Thromboelastography for Hypocoagulable Patients with Non-Traumatic Bleeding

Author: Charles Cullison, DO and Romeo Fairley, MD (University of Texas at San Antonio, Emergency Medicine) // Reviewed by: Marina Boushra, MD; Alex Koyfman, MD (@EMHighAK); and Brit Long, MD (@long_brit)

Case:

A 47-year-old male with a past medical history significant for hypertension, diabetes and atrial fibrillation on rivaroxaban presents for nausea and vomiting. He has had nausea since this morning with three episodes of vomiting, with the last episode being a mixture of bright red blood and coffee-ground material. The patient is tachycardic but normotensive and oxygenating well on room air. His conjunctiva and nail beds are pink and his abdomen is benign. Examination of his emesis bag confirms the presence of coffee-ground particulates mixed with bright red blood.


Background:

The use of anticoagulant and antiplatelet agents is nearly ubiquitous in today’s medical landscape. While bleeding is a known side effect, the degree to which these medications may be directly contributing to an individual’s symptoms may be difficult to ascertain given the medications’ variable efficacy, half-lives, and patient compliance.

PT/INR and PTT are commonly obtained measures of coagulation in the emergency department. However, their utility is limited as they are simply a snapshot in time and do not characterize the interaction between procoagulant factors, anticoagulant factors, platelets and the fibrinolytic system.1 Additionally, there is a dose dependent drop in the sensitivity of INR and PTT with varying blood levels of direct oral anticoagulation(DOAC) therapy.2-These tests are also affected by the individual lab’s chosen reagent for the study.8 A thromboelastogram (TEG) is a study of a patient’s ability to form then break down clots. It provides a more dynamic picture of the patient’s ability to coagulate. While TEGs are commonly used to manage traumatic bleeding, until recently, this test has not been commonly used to manage patients with non-traumatic hemorrhage in the setting of anticoagulant or antiplatelet medication.

The process of obtaining and analyzing a TEG is discussed in detail later. In summary, a TEG involves obtaining a blood sample, spinning it in the lab, and watching it form and break down clots. The different phases of clot formation are recorded. If one phase is too long or too short, it directly correlates with dysfunction in a particular component of the plasma related to clot formation.9 This information can be used to assess and tailor dynamic resuscitative efforts in patients with bleeding, especially if they are on any anticoagulant or antiplatelet medications.

There have been multiple studies evaluating the use of TEG-guided resuscitation in patients in the setting of cardiothoracic surgery, liver transplant surgery, and trauma with favorable results.10,11 Numerous articles also show that TEG can be used to detect clotting defects in patients on anti-coagulation.12-17  The following article evaluating the utility of TEG in guiding the resuscitation on non-traumatic hemorrhage was recently published in the Journal of Hepatology and was then recognized by the New England Journal of Medicine as being practice-changing.


Article Name:

Kumar, M., Ahmad, J., Maiwall, R., Choudhury, A., Bajpai, M., Mitra, L. G., Saluja, V., Mohan Agarwal, P., Bihari, C., Shasthry, S. M., Jindal, A., Bhardwaj, A., Kumar, G., & Sarin, S. K. (2020). Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial. Hepatology (Baltimore, Md.), 71(1), 235–246. https://doi.org/10.1002/hep.30794

Study Design:

This is a single-center, randomized controlled trial comparing the use of TEG versus standard of care (SOC) in the treatment of cirrhotic patients with non-traumatic, non-variceal upper GI bleeding. 96 patients were enrolled in the study. Inclusion criteria were: 1) patients with advanced liver cirrhosis of any etiology; 2) age 18-80 years; 3) bleeding from a non-variceal source confirmed by endoscopy; 4) INR > 1.8, platelets < 50× 109/L. Exclusion criteria were: 1) patients with variceal bleeding; 2) patients with current or previous thrombotic events; 3) patients currently on anti-coagulant therapy; 4) recent hemodialysis; 4) pregnancy; 5) significant cardiopulmonary disease.

Patients in the TEG group received blood products using the following triggers: FFP at a dose of 10 mL/kg of ideal body weight (IBW) when reaction time (R time) was greater than 10 minutes; a single-donor apheresis platelet (SDAP) unit, which corresponds to approximately 6 to 8 pooled units of platelets, transfused when the maximum amplitude (MA) was less than 55 mm; and cryoprecipitate (5 pooled units) transfused when the alpha angle was less than 45°.

In the SOC group, patients received FFP at the dose of 10 mL/kg IBW when the INR was greater than 1.8 and/or received platelets in the amount of 1 SDAP when the platelet count was below 50× 109/L.

Outcomes:

The study’s primary outcome was the volume of FFP transfused in milliliters. Secondary outcomes included:  (1) 5-day treatment failure (i.e., failure to control bleeding); (2) failure to control re-bleeding after 5 days; (3) amount of platelets and cryoprecipitate transfused; (4) serious transfusion-related reactions (cardiopulmonary involvement, hemolytic, sepsis, hypotension and anaphylactic reactions); (5) duration of intensive care unit (ICU) and hospital stay; (6) survival at 6 weeks.

Results:

Compared to the SOC group, the TEG group required half the total volume of FFP transfused, were less likely to require transfusion of all three blood components (27% vs. 87%), and were more likely to require no transfusions (14% vs. 0%; P<0.02 for all comparisons). Serious transfusion reactions occurred significantly less often in the TEG group (31% vs.  75%). Transfusion-related acute lung injury (TRALI) developed in 6/49 patients (12.2%) vs 23/27 patients (48.9%). Failure to control bleeding, length of hospital stay, and survival were not significantly different between groups.

Strengths:

1) In the SOC group, transfusion criteria matched routine emergency departments criteria, giving FFP for INR greater than 1.8 or platelets for a platelet count less than 50 x109/L.

2) The two groups had no statistical differences when comparing age, sex, clinical features, cirrhosis prognostic scores, and clotting parameters.

3) The use of TEG allowed some patients to receive no blood products while all patients in the SOC group received blood products and their outcomes were not significantly different.

Limitations:

1) “Significant” cardiopulmonary diseases that excluded patients from participation in the study are not defined.

2) FFP volume was the primary outcome and they did not comment about RBC use, which is a large factor in resuscitative efforts for bleeding patients in the emergency department.

3) Samples obtained from patients that were actively bleeding were allowed 30-40 minutes for the test to run and they allowed up to one hour before the test could even be started. This delay in treatment efforts would not be feasible in the unstable bleeding patient in the emergency department.

4) The sample size is small, limiting generalizability.

5) Both study groups had high rates of failure to control bleeding (22.4% and 29.8% respectively).

6) Both groups had high rates of re-bleeding after 5 days (50% and 57.6%respectively).

7) Their were a number of deaths in each treatment group and they were counted toward a secondary outcome for mortality at 6 weeks but they did not comment on the They do not comment on the cause of deaths in either of the study groups.

8) This study excluded patients who were on anti-platelet and anti-coagulation therapy, which are common in bleeding patients in the emergency department.


TEG Guide:

TEG is a point-of-care, global hemostasis assessment procedure that measures the viscoelastic changes that occur during the hemostatic process, providing real-time reports.

TEG studies are broken down into different segments of the coagulation process:  R time, K time, Max Amplitude, and LY (Figures 1 and 2). The following represents a convenient but simplified view on disturbances of the coagulation process. It is important to remember that due to the complex nature of hemostasis these TEG parameters are interrelated.

1.) Prolongation of the R time reflects a quantitative or qualitative deficiency of coagulation factors

  • Correct with fresh frozen plasma (FFP) transfusion, prothrombin complex, or anticoagulant reversal.

2.) Prolongation of the K time, or a decrease of the alpha angle, suggests a deficiency of fibrinogen

  • Correct with cryoprecipitate or fibrinogen concentrate.

3.) Low MA indicates a quantitative or functional deficiency of platelets.

  • Correct with platelet transfusion or DDAVP.

4.) Increased LY value represents an activated fibrinolysis

  • Treat with aminocaproic or tranexamic acid.

5.) If the TEG reveals the opposite of the above it suggests a prothrombotic state.

Discussion and Conclusions:

TEG has been extensively studied in trauma and surgical patients, but has not been well studied in nontraumatic bleeding, nor has its use been well evaluated in the emergency department. This study suggests that patients with nontraumatic hemorrhage may benefit from TEG-guided resuscitation and do not always need rapid transfusion of blood products. This can limit transfusion-related risks for susceptible populations. It also allows for the conservation of valuable resources through data-driven allocation of blood products to patients who are most likely to benefit from them. TEG-guided resuscitation may be difficult in the emergency department due to concern for treatment delays but obtaining TEGs early in the hospital course may assist the admitting team’s work-up and treatment.


Clinical Take Home Points:

  1. TEG can be a useful tool to assist in the treatment of patients presenting with nontraumatic bleeding who are hypo-coagulable.
  2. The use of TEG allows for the minimization of serious transfusion reactions by guiding the amount of transfusions a patient truly needs for optimal outcome.
  3. Before ordering a TEG, the provider should know which reagents are used in the study. Kaolin-activated TEG assays, such as the one used in the study discussed, have higher false negative rates in patients who are anti-coagulated with warfarin.20
  4. If patients have bleeding and are unstable, start resuscitation with the ABCs. Even though TEG aids in the allocation of blood product resources, it does not help in stabilizing unstable patients and care should not be delayed to obtain a TEG.
  5. This study only used TEG in patients with hypocoagulability due to advanced cirrhosis. It did not study the use of TEG in patients on anti-coagulation.
  6. More research is needed to evaluate the usefulness in the emergency department on patients presenting with nontraumatic bleeding on anticoagulation.

Further Reading:

Previous Articles From emDOCs:

http://www.emdocs.net/thromboelastogram-teg-five-minute-primer-emergency-physician/

References:

  1. Stettler, G. R., Moore, E. E., Moore, H. B., Nunns, G. R., Coleman, J. R., Colvis, A., Ghasabyan, A., Cohen, M. J., Silliman, C. C., Banerjee, A., & Sauaia, A. (2019). Variability in international normalized ratio and activated partial thromboplastin time after injury are not explained by coagulation factor deficits. The journal of trauma and acute care surgery, 87(3), 582–589. https://doi.org/10.1097/TA.0000000000002385
  2. 2. Van Ryn J, Stangier J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A. Dabigatran etexilate – a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 2010; 103: 1116–27.
  3. Samama MM, Martinoli JL, LeFlem L, Guinet C, Plu‐Bureau G, Depasse F, Perzborn E. Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103: 815–25.
  4. Dale BJ, Ginsberg JS, Johnston M, Hirsh J, Weitz JI, Eikelboom JW. Comparison of the effects of apixaban and rivaroxaban on prothrombin and activated partial thromboplastin times using various reagents. J Thromb Haemost 2014; 12: 1810–15.
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  6. Hillarp A, Gustafsson KM, Faxälv L, Strandberg K, Baghaei F, Fagerberg Blixter I, Berndtsson M, Lindahl TL. Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti‐FXa assays. J Thromb Haemost 2014; 12: 1545–53.
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  9. Shaydakov ME, Blebea J. Thromboelastography (TEG) [Updated 2020 Feb 20]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537061/
  10. Coleman, J. R., Moore, E. E., Chapman, M. P., Banerjee, A., Silliman, C. C., Ghasabyan, A., Chandler, J., Samuels, J. M., & Sauaia, A. (2018). Rapid TEG efficiently guides hemostatic resuscitation in trauma patients.164(3), 489–493. https://doi.org/10.1016/j.surg.2018.04.029
  11. De Pietri, L., Bianchini, M., Montalti, R., De Maria, N., Di Maira, T., Begliomini, B., Gerunda, G. E., di Benedetto, F., Garcia-Tsao, G., & Villa, E. (2016). Thrombelastography-guided blood product use before invasive procedures in cirrhosis with severe coagulopathy: A randomized, controlled trial. Hepatology (Baltimore, Md.), 63(2), 566–573. https://doi.org/10.1002/hep.28148
  12. Wang, S. C., Shieh, J. F., Chang, K. Y., Chu, Y. C., Liu, C. S., Loong, C. C., Chan, K. H., Mandell, S., & Tsou, M. Y. (2010). Thromboelastography-guided transfusion decreases intraoperative blood transfusion during orthotopic liver transplantation: randomized clinical trial. Transplantationproceedings,42(7),2590–2593.https://doi.org/10.1016/j.transproceed.2010.05.144
  13. Artang R, Anderson M, Nielsen JD. Fully automated thromboelastograph TEG 6s to measure anticoagulant effects of direct oral anticoagulants in healthy male volunteers. Res Pract Thromb Haemost. 2019;3(3):391–396. Published 2019 May 12. doi:10.1002/rth2.12206
  14. Stettler GR, Moore EE, Moore HB, et al. Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion. Surgery. 2017;162(6):1286–1294. doi:10.1016/j.surg.2017.07.022
  15. Artang R, Anderson M, Nielsen JD. Fully automated thromboelastograph TEG 6s to measure anticoagulant effects of direct oral anticoagulants in healthy male volunteers. Res Pract Thromb Haemost. 2019;3(3):391–396. Published 2019 May 12. doi:10.1002/rth2.12206
  16. Stettler GR, Moore EE, Moore HB, et al. Platelet adenosine diphosphate receptor inhibition provides no advantage in predicting need for platelet transfusion or massive transfusion. Surgery. 2017;162(6):1286–1294. doi:10.1016/j.surg.2017.07.022
  17. Bowry R, Fraser S, Archeval-Lao JM, et al. Thrombelastography detects the anticoagulant effect of rivaroxaban in patient with stroke. Stroke. 2014 ; 45 (3) : 880883 .doi: 10.1161/STROKEAHA.113.004016
  18. Figure 1: Graph of the Different Phases of Thromboelastography. Adapted from teg.haemonetics. By Haemonetics.https://teg.haemonetics.com/en-gb
  19. Semon G, Cheatham M. Thromboelastography in Trauma. Surgical Critical Care Evidence-Based Guidelines Committee. 2014. www.surgicalcriticalcare.net/Guidelines/TEG%202014.pdf
  20. Dunham, C.M., Rabel, C., Hileman, B.M. et al. TEG® and RapidTEG® are unreliable for detecting warfarin-coagulopathy: a prospective cohort study. Thrombosis J 12, 4 (2014). https://doi.org/10.1186/1477-9560-12-4

 

Previous Articles From EMDOCS:

http://www.emdocs.net/thromboelastogram-teg-five-minute-primer-emergency-physician/

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