For some time now thromboelastography (TEG) and related viscoelastic tests have been the darlings of the FOAM world. I must admit, even I have been seduced by their elegant and holistic perspective of the coagulation system. And yet despite their clinical potential and widespread patronage, few studies have examined how the use of TEG to manipulate the potency of coagulation affects clinical outcomes.
A recent article by Conelly et al, published in JAMA Surgery examined the efficacy of a TEG-guided approach to venous thromboembolism (VTE) prophylactic enoxaparin dosing (1). These authors enrolled 185 patients at three tertiary medical centers, the majority of which were admitted to the trauma service, and randomized them to either the standard 30 mg twice daily empiric dosing strategy, or a TEG guided approach. Patients randomized to the TEG guided approach received the standard BID dosing until a steady state was achieved (4-6 hours after the third dose). After which a TEG was performed and the enoxaparin dose was adjusted based on the delta-R (the difference in time to initial fibrin formation in minutes between standard and heparinase TEG assays). Following adjustment, 3 additional doses were given and a further TEG was drawn. This pattern was repeated until an delta-R greater than 1-minute was achieved.
The overall rate of VTE was far lower than expected (6.5%). Having powered their study for a VTE rate of 20%, the authors stopped the trial early, stating that at the current rate of VTE they would require 3212 patients to demonstrate a clinically important difference. Despite this potential for type-II error, the rates in VTE between the groups was essentially identical. The authors found no significant difference in their primary outcome, the rate of VTE during hospital admission, 6.7% and 6.3% in the control and TEG-guided groups respectively. And while the rate of bleeding was not statistically different (p=0.08), the point estimate observed in the TEG-guided approach, was certainly concerning (5.6% vs 13.5%).
Now these failures may not entirely be the fault of viscoelastic testing, but rather our unfamiliarity with the ideal method to prevent VTEs in patients resistant to low-molecular weight heparin prophylaxis. While patients randomized to the TEG-guided approach received a higher median dose than the control group (37.5 mg vs 30 mg) the overall change in delta-R varied very little between the groups. In fact, only 22 (11.9%) patients achieved delta-R greater than 1-minute, which were essentially distributed equally between the two groups (13.5% vs 10.4%). 32.6% and 33.3% of the control and TEG-guided groups were found to have anti-factor Xa levels below the recommended level of inhibition (<0.20 IU/mL). Previous data suggests an anti-Xa driven protocol may be a more efficacious target if a goal directed strategy is utilized (2). Or perhaps we have reach the point of diminishing returns. That the risk of bleeding outweighs any small incremental benefits gained from these more aggressive prophylactic strategies.
I certainly do not claim to be an expert in the coagulation cascade. Nor do I contend to be anything more than an enthusiastic novice when it comes to the interpretation of viscoelastic testing, but this article certainly highlights how the unquestionable use of any test can drive us to unnecessary and potentially harmful interventions. It suggests we cannot just empirically apply viscoelastic testing to all clinical situations without truly understanding how its application may influence clinical decision and affect clinical outcomes.
- Connelly CR, Van PY, Hart KD, et al. Thrombelastography-Based Dosing of Enoxaparin for Thromboprophylaxis in Trauma and Surgical Patients: A Randomized Clinical Trial. JAMA Surg. 2016;:e162069.
- Ko A, Harada MY, Barmparas G, et al. Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma. JAMA Surg. 2016;
-Special thanks to @bloodman for putting this study and all things coagulative in their proper perspective