPTT ratio, aPTT group). While underpowered to detect statistically significant differences between the groups (n = 42), patients in the aPTT group tended to bleed more compared to the TEG group (15 vs. 10, P = 0.21). In addition, heparin dosing was lower in the TEG group compared to the aPTT group (12 IU/kg/h vs. 16 IU/kg/h, respectively, P = 0.03), with no increase in thrombotic complications. While a larger trial is needed, the results indicate that a TEG-driven protocol is safe and feasible in adult patients requiring venovenous (VV) ECMO. In a recent pediatric study, a retrospective chart review of patients requiring VV and venoarterial ECMO was performed within a single-center, tertiary-care children's hospital. The study evaluated optimal values for citrated kaolin TEG R time and anti-Xa activity that would minimize both bleeding and thrombotic complications in pediatric and neonatal patients. The study concluded that an anti-Xa activity greater than 0.25 IU/mL (sensitivity 81%, specificity 67%, positive predictive value [PPV] 81%, and negative predictive value [NPV] 58%) and a TEG R time greater than 17.85 min (sensitivity 84%, specificity 68%, PPV 82%, and NPV 59%) might minimize the risk of thrombosis in pediatric and neonatal ECMO patients. An optimal target to reduce the risk of bleeding events could not be identified in this study.
To date, there is a belief that optimal anticoagulation, including the indications for antithrombin supplementation, relies on a comprehensive and standardized evaluation of multiple measures of hemostasis, including aPTT, ant-Xa, TEG®, Activated Thrombine (AT) activity, platelet count, and fibrinogen concentration. Anticoagulation should be titrated based on the overall hemostatic state of the patient, as evidenced by laboratory evaluation. It should be put in context with the clinical hemostatic condition of the patient and their unique risk of bleeding or thrombotic complications.
Interpretation of the thromboelastography test
R-time (reaction) (5–10 min)
- Time of latency from the start of the test to initial fibrin formation (amplitude of 2 mm)
- Initiation phase
- Dependent on clotting factors.
If prolonged R (clotting factors/anticoagulation).
Treatment: Fresh frozen plasma and reverse anticoagulation.
K-kinetics (1–3 min)
- Time is taken to achieve a certain level of clot strength (amplitude of 20 mm)
- Amplification phase
- Dependent on fibrinogen.
If K increased, give Cryo.
Angle (slope of the line between R and K) (50°–70°)
- Measures the speed at which fibrin build-up and cross-linking take place, hence assesses the rate of clot formation
- “Thrombin burst”/propagation phase
- Dependent on fibrinogen.
If decrease the angle give, Cryo.
- Represents the ultimate strength of the fibrin clot, i.e., the overall stability of the clot
- Dependent on platelets (80%) and fibrin (20%) interacting via GPIIb/IIIa
If maximal amplitude (MA) decreases, give platelets and Desmopressin.
A30 or LY30 = Amplitude at 30 min
- Percentage decrease in amplitude at 30 min post-MA [Figure 1]
- Fibrinolysis phase.
|Figure 1: Normal result TEG test shows all different phases. TMA: Time to maximum amplitude, CLT: Clot lysis time, R: Time reaction, K: Kinetics, MA: Maximal amplitude, A30, or LY30: Amplitude at 30 min|
Click here to view
| Conclusion|| |
TEG is one of the diagnostic tests to measure the effect of the UFH, providing more information than the ACT. No available data in the literature necessitate a deviation from current practice and the recommendation of multiple laboratory tests, including but not limited to anti-Xa, TEG/ROTEM, PTT, and AT levels.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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