In this post, we’ll discuss viscoelastic hemostatic assays (VHAs), namely ROTEM (Rotational Thromboelastometry), and how we can use this tool to enhance the care of traumatically injured patients. This is the first in a two-part series. This part reviews the Evidence for VHAs in Trauma, while Part 2, found here, reviews the practical aspects of using ROTEM in trauma.
Hemorrhage remains the leading cause of preventable death from trauma. What if I told you there was a test that reduced transfusion requirement through goal-directed care, is already used at multiple Canadian, US, and European trauma centers, and has possible mortality benefit in bleeding patients?
ROTEM (rotational thromboelastometry) provides goal-directed transfusions for individual patients during damage control and hemostatic resuscitation, adding timely laboratory data to our clinical impression. In Canada, more and more centres are adopting ROTEM for the resuscitation of critically ill bleeding patients. In the US, TEG (thromboelastography) and ROTEM have been used for many years to guide massive transfusion. In Europe, it is standard of care to use VHAs (viscoelastic hemostatic assays; i.e. ROTEM or TEG) to guide trauma resuscitations.
For the purpose of this post we will focus on ROTEM as this is predominantly used in Canada. Information on TEG can be found from multiple other FOAM sources (found below).
This post will frame the discussion around ROTEM by answering 4 questions:
- What do we do right now?
- What tests are available now, how good are they, and the idea behind ROTEM
- Why should we use ROTEM?
- We’ll cover the many advantages of ROTEM-guided resuscitation
- How do I use ROTEM to guide management?
- How to read a ROTEM output and how it guides transfusion
- Why don’t we already have ROTEM?
- Important but solvable barriers to implementation
Before we get into the meat of the post: if this test is so great and everybody’s using it already… what do the guidelines say?
TL/DR; Use it if you have it.
- The European guideline on the management of major bleeding and coagulopathy following trauma. 2019
- Recommend coagulation monitoring with traditional lab tests or VHAs (Grade 1C).
- Resuscitation measures should be continued using a goal-directed strategy, guided by standard laboratory coagulation values and/or VHAs. (Grade 1B)
- British Society for Haematology. Guideline for VHAs in the management of major bleeding. 2018
- Normal VHA results confer a high NPV for transfusion need, enabling close monitoring without immediate MTP activation of the major haemorrhage protocol. Grade 2B.
- VHAs, particularly TEG, may reduce mortality and reduce transfusion exposure and, if available, may be considered for transfusion guidance in trauma haemorrhage. Grade 2B.
- European Society of Anesthesiology guideline for Management of severe perioperative bleeding. 2017
- Recommend algorithms incorporating triggers and targets based on VHA coagulation monitoring to guide individualized hemostatic intervention in the case of perioperative bleeding. (Grade 1C)
- Practice Guidelines for perioperative blood management. ASA task force on perioperative blood management. 2015
- If coagulopathy is suspected, obtain standard coagulation tests (g., INR, aPTT, fibrinogen concentration) or viscoelastic assays (e.g., thromboelastography [TEG] and ROTEM), if available, as well as platelet count
- Both the consultants and ASA members agree that if coagulopathy is suspected, obtain viscoelastic assays (g., TEG and ROTEM), when available, as well as platelet count
- Massive transfusion policies at trauma centers participating in the ACS TQIP. 2015
- (Massive transfusion in Trauma Guidelines. ACS TQIP. 2014.)
- Goal-directed therapy based on: Standard laboratory coagulation values, and/or VHAs, if available. Once laboratory data are available, resuscitation should be goal directed based on the laboratory findings and clinical evidence of ongoing bleeding
- VHAs as the standard for transfusion or injection of blood plasma, cryoprecipitate, platelet concentrate, or anti-fibrinolytic agents in the treatment strategy for traumatic coagulopathy and hemorrhagic shock
Background: What do we do right now?
The Clotting Cascade
A brief review of the clotting cascade (…I know, I’m sorry): the goal and end result is a platelet plug reinforced by cross-linked fibrin chains.
- Enzymatic phase: requires coagulation factors
- Platelet phase: thrombin generation on activated platelets generate fibrin from fibrinogen which crosslinks building the clot
- Fibrinolytic phase: clot dissolution is dependent on fibrin and tPA from endothelial cells
The clotting cascade can be “measured” by standard lab tests (SLTs):
- Local tissue effects – no clinically usable way to assess
- Intrinsic (F8, 9, 11, 12) – PTT
- Extrinsic (TF, F7) – PT/INR
- Common pathway (FXa, thrombin, fibrinogen) – TT, fibrinogen
- Platelet portion: CBC (platelet count)
- Fibrinolytic phase: d-dimer
The issues with SLTs are:
- Originally designed for monitoring therapeutic anticoagulation, not expeditious identification of trauma-related coagulation defects
- Not ideal to predict risk of bleed or clotting ability as these tests are run with plasma alone, not accounting for cellular clotting components (i.e. lack of in vivo applicability)
- And they have: longer turnover time, lack of specificity, and lack of ability to guide transfusion of blood products acutely
Acute Trauma Coagulopathy
- Hemorrhagic shock secondary to trauma is associated with intrinsic coagulopathy beyond the lethal triad, termed acute trauma coagulopathy (ATC) or trauma-induced coagulopathy (TIC)
- In severely injured patients, 25-35% already have a trauma-induced coagulopathy at presentation to ED
- This coagulopathy poses 8x higher risk of death from trauma
- ATC occurs early after injury, independent of coagulopathy from acidosis, hypothermia, or hemodilution and factor dilution
- Hypoperfusion is a large determinant of coagulopathy
- Hyperfibrinolysis: Injured endothelium releases tPA leading to early breakdown of necessary clot, therefore, increased need for blood products
- Fibrinolytic shutdown: not all trauma patients are coagulopathic, some can be hypercoagulable, reducing transfusion requirements
- Trauma patients are at high risk of hemorrhage-related morbidity and mortality, and ATC further increases the risk of complications, need for transfusion, and length of stay
Balanced 1:1:1 transfusion strategies have been found to improve mortality in this population but given the unique nature of each patient’s coagulopathy, is this one-size-fits-all approach appropriate for everyone? Is Balanced transfusion enough?
What is ROTEM?
ROTEM measures clot formation over time. It is a dynamic assessment of clot formation, strength, stability, and dissolution. It measures the global viscoelastic properties of whole blood clot formation.
- A small sample of patient blood is placed into a cup
- A sensor rod is inserted into the blood sample
- The rod is then gently rotated, with a subsequent clot forming between the cup and rod
- As blood clots form and strengthen, they exhibit increasing viscosity and elasticity
- This leads to increased resistance on the pin’s rotation
- This is converted to electrical signals to create 2D graphical/numerical output
- In ROTEM, the pin rotates. In TEG, the cup rotates.
- There are multiple parallel channels that test different aspects of clotting using different reagents, but for our purposes, we will focus on EXTEM and FIBTEM
What are the Advantages of ROTEM?
- Point-of-care test – first results 5-10min, full results 30min
- Results are displayed in both graphical and numerical format with reference ranges
- Assessment of global hemostatic potential (whole blood, not just plasma and fibrin formation)
- Detects specific portion of clotting that’s disrupted
- Detect specific defects in coagulation
- e. hypofibrinogenemia, hyperfibrinolysis, factor deficiency, heparin effect
- Can assess hyperfibrinolysis
- This is unique to VHAs over SLTs; No SLT to assess hyperfibrinolysis
- This is an important aspect of ATC as it has been associated with increased transfusion requirements and mortality
- Can perform at multiple temperatures
- Therefore: rapid diagnosis of specific coagulopathies, suggesting specific treatments which may reduce transfusion requirement, decrease hemorrhage, and decrease mortality…?
Goal-directed Hemostatic Resuscitation
- ROTEM correlates with SLTs, assesses TIC/ATC, and predicts massive transfusion, need for transfusion, fibrinolysis, and coagulopathy-related mortality
- Numerous studies verifying the above, looking at different aspects of ROTEM/TEG with different measurements and cut-offs which are the basis for management algorithms
- In terms of Trauma-specific evidence for goal-directed hemostatic resuscitation, there’s the Da Luz 2014 systematic review
- The purpose was to review the evidence for VHAs in diagnosing early coagulopathies, guiding blood transfusion, and reducing mortality in injured patients
- Looked at observational studies and RCTs
- 55 studies (n = 12,489). 38 prospective cohort. 15 retrospective cohort. 2 before-after. No RCTs.
- Studies investigated TEG/ROTEM for diagnosis of early coagulopathies (n = 40) or for associations with blood-product transfusion (n = 25) or mortality (n = 24).
- Methodologic quality was moderate. Only 3 low risk of bias.
- Most (n = 52) were single-center studies.
- Standard measures of diagnostic accuracy were inconsistently reported.
- Many abnormalities predicted the need for massive transfusion and death, but predictive performance was not consistently superior to routine tests.
- CONCLUSIONS: Limited evidence from observational data suggest that TEG/ROTEM diagnose early trauma coagulopathy and may predict blood-product transfusion and mortality in trauma. Effects on blood-product transfusion, mortality, and other patient-important outcomes remain unproven in randomized trials.
Conservation of Blood Products
In terms of conservation of blood products – which is important from a resource stewardship, cost, and safety standpoint – there are two meta analyses and one systematic review.
- Wikkelsø et al.
- Included 17 trials (n = 1493), most involving cardiac surgery.
- VHA-guided vs standard MTP significantly reduced the proportion transfused with RBCs, FFP, and platelets.
- Conclusion: Transfusion strategies guided by VHAs may reduce the need for blood products in bleeding, but results are mainly based on elective cardiac surgery involving cardiopulmonary bypass, with low-quality evidence.
- Fahrendorff et al. 2017
- Also looked at RCTs. VHA algorithm vs standard. Outcomes were bleeding, transfusion, mortality. 15 RCTs (n = 1238). 9 cardiothoracic, 1 liver transplant, 1 surgical burn wounds, 1 trauma, 1 cirrhotic, 1 PPH.
- Conclusion: The amount of transfused RBCs, FFP, and bleeding volume was found to be significantly reduced in the VHA-guided groups, whereas no significant difference was found for platelet transfusion requirements or mortality.
- Whiting et al. 2014
- RCTs and observational studies. 31 studies. 11 RCTs (n = 1089, 6 TEG, 5 ROTEM).
- Goal: Clinical effectiveness and cost-effectiveness of VHAs in cardiac surgery, trauma-induced coagulopathy, and PPH.
- Conclusion: Reduction in RBC transfusion, platelet transfusion, and FFP transfusion compared with control. Some evidence suggests these algorithms might reduced transfusions, further study is needed to assess patient outcomes
- Clinical outcomes did not differ significantly. No differences b/w TEG/ROTEM.
There is also a 2016 Cochrane review which we will talk about below, but this also found decreased transfusion requirements with VHAs, concluding there is growing evidence to support conservation of blood products.
All in all, there is low quality, mostly cardiac surgery evidence that VHA-guided MTPs reduce transfusion and decreased bleeding.
There are two Cochrane reviews, a meta-analysis that we just went over by Wikkelsø et al., and a Haematology guideline that suggest mortality benefit.
- Cochrane 2011
- The first Cochrane review was in 2011 and concluded there was an absence of evidence that VHAs improve M/M in patients with severe bleeding
- Cochrane 2016 (update)
- The same group revisited the question 5 years later.
- Including only RCTs they found 8 new studies (n = 617) for a total of 17 studies (n = 1493). 6 ongoing trials (unable to get data).
- 15 trials were suitable for meta-analysis.
- Majority = cardiac surgery patients (1435/1493 patients); though there were also liver transplantation, trauma, and orthopedic surgery
- Reduce overall mortality – tendency towards improved mortality outcomes (3.9% vs 7.4%, RR 0.52, 95% CI, 0.28–0.95), though only 8 trials had data (n = 717), 2 being zero event trials. They stated that firm conclusions could not be made due to limitations of study design and power.
- They also found:
- Decreased dialysis dependent renal failure.
- No difference in surgical re-interventions, excessive bleeding events, massive transfusion.
- Low quality evidence based on high risk of bias (only 2 studies were low risk), large heterogeneity, low number of events, imprecision, indirectness.
- TSA indicates 54% information size for mortality.
- Conclusion: There is growing evidence that VHA-guided transfusion may reduce the need for blood products and improve morbidity in patients with bleeding. However, these results are primarily based on trials of elective cardiac surgery involving cardiopulmonary bypass, and the level of evidence remains low. Further evaluation of TEG- or ROTEM-guided transfusion in acute settings and other patient categories in low risk of bias studies is needed.
- Anesthesia Meta-analysis. 2017.
- Same review we just went over for reduction in blood products
- VHA seemed to reduce overall mortality, however, quality of evidence graded as low due to high risk of bias, heterogeneity, imprecision, and low event rate.
- British Society for Haematology Guideline 2018
- Conclusion: based on current evidence = VHA, particularly TEG, may reduce mortality and reduce transfusion exposure and, if available, may be considered for transfusion guidance in trauma haemorrhage. Grade 2B.
- The Bottom line is that: there is low quality evidence, mainly in cardiac surgery, but growing evidence of possible mortality benefit
Several studies are emerging and underway looking into the question of mortality benefit. One that wasn’t included in the Cochrane review was that of Gonzalez et al. from 2016.
- Pragmatic RCT of TEG-guided vs conventional test guided MTP.
- Level 1 trauma center in Denver USA. Patients enrolled during MTP activation.
- The primary outcome was 28-d survival.
- N = 111. IIT.
- Mortality 19.6% (n = 11) vs 36.4% (n = 20). Most deaths w/n 6h.
- Numbers of haemorrhagic deaths lower (8.9% vs. 20%).
- TEG-guided resuscitation = fewer blood products overall, increased ICU- and ventilator-free days.
- Conclusion: Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by SLTs and utilizes less plasma and platelet transfusions during the early phase of resuscitation
- This study provides evidence that VHA‐guided transfusion may be beneficial for the management of acute bleeding in trauma, over and above the effects of the empiric 1:1:1 transfusion.
- The Implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy Trial (iTACTIC) aims to recruit 400 patients across Europe, randomizing them to a TEG-guided or CCT-guided resuscitation
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