Functional fibrinogen (FLEV-TEG) versus the Clauss method in an obstetric population: a comparative study

Abstract

Background: Hemostasis is the dynamic equilibrium between coagulation and fibrinolysis. During pregnancy, the balance shifts toward a hypercoagulative state; however placental abruption and abnormal placentations may lead to rapidly evolving coagulopathy characterized by the increased activation of procoagulant pathways. These processes can result in hypofibrinogenemia, with fibrinogen levels dropping to 2 g/L or less and an associated increased risk of post-partum hemorrhage. The aim of the present study was to evaluate the concordance between two methods of functional fibrinogen measurement: the Thromboelastography (TEG) method (also known as FLEV) vs. the Clauss method. Three patient groups were considered: healthy volunteers; non-pathological pregnant patients; and pregnant patients who went on to develop postpartum hemorrhage. Methods: A prospective observational study. Inclusion criteria were: healthy volunteer women of childbearing age, non-pathological pregnant women at term, and pregnant hemorrhagic patients subjected to elective or urgent caesarean section (CS), with blood loss exceeding 1000 mL. Exclusion criteria were age < 18 years, a history of coagulopathy, and treatment with contraceptives, anticoagulants, or antiplatelet agents. Results: Bland-Altman plots showed a significant overestimation with the FLEV method in all three patient groups: bias was − 133.36 mg/dL for healthy volunteers (95% IC: − 257.84; − 8.88. Critical difference: 124.48); − 56.30 mg/dL for healthy pregnant patients (95% IC: − 225.53; 112.93. Critical difference: 169.23); and − 159.05 mg/dL for hemorrhagic pregnant patients (95% IC: − 333.24; 15.148. Critical difference: 174.19). Regression analyses detected a linear correlation between FLEV and Clauss for healthy volunteers, healthy pregnant patients, and hemorrhagic pregnant patients (R 2 0.27, p value = 0.002; R 2 0.31, p value = 0.001; R 2 0.35, p value = 0.001, respectively). ANOVA revealed a statistically significant difference in fibrinogen concentration between all three patients groups when assayed using the Clauss method (p value < 0.001 for all the comparisons), but no statistically significant difference between the two patients groups of pregnant women when using the FLEV method. Conclusions: The FLEV method does not provide a valid alternative to the Clauss method due to the problem of fibrinogen overestimation, and for this reason it should not be recommended for the evaluation of patients with an increased risk of hypofibrinogenemia.

Systematic review of viscoelastic testing (TEG/ROTEM) in obstetrics and recommendations from the women's SSC of the ISTH

“…61,62 Studies have shown that TEG can rapidly detect changes in hemostasis, which is advantageous in the context of ongoing hemorrhage, but standard laboratory assays such as prothrombin time and activated partial thromboplastin time detected greater differences that correlated better with estimated blood loss. 63 Katz et al and Spasiano et al 64,65 compared the TEG method of measuring functional fibrinogen levels (FLEV) to the Clauss method, and reported that TEG-FLEV overestimates fibrinogen levels, which may lead to undertreatment or a delay in treatment. TEG has also been used to study coagulation changes in placental abruption, but further studies in this area are needed.…”

Viscoelastic haemostatic point‐of‐care assays in the management of postpartum haemorrhage: a narrative review

“…A further study including 34 healthy pregnant patients and 32 haemorrhaging pregnant patients suggested no significant differences in TEG maximum amplitude and functional fibrinogen maximum amplitude between these groups and that the TEG functional fibrinogen measurement overestimated the fibrinogen concentration in comparison with the Clauss method [66]. Sample sizes for both of the above studies, particularly of patients with PPH, were small and further data are required to confirm these findings.…”

Blood management in post-partum haemorrhage, including point of care coagulation tests

“…This study used a TEG reagent that is designed to look at the intrinsic clotting pathway rather than isolate fibrinogen contribution to clot formation [42]. Recent studies looking at FLEV-TEG, designed to measure the contribution of fibrinogen, have raised concerns that it may overestimate fibrinogen levels and if used as a transfusion guide could lead to under treatment [43,44]. Small studies have described the benefit of using TEG in PPH [33,45] and TEG algorithms have been published based on normal values gained from healthy pregnant women [46].…”