Viscoelastic-based determination of fibrinogen concentration

Trials and tribulations of viscoelastic-based determination of fibrinogen concentration

Ranucci M, Di Dida U, Baryshnikova E. Anesth Analg. 2020;130(3):644–53. DOI: 10.1213/ANE.0000000000004522

Acquired fibrinogen deficiency is an important contributor to severe bleeding in a number of clinical scenarios – for example, cardiac surgery, trauma, postpartum haemorrhage, and liver surgery and transplantation.

Current guidelines for cardiac surgery, major noncardiac surgery, and trauma suggest clinicians consider fibrinogen supplementation (with fibrinogen concentrate or cryoprecipitate) in a bleeding patient with fibrinogen levels <1.5 g/L (Kozek-Langenecker et al., 2017; Pagano et al., 2018; Raphael et al., 2019; Rossaint et al., 2016).

The guidelines also suggest applying viscoelastic tests (VETs) for fibrinogen contribution to clot formation to rapidly determine functional fibrinogen levels for prompt treatment, but only one of the guidelines (Raphael et al., 2019) suggests a VET-based cut-off value.

Problems arise in translating the results from VETs, which are measured in whole blood, into corresponding plasma fibrinogen concentration values derived from the ‘gold-standard’ Clauss assay. Variability in the Clauss assay and the variety of VETs on the market (based on different technologies, activators and platelet inhibitors) make comparisons difficult.

The authors of this narrative review examined the available evidence on VETs and translation of test

results into fibrinogen concentrations with a view to developing reliable conversion factors (Figure 1).

Figure 1. Assays for functional fibrinogen: How do they relate?

What were the viscoelastic tests examined?

The main types of VETs examined measure:

• Functional fibrinogen (FF) with thromboelastography (TEG)
• Fibrinogen contribution to clot firmness (FIBTEM fibrinogen determination) with rotational thromboelastometry (ROTEM)
• Fibrinogen contribution to clot strength (FCS) with sonorheometry (Quantra)

Can the viscoelastic tests predict Clauss fibrinogen values?

TEG-based fibrinogen contribution to clot firmness

• No studies on predictive value for 1.5 g/L cut-off of Clauss fibrinogen test
• Values ~12 mm clot amplitude and 200 mg/dL FF from pooled studies, but large variation in experimental points
• Appears to overestimate FF

ROTEM-based fibrinogen contribution to clot firmness

• Most studied test type
• Measures maximum clot firmness in millimetres (MCF)
• Best predictor of a Clauss fibrinogen <1.5 g/L: equivalent to MCF ~8 mm
• Can also measure clot firmness at 5 (A5) and 10 (A10) minutes after clot initiation for more rapid result (A10 of ~8 mm best for comparison)

Quantra-based fibrinogen contribution to clot firmness

• Uses ultrasound to measure functional clot strength (FCS)
• Expressed as shear modulus (in hPa), which has linear relationship to amplitude (mm) measures of clot stiffness in clinical fibrinogen range
• Clinical experience limited and data inconsistent
• Overall correlation of FCS to Clauss fibrinogen is moderate to very good, but large between-study variability when searching for meaningful cut-off points

What conclusions can we draw for practice?

1. Statistically, results from VETs correlate well with the Clauss assay, but within-test and between-test results vary too much to develop reliable conversion factors.
2. Because VETs can dynamically assess fibrinogen levels, they are probably best used to monitor ongoing bleeding and fibrinogen supplementation, rather than identifying specific cut-off levels for initiating treatment.
3. When using VETs for decision-making, clinicians should consider the possible problems and associated sources of bias (Table 1).

Table 1. Factors affecting VET-based tests: implications for practice. A5, A10, value of clot firmness 5, 10 minutes after clot initiation; Clauss, Clauss assay for fibrinogen concentration; FXIII, factor XIII; MCF, maximum clot firmness; NA, not applicable; NPV, negative predictive value; PPV, positive predictive value; ROTEM-FIBTEM, rotational thromboelastometry fibrinogen determination; VET, viscoelastic test.

More on viscoelastic tests for assessing fibrinogen contribution to clot formation.

References

Kozek-Langenecker SA, Ahmed AB, Afshari A, Albaladejo P, Aldecoa C, Barauskas G, et al. Management of severe perioperative bleeding: guidelines from the European Society of Anaesthesiology: First update 2016. Eur J Anaesthesiol. 2017;34:332–95.

Pagano D, Milojevic M, Meesters MI, Benedetto U, Bolliger D, von Heymann C, et al. 2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery. Eur J Cardiothorac Surg. 2018;53:79–111.

Raphael J, Mazer CD, Subramani S, Schroeder A, Abdalla M, Ferreira R, et al. Society of Cardiovascular Anesthesiologists (SCA) Clinical Practice Improvement (CPI) advisory for management of perioperative bleeding and hemostasis in cardiac surgery patients. J Cardiothorac Vasc Anesth. 2019;33:2887–2899.

Rossaint R, Bouillon B, Cerny V, Coats TJ, Duranteau J, Fernández-Mondéjar E, et al. The European guideline on management of major bleeding and coagulopathy following trauma: fourth edition. Crit Care. 2016;20:100.